Last data update: Jan 27, 2025. (Total: 48650 publications since 2009)
Records 1-30 (of 41 Records) |
Query Trace: Retchless AC[original query] |
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Epidemiologic and genomic evidence for zoonotic transmission of SARS-CoV-2 among people and animals on a Michigan mink farm, United States, 2020
Ghai RR , Straily A , Wineland N , Calogero J , Stobierski MG , Signs K , Blievernicht M , Torres-Mendoza Y , Waltenburg MA , Condrey JA , Blankenship HM , Riner D , Barr N , Schalow M , Goodrich J , Collins C , Ahmad A , Metz JM , Herzegh O , Straka K , Arsnoe DM , Duffiney AG , Shriner SA , Kainulainen MH , Carpenter A , Whitehill F , Wendling NM , Stoddard RA , Retchless AC , Uehara A , Tao Y , Li Y , Zhang J , Tong S , Barton Behravesh C . Viruses 2023 15 (12) ![]() ![]() Farmed mink are one of few animals in which infection with SARS-CoV-2 has resulted in sustained transmission among a population and spillback from mink to people. In September 2020, mink on a Michigan farm exhibited increased morbidity and mortality rates due to confirmed SARS-CoV-2 infection. We conducted an epidemiologic investigation to identify the source of initial mink exposure, assess the degree of spread within the facility's overall mink population, and evaluate the risk of further viral spread on the farm and in surrounding wildlife habitats. Three farm employees reported symptoms consistent with COVID-19 the same day that increased mortality rates were observed among the mink herd. One of these individuals, and another asymptomatic employee, tested positive for SARS-CoV-2 by real-time reverse transcription PCR (RT-qPCR) 9 days later. All but one mink sampled on the farm were positive for SARS-CoV-2 based on nucleic acid detection from at least one oral, nasal, or rectal swab tested by RT-qPCR (99%). Sequence analysis showed high degrees of similarity between sequences from mink and the two positive farm employees. Epidemiologic and genomic data, including the presence of F486L and N501T mutations believed to arise through mink adaptation, support the hypothesis that the two employees with SARS-CoV-2 nucleic acid detection contracted COVID-19 from mink. However, the specific source of virus introduction onto the farm was not identified. Three companion animals living with mink farm employees and 31 wild animals of six species sampled in the surrounding area were negative for SARS-CoV-2 by RT-qPCR. Results from this investigation support the necessity of a One Health approach to manage the zoonotic spread of SARS-CoV-2 and underscores the critical need for multifaceted public health approaches to prevent the introduction and spread of respiratory viruses on mink farms. |
One Health Investigation of SARS-CoV-2 in People and Animals on Multiple Mink Farms in Utah.
Cossaboom CM , Wendling NM , Lewis NM , Rettler H , Harvey RR , Amman BR , Towner JS , Spengler JR , Erickson R , Burnett C , Young EL , Oakeson K , Carpenter A , Kainulainen MH , Chatterjee P , Flint M , Uehara A , Li Y , Zhang J , Kelleher A , Lynch B , Retchless AC , Tong S , Ahmad A , Bunkley P , Godino C , Herzegh O , Drobeniuc J , Rooney J , Taylor D , Barton Behravesh C . Viruses 2022 15 (1) ![]() ![]() From July-November 2020, mink (Neogale vison) on 12 Utah farms experienced an increase in mortality rates due to confirmed SARS-CoV-2 infection. We conducted epidemiologic investigations on six farms to identify the source of virus introduction, track cross-species transmission, and assess viral evolution. Interviews were conducted and specimens were collected from persons living or working on participating farms and from multiple animal species. Swabs and sera were tested by SARS-CoV-2 real-time reverse transcription polymerase chain reaction (rRT-PCR) and serological assays, respectively. Whole genome sequencing was attempted for specimens with cycle threshold values <30. Evidence of SARS-CoV-2 infection was detected by rRT-PCR or serology in ≥1 person, farmed mink, dog, and/or feral cat on each farm. Sequence analysis showed high similarity between mink and human sequences on corresponding farms. On farms sampled at multiple time points, mink tested rRT-PCR positive up to 16 weeks post-onset of increased mortality. Workers likely introduced SARS-CoV-2 to mink, and mink transmitted SARS-CoV-2 to other animal species; mink-to-human transmission was not identified. Our findings provide critical evidence to support interventions to prevent and manage SARS-CoV-2 in people and animals on mink farms and emphasizes the importance of a One Health approach to address emerging zoonoses. |
Benchmark datasets for SARS-CoV-2 surveillance bioinformatics.
Xiaoli L , Hagey JV , Park DJ , Gulvik CA , Young EL , Alikhan NF , Lawsin A , Hassell N , Knipe K , Oakeson KF , Retchless AC , Shakya M , Lo CC , Chain P , Page AJ , Metcalf BJ , Su M , Rowell J , Vidyaprakash E , Paden CR , Huang AD , Roellig D , Patel K , Winglee K , Weigand MR , Katz LS . PeerJ 2022 10 e13821 ![]() ![]() BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), has spread globally and is being surveilled with an international genome sequencing effort. Surveillance consists of sample acquisition, library preparation, and whole genome sequencing. This has necessitated a classification scheme detailing Variants of Concern (VOC) and Variants of Interest (VOI), and the rapid expansion of bioinformatics tools for sequence analysis. These bioinformatic tools are means for major actionable results: maintaining quality assurance and checks, defining population structure, performing genomic epidemiology, and inferring lineage to allow reliable and actionable identification and classification. Additionally, the pandemic has required public health laboratories to reach high throughput proficiency in sequencing library preparation and downstream data analysis rapidly. However, both processes can be limited by a lack of a standardized sequence dataset. METHODS: We identified six SARS-CoV-2 sequence datasets from recent publications, public databases and internal resources. In addition, we created a method to mine public databases to identify representative genomes for these datasets. Using this novel method, we identified several genomes as either VOI/VOC representatives or non-VOI/VOC representatives. To describe each dataset, we utilized a previously published datasets format, which describes accession information and whole dataset information. Additionally, a script from the same publication has been enhanced to download and verify all data from this study. RESULTS: The benchmark datasets focus on the two most widely used sequencing platforms: long read sequencing data from the Oxford Nanopore Technologies platform and short read sequencing data from the Illumina platform. There are six datasets: three were derived from recent publications; two were derived from data mining public databases to answer common questions not covered by published datasets; one unique dataset representing common sequence failures was obtained by rigorously scrutinizing data that did not pass quality checks. The dataset summary table, data mining script and quality control (QC) values for all sequence data are publicly available on GitHub: https://github.com/CDCgov/datasets-sars-cov-2. DISCUSSION: The datasets presented here were generated to help public health laboratories build sequencing and bioinformatics capacity, benchmark different workflows and pipelines, and calibrate QC thresholds to ensure sequencing quality. Together, improvements in these areas support accurate and timely outbreak investigation and surveillance, providing actionable data for pandemic management. Furthermore, these publicly available and standardized benchmark data will facilitate the development and adjudication of new pipelines. |
Invasive meningococcal disease among people experiencing homelessness-United States, 2016-2019
Rudmann KC , Brown NE , Blain A , Burns M , Ramsey A , Las Nueces D , Martin T , Barnes M , Davizon ES , Retchless AC , Potts C , Wang X , Hariri S , McNamara LA . J Infect Dis 2022 226 S322-S326 BACKGROUND: Recently, several invasive meningococcal disease (IMD) outbreaks caused by Neisseria meningitidis have occurred among people experiencing homelessness (PEH). However, overall IMD risk among PEH is not well described. We compared incidence and characteristics of IMD among PEH and persons not known to be experiencing homelessness (non-PEH) in the United States. METHODS: We analyzed 2016-2019 IMD data from the National Notifiable Diseases Surveillance System (NNDSS) and enhanced meningococcal disease surveillance. Incidence was calculated using U.S. census data and Point-in-Time counts from the U.S. Department of Housing and Urban Development. RESULTS: Of cases from states participating in enhanced surveillance during 2016-2019 (n = 1409), 45 (3.2%) cases occurred among PEH. Annual incidence was higher among PEH (2.12 cases/100,000) than non-PEH (0.11 cases/100,000; relative risk: 19.8, 95% CI: 14.8-26.7). Excluding outbreak-associated cases (PEH n = 18, 40%; non-PEH n = 98, 7.2%), incidence among PEH remained elevated compared to incidence in non-PEH (relative risk: 12.8, 95% CI: 8.8-18.8). Serogroup C was identified in 68.2% of PEH cases compared to 26.4% in non-PEH (p < 0.0001). CONCLUSIONS: PEH are at increased risk for IMD. Further assessment is needed to determine the feasibility and potential impact of meningococcal vaccination for PEH in the United States. |
Antimicrobial Susceptibility Survey of Invasive Haemophilus influenzae in the United States in 2016.
Potts CC , Rodriguez-Rivera LD , Retchless AC , Buono SA , Chen AT , Marjuki H , Blain AE , Wang X . Microbiol Spectr 2022 10 (3) e0257921 ![]() Antibiotics are important for the treatment and prevention of invasive Haemophilus influenzae disease. Reduced susceptibility to clinically relevant drugs, except ampicillin, has been uncommon in the United States. Susceptibility of 700 invasive H. influenzae isolates, collected through population-based surveillance during 2016, was assessed for 15 antibiotics using broth microdilution, according to the CLSI guidelines; a subset of 104 isolates were also assessed for rifampin susceptibility using Etest. Genomes were sequenced to identify genes and mutations known to be associated with reduced susceptibility to clinically relevant drugs. A total of 508 (72.6%) had reduced susceptibility to at least one antibiotic and more than half of the isolates exhibited reduced susceptibility to only one (33.6%) or two (21.6%) antibiotic classes. All tested isolates were susceptible to rifampin, a chemoprophylaxis agent, and <1% (n=3) of isolates had reduced susceptibility to third generation cephalosporins, which are recommended for invasive disease treatment. In contrast, ampicillin resistance was more common (28.1%) and predominantly associated with the detection of a -lactamase gene; 26.2% of isolates in the collection contained either a TEM-1 or ROB-1 -lactamase gene, including 88.8% of ampicillin-resistant isolates. -lactamase negative ampicillin-resistant (BLNAR) isolates were less common and associated with ftsI mutations; resistance to amoxicillin-clavulanate was detected in <2% (n=13) of isolates. The proportion of reduced susceptibility observed was higher among nontypeable H. influenzae and serotype e than other serotypes. US invasive H. influenzae isolates remain predominantly susceptible to clinically relevant antibiotics except ampicillin, and BLNAR isolates remain uncommon. IMPORTANCE Antibiotics play an important role for the treatment and prevention of invasive Haemophilus influenzae disease. Antimicrobial resistance survey of invasive H. influenzae isolates collected in 2016 showed that the US H. influenzae population remained susceptible to clinically relevant antibiotics, except for ampicillin. Detection of approximately a quarter ampicillin-resistant and -lactamase containing strains demonstrates that resistance mechanisms can be acquired and sustained within the H. influenzae population, highlighting the continued importance of antimicrobial resistance surveillance for H. influenzae to monitor susceptibility trends and mechanisms of resistance. |
Household Transmission and Symptomology of SARS-CoV-2 Alpha Variant Among Children-California and Colorado, 2021.
Waltenburg MA , Whaley MJ , Chancey RJ , Donnelly MAP , Chuey MR , Soto R , Schwartz NG , Chu VT , Sleweon S , McCormick DW , Uehara A , Retchless AC , Tong S , Folster JM , Petway M , Thornburg NJ , Drobeniuc J , Austin B , Hudziec MM , Stringer G , Albanese BA , Totten SE , Matzinger SR , Staples JE , Killerby ME , Hughes LJ , Matanock A , Beatty M , Tate JE , Kirking HL , Hsu CH . J Pediatr 2022 247 29-37 e7 ![]() OBJECTIVE: To assess the household secondary infection risk (SIR) of B.1.1.7 (Alpha) and non-Alpha lineages of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among children. STUDY DESIGN: During January-April 2021, we prospectively followed households with a SARS-CoV-2 infection. We collected questionnaires, serial nasopharyngeal swabs for RT-PCR testing and whole genome sequencing, and serial blood samples for serology testing. We calculated SIRs by primary case age (pediatric vs. adult), household contact age, and viral lineage. We evaluated risk factors associated with transmission and described symptom profiles among children. RESULTS: Among 36 households with pediatric primary cases, 21 (58%) had secondary infections. Among 91 households with adult primary cases, 51 (56%) had secondary infections. SIRs among pediatric and adult primary cases were 45% and 54%, respectively (OR: 0.79 [95% CI 0.41-1.54]). SIRs among pediatric primary cases with Alpha and non-Alpha lineage were 55% and 46%, respectively (OR: 1.52 [CI 0.51-4.53]). SIRs among pediatric and adult household contacts were 55% and 49%, respectively (OR: 1.01 [CI 0.68-1.50]). Among pediatric contacts, no significant differences in odds of acquiring infection by demographic or household characteristics were observed. CONCLUSIONS: Household transmission of SARS-CoV-2 from children and adult primary cases to household members was frequent. Risk of secondary infection was similar among child and adult household contacts. Among children, household transmission of SARS-CoV-2 and risk of secondary infection was not influenced by lineage. Continued mitigation strategies (e.g., masking, physical distancing, vaccination) are needed to protect at-risk groups regardless of virus lineage circulating in communities. |
Transmission of SARS-CoV-2 Delta variant (B.1.617.2) from a fully vaccinated human to a canine in Georgia, July 2021.
Wendling NM , Carpenter A , Liew A , Ghai RR , Gallardo-Romero N , Stoddard RA , Tao Y , Zhang J , Retchless AC , Ahmad A , Bunkley P , Godino C , Mauldin MR , Varela K , Ritter JM , Hennebelle J , Feldpausch A , Gabel J , Kainulainen MH , Herzegh O , Tong S , Spengler JR , Barton Behravesh C . Zoonoses Public Health 2022 69 (5) 587-592 ![]() SARS-CoV-2 infection has been described in a wide range of species, including domestic animals such as dogs and cats. Illness in dogs is usually self-limiting, and further diagnostics may not be pursued if clinical signs resolve or they respond to empirical treatment. As new variants emerge, the clinical presentation and role in transmission may vary in animals. This report highlights different clinical presentations and immunological responses in two SARS-CoV-2 Delta-variant-positive dogs with similar exposure to the same fully vaccinated human with a SARS-CoV-2 infection and emphasizes the need for active surveillance and additional One Health research on SARS-CoV-2 variant infections in companion animals and other species. |
Risk factors for invasive meningococcal disease belonging to a novel urethritis clade of Neisseria meningitidis-United States, 2013-2017
Oliver SE , Retchless AC , Blain AE , McNamara LA , Ahrabifard S , Farley M , Weiss D , Zaremski E , Wang X , Hariri S . Open Forum Infect Dis 2022 9 (4) ofac035 We describe cases of invasive meningococcal disease caused by nongroupable Neisseria meningitidis belonging to a novel phylogenetic clade associated with urethritis. Seven cases were identified, comprising 0.6% of sequenced invasive meningococcal disease isolates from 2013 to 2017. Five patients had a known or likely immunocompromising condition, including 2 with a complement deficiency. |
Antimicrobial Susceptibility Survey of Invasive Neisseria meningitidis, United States 2012-2016.
Potts CC , Rodriguez-Rivera LD , Retchless AC , Hu F , Marjuki H , Blain AE , McNamara LA , Wang X . J Infect Dis 2022 225 (11) 1871-1875 ![]() ![]() BACKGROUND: Historically, antimicrobial resistance has been rare in US invasive meningococcal disease cases. METHODS: Meningococcal isolates (n=695) were collected through population-based surveillance, 2012-2016, and national surveillance, 2015-2016. Antimicrobial susceptibility was assessed by broth microdilution. Resistance mechanisms were characterized using whole genome sequencing. RESULTS: All isolates were susceptible to six antibiotics (cefotaxime, ceftriaxone, meropenem, rifampin, minocycline, and azithromycin). Approximately 25% were penicillin- or ampicillin-intermediate; among these, 79% contained mosaic penA gene mutations. Less than 1% of isolates were penicillin-, ampicillin-, ciprofloxacin-, or levofloxacin-resistant. CONCLUSION: Penicillin- and ampicillin-intermediate isolates were common, but resistance to clinically relevant antibiotics remained rare. |
Genomic Insights on Variation Underlying Capsule Expression in Meningococcal Carriage Isolates From University Students, United States, 2015-2016.
Whaley MJ , Vuong JT , Topaz N , Chang HY , Thomas JD , Jenkins LT , Hu F , Schmink S , Steward-Clark E , Mathis M , Rodriguez-Rivera LD , Retchless AC , Joseph SJ , Chen A , Acosta AM , McNamara L , Soeters HM , Mbaeyi S , Marjuki H , Wang X . Front Microbiol 2022 13 815044 ![]() ![]() In January and February 2015, Neisseria meningitidis serogroup B (NmB) outbreaks occurred at two universities in the United States, and mass vaccination campaigns using MenB vaccines were initiated as part of a public health response. Meningococcal carriage evaluations were conducted concurrently with vaccination campaigns at these two universities and at a third university, where no NmB outbreak occurred. Meningococcal isolates (N = 1,514) obtained from these evaluations were characterized for capsule biosynthesis by whole-genome sequencing (WGS). Functional capsule polysaccharide synthesis (cps) loci belonging to one of seven capsule genogroups (B, C, E, W, X, Y, and Z) were identified in 122 isolates (8.1%). Approximately half [732 (48.4%)] of isolates could not be genogrouped because of the lack of any serogroup-specific genes. The remaining 660 isolates (43.5%) contained serogroup-specific genes for genogroup B, C, E, W, X, Y, or Z, but had mutations in the cps loci. Identified mutations included frameshift or point mutations resulting in premature stop codons, missing or fragmented genes, or disruptions due to insertion elements. Despite these mutations, 49/660 isolates expressed capsule as observed with slide agglutination, whereas 45/122 isolates with functional cps loci did not express capsule. Neither the variable capsule expression nor the genetic variation in the cps locus was limited to a certain clonal complex, except for capsule null isolates (predominantly clonal complex 198). Most of the meningococcal carriage isolates collected from student populations at three US universities were non-groupable as a result of either being capsule null or containing mutations within the capsule locus. Several mutations inhibiting expression of the genes involved with the synthesis and transport of the capsule may be reversible, allowing the bacteria to switch between an encapsulated and non-encapsulated state. These findings are particularly important as carriage is an important component of the transmission cycle of the pathogen, and understanding the impact of genetic variations on the synthesis of capsule, a meningococcal vaccine target and an important virulence factor, may ultimately inform strategies for control and prevention of disease caused by this pathogen. |
Investigation of SARS-CoV-2 Transmission Associated With a Large Indoor Convention - New York City, November-December 2021.
Sami S , Horter L , Valencia D , Thomas I , Pomeroy M , Walker B , Smith-Jeffcoat SE , Tate JE , Kirking HL , Kyaw NTT , Burns R , Blaney K , Dorabawila V , Hoen R , Zirnhelt Z , Schardin C , Uehara A , Retchless AC , Brown VR , Gebru Y , Powell C , Bart SM , Vostok J , Lund H , Kaess J , Gumke M , Propper R , Thomas D , Ojo M , Green A , Wieck M , Wilson E , Hollingshead RJ , Nunez SV , Saady DM , Porse CC , Gardner K , Drociuk D , Scott J , Perez T , Collins J , Shaffner J , Pray I , Rust LT , Brady S , Kerins JL , Teran RA , Hughes V , Sepcic V , Low EW , Kemble SK , Berkley A , Cleavinger K , Safi H , Webb LM , Hutton S , Dewart C , Dickerson K , Hawkins E , Zafar J , Krueger A , Bushman D , Ethridge B , Hansen K , Tant J , Reed C , Boutwell C , Hanson J , Gillespie M , Donahue M , Lane P , Serrano R , Hernandez L , Dethloff MA , Lynfield R , Como-Sabetti K , Lutterloh E , Ackelsberg J , Ricaldi JN . MMWR Morb Mortal Wkly Rep 2022 71 (7) 243-248 During November 19-21, 2021, an indoor convention (event) in New York City (NYC), was attended by approximately 53,000 persons from 52 U.S. jurisdictions and 30 foreign countries. In-person registration for the event began on November 18, 2021. The venue was equipped with high efficiency particulate air (HEPA) filtration, and attendees were required to wear a mask indoors and have documented receipt of at least 1 dose of a COVID-19 vaccine.* On December 2, 2021, the Minnesota Department of Health reported the first case of community-acquired COVID-19 in the United States caused by the SARS-CoV-2 B.1.1.529 (Omicron) variant in a person who had attended the event (1). CDC collaborated with state and local health departments to assess event-associated COVID-19 cases and potential exposures among U.S.-based attendees using data from COVID-19 surveillance systems and an anonymous online attendee survey. Among 34,541 attendees with available contact information, surveillance data identified test results for 4,560, including 119 (2.6%) persons from 16 jurisdictions with positive SARS-CoV-2 test results. Most (4,041 [95.2%]), survey respondents reported always wearing a mask while indoors at the event. Compared with test-negative respondents, test-positive respondents were more likely to report attending bars, karaoke, or nightclubs, and eating or drinking indoors near others for at least 15 minutes. Among 4,560 attendees who received testing, evidence of widespread transmission during the event was not identified. Genomic sequencing of 20 specimens identified the SARS-CoV-2 B.1.617.2 (Delta) variant (AY.25 and AY.103 sublineages) in 15 (75%) cases, and the Omicron variant (BA.1 sublineage) in five (25%) cases. These findings reinforce the importance of implementing multiple, simultaneous prevention measures, such as ensuring up-to-date vaccination, mask use, physical distancing, and improved ventilation in limiting SARS-CoV-2 transmission, during large, indoor events.(†). |
Household transmission of SARS-CoV-2 Alpha variant - United States, 2021.
Donnelly MAP , Chuey MR , Soto R , Schwartz NG , Chu VT , Konkle SL , Sleweon S , Ruffin J , Haberling DL , Guagliardo SAJ , Stoddard RA , Anderson RD , Morgan CN , Rossetti R , McCormick DW , Magleby R , Sheldon SW , Dietrich EA , Uehara A , Retchless AC , Tong S , Folster JM , Drobeniuc J , Petway ME , Austin B , Stous S , McDonald E , Jain S , Hudziec MM , Stringer G , Albanese BA , Totten SE , Staples JE , Killerby ME , Hughes L , Matanock A , Beatty M , Tate JE , Kirking HL , Hsu CH . Clin Infect Dis 2022 75 (1) e122-e132 ![]() ![]() BACKGROUND: In Spring 2021, SARS-CoV-2 B.1.1.7 (Alpha) became the predominant variant in the U.S. Research suggests that Alpha has increased transmissibility compared to non-Alpha lineages. We estimated household secondary infection risk (SIR), assessed characteristics associated with transmission, and compared symptoms of persons with Alpha and non-Alpha infections. METHODS: We followed households with SARS-CoV-2 infection for two weeks in San Diego County and metropolitan Denver, January to April 2021. We collected epidemiologic information and biospecimens for serology, RT-PCR, and whole genome sequencing. We stratified SIR and symptoms by lineage, and identified characteristics associated with transmission using Generalized Estimating Equations. RESULTS: We investigated 127 households with 322 household contacts; 72 households (56.7%) had member(s) with secondary infections. SIRs were not significantly higher for Alpha (61.0% [95% confidence interval (CI) 52.4-69.0%]) than non-Alpha (55.6% [CI 44.7-65.9%], P = 0.49). In households with Alpha, persons who identified as Asian or Hispanic/Latino had significantly higher SIRs than those who identified as White (P = 0.01 and 0.03, respectively). Close contact (e.g., kissing, hugging) with primary cases was associated with increased transmission for all lineages. Persons with Alpha infection were more likely to report constitutional symptoms than persons with non-Alpha (86.9% vs. 76.8%, P = 0.05). CONCLUSIONS: Household SIRs were similar for Alpha and non-Alpha. Comparable SIRs may be due to saturation of transmission risk in households owing to extensive close contact, or true lack of difference in transmission rates. Avoiding close contact within households may reduce SARS-CoV-2 transmission for all lineages among household members. |
Evaluation of urethrotropic clade meningococcal infection by urine metagenomic shotgun sequencing.
Retchless AC , Itsko M , Bazan JA , Norris Turner A , Hu F , Joseph SJ , Carter A , Brown M , Snyder B , Wang X . J Clin Microbiol 2021 60 (2) Jcm0173221 ![]() ![]() Background Urethral infections caused by an emerging nongroupable (NG) urethrotropic clade of Neisseria meningitidis (Nm) were first reported in the United States in 2015 (the "U.S. NmNG urethritis clade"). Here we evaluate for the presence of other urethral pathogens in men with U.S. NmNG urethritis clade infection. Methods: We evaluated 129 urine specimens collected from men at a sexual health clinic, including 33 from patients with culture-confirmed or suspected urethral Nm infection and 96 specimens in which nucleic acid amplification test detected Neisseria gonorrhoeae (Ng), Chlamydia trachomatis (Ct), both pathogens, or neither pathogen. Nm was detected first by real-time PCR, followed by metagenomic shotgun sequencing of 91 specimens to identify coinfections. Nm genomes were sequenced following selective whole genome amplification when possible. Results: Metagenomic sequencing detected Nm in 16 of 17 specimens from culture-confirmed Nm cases, with no coinfection by other conventional urethral pathogens. Metagenomic sequencing also detected Nm in three Ct positive specimens, one specimen positive for both Ng and Ct, and nine specimens with negative Ng and Ct results, eight of which had suspected Neisseria infections. Nm from culture-confirmed Nm cases belonged to the U.S. NmNG urethritis clade, while Nm identified in other specimens belonged to multiple clonal complexes. Additional urethral pathogens were predominant in non-Nm specimens, including Ng, Ct, Mycoplasma genitalium, Ureaplasma urealyticum, and herpes simplex virus type-2. Conclusions: Coinfection with other conventional urethral pathogens is rare in men with culture-confirmed U.S. NmNG urethritis clade infection and points to the strong association of this clade with disease. |
Infection With the US Neisseria meningitidis Urethritis Clade Does Not Lower Future Risk of Urethral Gonorrhea.
Norris Turner A , Carter A , Tzeng YL , Stephens DS , Brown M , Snyder B , Retchless AC , Wang X , Bazan JA . Clin Infect Dis 2021 74 (12) 2159-2165 ![]() ![]() BACKGROUND: Cross-protective immunity between Neisseria meninigitidis (Nm) and Neisseria gonorrhoeae (Ng) may inform gonococcal vaccine development. Meningococcal serogroup B (MenB) outer membrane vesicle (OMV) vaccines confer modest protection against gonorrhea. However, whether urethral Nm infection protects against gonorrhea is unknown. We examined gonorrhea risk among men with US Nm urethritis clade (US_NmUC) infections. METHODS: We conducted a retrospective cohort study of men with urethral US_NmUC (N=128) between January 2015 and April 2018. Using diagnosis date as the baseline visit, we examined Ng status at return visits to compute urethral Ng risk. We compared these data to three referent populations: men with urethral Ng (N=253), urethral chlamydia (Ct) (N=251), and no urethral Ng or Ct (N=255). We conducted sensitivity analyses to assess varied approaches to censoring, missing data, and anatomical site of infection. We also compared sequences of protein antigens in the OMV-based MenB-4C vaccine, US_NmUC, and Ng. RESULTS: Participants were primarily Black (65%) and heterosexual (82%). Over follow-up, 91 men acquired urethral Ng. Men with urethral US_NmUC had similar Ng risk to men with prior urethral Ng (adjusted hazard ratio (AHR): 1∙27, 95% CI: 0∙65-2∙48). Men with urethral US_NmUC had insignificantly increased Ng risk compared to men with urethral Ct (AHR: 1∙51, 95% CI: 0∙79-2∙88), and significantly increased Ng risk compared to men without urethral Ng or Ct (AHR: 3∙55, 95% CI: 1∙27-9∙91). Most of the protein antigens analyzed shared high sequence similarity. CONCLUSIONS: Urethral US_NmUC infection did not protect against gonorrhea despite substantial sequence similarities in shared protein antigens. |
Genomic Surveillance for SARS-CoV-2 Variants Circulating in the United States, December 2020-May 2021.
Paul P , France AM , Aoki Y , Batra D , Biggerstaff M , Dugan V , Galloway S , Hall AJ , Johansson MA , Kondor RJ , Halpin AL , Lee B , Lee JS , Limbago B , MacNeil A , MacCannell D , Paden CR , Queen K , Reese HE , Retchless AC , Slayton RB , Steele M , Tong S , Walters MS , Wentworth DE , Silk BJ . MMWR Morb Mortal Wkly Rep 2021 70 (23) 846-850 ![]() SARS-CoV-2, the virus that causes COVID-19, is constantly mutating, leading to new variants (1). Variants have the potential to affect transmission, disease severity, diagnostics, therapeutics, and natural and vaccine-induced immunity. In November 2020, CDC established national surveillance for SARS-CoV-2 variants using genomic sequencing. As of May 6, 2021, sequences from 177,044 SARS-CoV-2-positive specimens collected during December 20, 2020-May 6, 2021, from 55 U.S. jurisdictions had been generated by or reported to CDC. These included 3,275 sequences for the 2-week period ending January 2, 2021, compared with 25,000 sequences for the 2-week period ending April 24, 2021 (0.1% and 3.1% of reported positive SARS-CoV-2 tests, respectively). Because sequences might be generated by multiple laboratories and sequence availability varies both geographically and over time, CDC developed statistical weighting and variance estimation methods to generate population-based estimates of the proportions of identified variants among SARS-CoV-2 infections circulating nationwide and in each of the 10 U.S. Department of Health and Human Services (HHS) geographic regions.* During the 2-week period ending April 24, 2021, the B.1.1.7 and P.1 variants represented an estimated 66.0% and 5.0% of U.S. SARS-CoV-2 infections, respectively, demonstrating the rise to predominance of the B.1.1.7 variant of concern(†) (VOC) and emergence of the P.1 VOC in the United States. Using SARS-CoV-2 genomic surveillance methods to analyze surveillance data produces timely population-based estimates of the proportions of variants circulating nationally and regionally. Surveillance findings demonstrate the potential for new variants to emerge and become predominant, and the importance of robust genomic surveillance. Along with efforts to characterize the clinical and public health impact of SARS-CoV-2 variants, surveillance can help guide interventions to control the COVID-19 pandemic in the United States. |
Using Neisseria meningitidis genomic diversity to inform outbreak strain identification.
Retchless AC , Chen A , Chang HY , Blain AE , McNamara LA , Mustapha MM , Harrison LH , Wang X . PLoS Pathog 2021 17 (5) e1009586 ![]() ![]() Meningococcal disease is a life-threatening illness caused by the human-restricted bacterium Neisseria meningitidis. Outbreaks in the USA involve at least two cases in an organization or community caused by the same serogroup within three months. Genome comparisons, including phylogenetic analysis and quantification of genome distances can provide confirmatory evidence of pathogen transmission during an outbreak. Interpreting genome distances depends on understanding their distribution both among isolates from outbreaks and among those not from outbreaks. Here, we identify outbreak strains based on phylogenetic relationships among 141 N. meningitidis isolates collected from 28 outbreaks in the USA during 2010-2017 and 1516 non-outbreak isolates collected through contemporaneous meningococcal surveillance. We show that genome distance thresholds based on the maximum SNPs and allele distances among isolates in the phylogenetically defined outbreak strains are sufficient to separate most pairs of non-outbreak isolates into separate strains. Non-outbreak isolate pairs that could not be distinguished from each other based on genetic distances were concentrated in the clonal complexes CC11, CC103, and CC32. Within each of these clonal complexes, phylodynamic analysis identified a group of isolates with extremely low diversity, collected over several years and multiple states. Clusters of isolates with low genetic diversity could indicate increased pathogen transmission, potentially resulting in local outbreaks or nationwide clonal expansions. |
Genetic Diversity of Meningococcal Serogroup B Vaccine Antigens among Carriage Isolates Collected from Students at Three Universities in the United States, 2015-2016.
Marjuki H , Chang HY , Topaz N , Whaley MJ , Vuong J , Chen A , Jenkins LT , Hu F , Schmink S , Retchless AC , Thomas JD , Acosta AM , McNamara LA , Soeters HM , Mbaeyi S , Wang X . mBio 2021 12 (3) ![]() ![]() Carriage evaluations were conducted during 2015 to 2016 at two U.S. universities in conjunction with the response to disease outbreaks caused by Neisseria meningitidis serogroup B and at a university where outbreak and response activities had not occurred. All eligible students at the two universities received the serogroup B meningococcal factor H binding protein vaccine (MenB-FHbp); 5.2% of students (181/3,509) at one university received MenB-4C. A total of 1,514 meningococcal carriage isolates were obtained from 8,905 oropharyngeal swabs from 7,001 unique participants. Whole-genome sequencing data were analyzed to understand MenB-FHbp's impact on carriage and antigen genetic diversity and distribution. Of 1,422 isolates from carriers with known vaccination status (726 [51.0%] from MenB-FHbp-vaccinated, 42 [3.0%] from MenB-4C-vaccinated, and 654 [46.0%] from unvaccinated participants), 1,406 (98.9%) had intact fHbp alleles (716 from MenB-FHbp-vaccinated participants). Of 726 isolates from MenB-FHbp-vaccinated participants, 250 (34.4%) harbored FHbp peptides that may be covered by MenB-FHbp. Genogroup B was detected in 122/1,422 (8.6%) and 112/1,422 (7.9%) isolates from MenB-FHbp-vaccinated and unvaccinated participants, respectively. FHbp subfamily and peptide distributions between MenB-FHbp-vaccinated and unvaccinated participants were not statistically different. Eighteen of 161 MenB-FHbp-vaccinated repeat carriers (11.2%) acquired a new strain containing one or more new vaccine antigen peptides during multiple rounds of sample collection, which was not statistically different (P = 0.3176) from the unvaccinated repeat carriers (1/30; 3.3%). Our findings suggest that lack of MenB vaccine impact on carriage was not due to missing the intact fHbp gene; MenB-FHbp did not affect antigen genetic diversity and distribution during the study period.IMPORTANCE The impact of serogroup B meningococcal (MenB) vaccines on carriage is not completely understood. Using whole-genome sequencing data, we assessed the diversity and distribution of MenB vaccine antigens (particularly FHbp) among 1,514 meningococcal carriage isolates recovered from vaccinated and unvaccinated students at three U.S. universities, two of which underwent MenB-FHbp mass vaccination campaigns following meningococcal disease outbreaks. The majority of carriage isolates recovered from participants harbored intact fHbp genes, about half of which were recovered from MenB-FHbp-vaccinated participants. The distribution of vaccine antigen peptides was similar among carriage isolates recovered from vaccinated and unvaccinated participants, and almost all strains recovered from repeat carriers retained the same vaccine antigen profile, suggesting insignificant vaccine selective pressure on the carriage population in these universities. |
Acquisition of ciprofloxacin resistance among an expanding clade of β-lactamase positive, serogroup Y Neisseria meningitidis in the United States.
Potts CC , Retchless AC , McNamara LA , Marasini D , Reese N , Swint S , Hu F , Sharma S , Blain AE , Lonsway D , Karlsson M , Hariri S , Fox LM , Wang X . Clin Infect Dis 2021 73 (7) 1185-1193 ![]() ![]() BACKGROUND: Penicillin and ciprofloxacin are important for invasive meningococcal disease (IMD) management and prevention. IMD cases caused by penicillin- and ciprofloxacin-resistant Neisseria meningitidis containing a ROB-1 β-lactamase gene (blaROB-1) and a mutated DNA gyrase gene (gyrA), have been recently reported in the USA. METHODS: We examined 2097 meningococcal genomes collected through US population-based surveillance from January 2011-February 2020 to identify IMD cases caused by strains with blaROB-1 or gyrA-mediated resistance. Antimicrobial resistance was confirmed phenotypically. The US isolate genomes were compared to non-US isolate genomes containing blaROB-1. Interspecies transfer of ciprofloxacin resistance was assessed by comparing gyrA among Neisseria species. RESULTS: Eleven penicillin- and ciprofloxacin-resistant isolates were identified after December 2018; all were serogroup Y, sequence type 3587, clonal complex (CC) 23, and contained blaROB-1 and a T91I-containing gyrA allele. An additional 22 penicillin-resistant, blaROB-1-containing US isolates with wild-type gyrA were identified from 2013-2020. All 33 blaROB-1-containing isolates formed a single clade, along with 12 blaROB-1-containing isolates from six other countries. Two-thirds of blaROB-1-containing US isolates were from Hispanic individuals. Twelve additional ciprofloxacin-resistant isolates with gyrA T91 mutations were identified. Ciprofloxacin-resistant isolates belonged to six CCs and contained 10 unique gyrA alleles; seven were similar or identical to alleles from N. lactamica or N. gonorrhoeae. CONCLUSIONS: Recent IMD cases caused by a dual resistant serogroup Y suggest changing antimicrobial resistance patterns in the USA. The emerging dual-resistance is due to acquisition of ciprofloxacin resistance by β-lactamase-containing N. meningitidis. Routine antimicrobial resistance surveillance will effectively monitor resistance changes and spread. |
Web-Based Genome Analysis of Bacterial Meningitis Pathogens for Public Health Applications Using the Bacterial Meningitis Genomic Analysis Platform (BMGAP).
Buono SA , Kelly RJ , Topaz N , Retchless AC , Silva H , Chen A , Ramos E , Doho G , Khan AN , Okomo-Adhiambo MA , Hu F , Marasini D , Wang X . Front Genet 2020 11 601870 ![]() ![]() Effective laboratory-based surveillance and public health response to bacterial meningitis depends on timely characterization of bacterial meningitis pathogens. Traditionally, characterizing bacterial meningitis pathogens such as Neisseria meningitidis (Nm) and Haemophilus influenzae (Hi) required several biochemical and molecular tests. Whole genome sequencing (WGS) has enabled the development of pipelines capable of characterizing the given pathogen with equivalent results to many of the traditional tests. Here, we present the Bacterial Meningitis Genomic Analysis Platform (BMGAP): a secure, web-accessible informatics platform that facilitates automated analysis of WGS data in public health laboratories. BMGAP is a pipeline comprised of several components, including both widely used, open-source third-party software and customized analysis modules for the specific target pathogens. BMGAP performs de novo draft genome assembly and identifies the bacterial species by whole-genome comparisons against a curated reference collection of 17 focal species including Nm, Hi, and other closely related species. Genomes identified as Nm or Hi undergo multi-locus sequence typing (MLST) and capsule characterization. Further typing information is captured from Nm genomes, such as peptides for the vaccine antigens FHbp, NadA, and NhbA. Assembled genomes are retained in the BMGAP database, serving as a repository for genomic comparisons. BMGAP's species identification and capsule characterization modules were validated using PCR and slide agglutination from 446 bacterial invasive isolates (273 Nm from nine different serogroups, 150 Hi from seven different serotypes, and 23 from nine other species) collected from 2017 to 2019 through surveillance programs. Among the validation isolates, BMGAP correctly identified the species for all 440 isolates (100% sensitivity and specificity) and accurately characterized all Nm serogroups (99% sensitivity and 98% specificity) and Hi serotypes (100% sensitivity and specificity). BMGAP provides an automated, multi-species analysis pipeline that can be extended to include additional analysis modules as needed. This provides easy-to-interpret and validated Nm and Hi genome analysis capacity to public health laboratories and collaborators. As the BMGAP database accumulates more genomic data, it grows as a valuable resource for rapid comparative genomic analyses during outbreak investigations. |
Full Molecular Typing of Neisseria meningitidis Directly from Clinical Specimens for Outbreak Investigation.
Itsko M , Retchless AC , Joseph SJ , Turner AN , Bazan JA , Sadji AY , Ouédraogo-Traoré R , Wang X . J Clin Microbiol 2020 58 (12) ![]() ![]() Neisseria meningitidis (Nm) is a leading cause of bacterial meningitis and sepsis worldwide and an occasional cause of meningococcal urethritis. When isolates are unavailable for surveillance or outbreak investigations, molecular characterization of pathogens needs to be performed directly from clinical specimens such as cerebrospinal fluid (CSF), blood, or urine. However, genome sequencing of specimens is challenging because of low bacterial and high human DNA abundances. We developed selective whole genome amplification (SWGA), an isothermal multiple displacement amplification-based method, to efficiently enrich, sequence and de novo assemble Nm DNA from clinical specimens with low bacterial loads. SWGA was validated with 12 CSF specimens from invasive meningococcal disease cases and 12 urine specimens from meningococcal urethritis cases. SWGA increased the mean proportion of Nm reads by 2-3 orders of magnitude enabling identification of at least 90% of the 1605 Nm core genome loci for 50% of the specimens. The validated method was used to investigate two meningitis outbreaks recently reported in Togo and Burkina Faso. Twenty-seven specimens with low bacterial load were processed by SWGA before sequencing and 12 of 27 were successfully assembled to obtain the full molecular typing and vaccine antigen profile of the Nm pathogen, therefore enabling thorough characterization of outbreaks. This method is particularly important for enhancing molecular surveillance in regions with low culture rate. SWGA produces enough reads for phylogenetic and allelic analysis with a low cost. More importantly, the procedure can be extended to enrich other important human bacterial pathogens. |
Beta-lactamase-producing, ciprofloxacin-resistant Neisseria meningitidis isolated from a 5-month-old boy in the United States
Taormina G , Campos J , Sweitzer J , Retchless AC , Lunquest K , McNamara LA , Reese N , Karlsson M , Hanisch B . J Pediatric Infect Dis Soc 2020 10 (3) 379-381 Worldwide, there have been few reports of beta-lactamases causing penicillin resistance in Neisseria meningitidis. The first known case of disease in the United States due to a beta-lactamase-producing, ciprofloxacin-resistant N. meningitidis was recently identified. This has potential implications on standard laboratory testing and empiric management of meningococcal disease. |
Carriage of Neisseria meningitidis in men who have sex with men presenting to public sexual health clinics, New York City.
Ngai S , Weiss D , Bell JA , Majrud D , Zayas G , Crawley A , Kornblum J , Rodriguez-Rivera LD , Quinlan T , Halse TA , Retchless AC , MacNeil J , Pathela P . Sex Transm Dis 2020 47 (8) 541-548 ![]() ![]() BACKGROUND: We conducted a N. meningitidis (Nm) carriage study among men who have sex with men (MSM) to explore possible sexual transmission. METHODS: We paired information on patient characteristics with oropharyngeal, rectal, and urethral Nm culture results to assess associations with Nm carriage among 706 MSM at New York City sexual health clinics. Nm isolates were characterized by whole genome sequencing. RESULTS: Twenty-three percent (163/706) of MSM were Nm carriers. Oropharyngeal carriage was 22.6% (159/703), rectal 0.9% (6/695), and urethral 0.4% (3/696). Oropharyngeal carriage was associated with the following recent (past 30 days) exposures: >3 men kissed (adjusted relative risk (aRR) 1.38; 95% confidence interval [CI] 1.03-1.86), performing oral sex (aRR 1.81; 95% CI 1.04-3.18), and antibiotic use (aRR 0.33; 95% CI 0.19-0.57). Sixteen clonal complexes were identified; 27% belonged to invasive lineages. CONCLUSIONS: Our findings suggest that oral sex and the number of recent kissing partners contribute to Nm carriage in MSM. |
Detection of Ciprofloxacin-Resistant, β-Lactamase-Producing Neisseria meningitidis Serogroup Y Isolates - United States, 2019-2020.
McNamara LA , Potts C , Blain AE , Retchless AC , Reese N , Swint S , Lonsway D , Karlsson M , Lunquest K , Sweitzer JJ , Wang X , Hariri S , Fox LM . MMWR Morb Mortal Wkly Rep 2020 69 (24) 735-739 ![]() ![]() Meningococcal disease is a sudden-onset, life-threatening illness caused by the bacterium Neisseria meningitidis. Prompt empiric antibiotic treatment can reduce morbidity and mortality among patients, and antibiotic prophylaxis can prevent secondary disease in close contacts. Historically, N. meningitidis isolates in the United States have largely been susceptible to the antibiotics recommended for treatment and prophylaxis, including penicillin and ciprofloxacin. This report describes detection of penicillin-resistant and ciprofloxacin-resistant N. meningitidis serogroup Y (NmY) isolates in the United States. NmY isolates containing a blaROB-1 beta-lactamase enzyme gene conferring resistance to penicillins (1) were recovered from 33 cases reported during 2013-2020. Isolates from 11 of these cases, reported during 2019-2020, harbored a ciprofloxacin resistance-associated mutation in a chromosomal gene (gyrA). Cases were reported from 12 geographically disparate states; a majority of cases (22 of 33, 67%) occurred in Hispanic persons. These cases represent a substantial increase in penicillin-resistant and ciprofloxacin-resistant meningococci in the United States since 2013. Ceftriaxone and cefotaxime, the recommended first-line agents for empiric bacterial meningitis treatment, can continue to be used for treatment, but health care providers should ascertain susceptibility of meningococcal isolates to penicillin before switching to penicillin or ampicillin. Ongoing monitoring for antimicrobial resistance among meningococcal isolates and prophylaxis failures will be important to inform treatment and prophylaxis recommendations. |
Oropharyngeal microbiome of a college population following a meningococcal disease outbreak
Retchless AC , Kretz CB , Rodriguez-Rivera LD , Chen A , Soeters HM , Whaley MJ , Wang X . Sci Rep 2020 10 (1) 632 ![]() Asymptomatic oropharyngeal carriage of Neisseria meningitidis peaks in adolescence and young adulthood. Following a meningococcal disease outbreak at a U.S. college, we profiled the oropharyngeal microbiomes of 158 students to identify associations between bacterial community composition and meningococcal carriage or risk factors for carriage, including male gender, smoking, and frequent social mixing. Metagenomic shotgun sequencing identified 268 bacterial taxa at the genus or species level, with Streptococcus, Veillonella, and Rothia species being most abundant. Microbiome composition showed weak associations with meningococcal carriage and risk factors for carriage. N. meningitidis abundance was positively correlated with that of Fusobacterium nucleatum, consistent with hypothesized propionic acid cross-feeding. Additional species had positive abundance correlations with N. meningitidis, including Aggregatibacter aphrophilus, Campylobacter rectus, Catonella morbi, Haemophilus haemolyticus, and Parvimonas micra. N. meningitidis abundance was negatively correlated with unidentified Veillonella species. Several of these species are commonly found in dental plaque, while N. meningitidis is primarily found in the pharynx, suggesting that ecological interactions extend throughout the oral cavity. Although risk factors for meningococcal carriage do not strongly impact most bacterial species in the oropharynx, variation in the upper respiratory tract microbiome may create conditions that are more or less favorable for N. meningitidis carriage. |
A New Sequence Type of Neisseria meningitidis Serogroup C Associated With a 2016 Meningitis Outbreak in Mali.
Sanogo YO , Guindo I , Diarra S , Retchless AC , Abdou M , Coulibaly S , Maiga MF , Coumare M , Diarra B , Chen A , Chang HY , Vuong JT , Acosta AM , Sow S , Novak RT , Wang X . J Infect Dis 2019 220 S190-s197 ![]() ![]() In 2016, Mali reported a bacterial meningitis outbreak consisting of 39 suspected cases between epidemiologic weeks 9 and 17 with 15% case fatality ratio in the health district of Ouelessebougou, 80 kilometers from the capital Bamako. Cerebrospinal fluid specimens from 29 cases were tested by culture and real-time polymerase chain reaction; 22 (76%) were positive for bacterial meningitis pathogens, 16 (73%) of which were Neisseria meningitidis (Nm). Of the Nm-positive specimens, 14 (88%) were N meningitidis serogroup C (NmC), 1 was NmW, and 1 was nongroupable. Eight NmC isolates recovered by culture from the outbreak were characterized using whole genome sequencing. Genomics analysis revealed that all 8 isolates belonged to a new sequence type (ST) 12446 of clonal complex 10217 that formed a distinct clade genetically similar to ST-10217, a NmC strain that recently caused large epidemics of meningitis in Niger and Nigeria. The emergence of a new ST of NmC associated with an outbreak in the African meningitis belt further highlights the need for continued molecular surveillance in the region. |
Toward a Global Genomic Epidemiology of Meningococcal Disease.
Retchless AC , Fox LM , Maiden MCJ , Smith V , Harrison LH , Glennie L , Harrison OB , Wang X . J Infect Dis 2019 220 S266-s273 ![]() ![]() Whole-genome sequencing (WGS) is invaluable for studying the epidemiology of meningococcal disease. Here we provide a perspective on the use of WGS for meningococcal molecular surveillance and outbreak investigation, where it helps to characterize pathogens, predict pathogen traits, identify emerging pathogens, and investigate pathogen transmission during outbreaks. Standardization of WGS workflows has facilitated their implementation by clinical and public health laboratories (PHLs), but further development is required for metagenomic shotgun sequencing and targeted sequencing to be widely available for culture-free characterization of bacterial meningitis pathogens. Internet-accessible servers are being established to support bioinformatics analysis, data management, and data sharing among PHLs. However, establishing WGS capacity requires investments in laboratory infrastructure and technical knowledge, which is particularly challenging in resource-limited regions, including the African meningitis belt. Strategic WGS implementation is necessary to monitor the molecular epidemiology of meningococcal disease in these regions and construct a global view of meningococcal disease epidemiology. |
Genomic characterization of Haemophilus influenzae: a focus on the capsule locus.
Potts CC , Topaz N , Rodriguez-Rivera LD , Hu F , Chang HY , Whaley MJ , Schmink S , Retchless AC , Chen A , Ramos E , Doho GH , Wang X . BMC Genomics 2019 20 (1) 733 ![]() ![]() BACKGROUND: Haemophilus influenzae (Hi) can cause invasive diseases such as meningitis, pneumonia, or sepsis. Typeable Hi includes six serotypes (a through f), each expressing a unique capsular polysaccharide. The capsule, encoded by the genes within the capsule locus, is a major virulence factor of typeable Hi. Non-typeable (NTHi) does not express capsule and is associated with invasive and non-invasive diseases. METHODS: A total of 395 typeable and 293 NTHi isolates were characterized by whole genome sequencing (WGS). Phylogenetic analysis and multilocus sequence typing were used to characterize the overall genetic diversity. Pair-wise comparisons were used to evaluate the capsule loci. A WGS serotyping method was developed to predict the Hi serotype. WGS serotyping results were compared to slide agglutination (SAST) or real-time PCR (rt-PCR) serotyping. RESULTS: Isolates of each Hi serotype clustered into one or two subclades, with each subclade being associated with a distinct sequence type (ST). NTHi isolates were genetically diverse, with seven subclades and 125 STs being detected. Regions I and III of the capsule locus were conserved among the six serotypes (>/=82% nucleotide identity). In contrast, genes in Region II were less conserved, with only six gene pairs from all serotypes showing >/=56% nucleotide identity. The WGS serotyping method was 99.9% concordant with SAST and 100% concordant with rt-PCR in determining the Hi serotype. CONCLUSIONS: Genomic analysis revealed a higher degree of genetic diversity among NTHi compared to typeable Hi. The WGS serotyping method accurately predicted the Hi capsule type and can serve as an alternative method for Hi serotyping. |
Patterns of inter- and intrasubspecific homologous recombination inform eco-evolutionary dynamics of Xylella fastidiosa.
Potnis N , Kandel PP , Merfa MV , Retchless AC , Parker JK , Stenger DC , Almeida RPP , Bergsma-Vlami M , Westenberg M , Cobine PA , De La Fuente L . ISME J 2019 13 (9) 2319-2333 ![]() High rates of homologous recombination (HR) in the bacterial plant pathogen Xylella fastidiosa have been previously detected. This study aimed to determine the extent and explore the ecological significance of HR in the genomes of recombinants experimentally generated by natural transformation and wild-type isolates. Both sets of strains displayed widespread HR and similar average size of recombined fragments consisting of random events (2-10 kb) of inter- and intrasubspecific recombination. A significantly higher proportion and greater lengths (>10 kb, maximum 31.5 kb) of recombined fragments were observed in subsp. morus and in strains isolated in Europe from intercepted coffee plants shipped from the Americas. Such highly recombinant strains pose a serious risk of emergence of novel variants, as genetically distinct and formerly geographically isolated genotypes are brought in close proximity by global trade. Recently recombined regions in wild-type strains included genes involved in regulation and signaling, host colonization, nutrient acquisition, and host evasion, all fundamental traits for X. fastidiosa ecology. Identification of four recombinant loci shared between wild-type and experimentally generated recombinants suggests potential hotspots of recombination in this naturally competent pathogen. These findings provide insights into evolutionary forces possibly affecting the adaptive potential to colonize the host environments of X. fastidiosa. |
Distribution of Neisseria meningitidis serogroup B (NmB) vaccine antigens in meningococcal disease causing isolates in the United States during 2009-2014, prior to NmB vaccine licensure.
Chang HY , Vuong J , Hu F , Liberator P , Chen A , Kretz CB , Blain A , Hao L , Retchless AC , Whaley MJ , Anderson AS , Wang X . J Infect 2019 79 (5) 426-434 ![]() OBJECTIVES: Two Neisseria meningitidis serogroup B (NmB) vaccines are licensed in the United States. To estimate their potential coverage, we examined the vaccine antigen diversity among meningococcal isolates prior to vaccine licensure. METHODS: NmB vaccine antigen genes of invasive isolates collected in the U.S. from 2009-2014 were characterized by Sanger or whole-genome sequencing. RESULTS: During 2009-2014, the predominant antigen types have remained similar to those reported in 2000-2008 for NmB and 2006-2008 for NmC, NmY, with the emergence of a few new types. FHbp of subfamily B or variant 1 (B/v1) remained prevalent among NmB whereas FHbp of subfamily A or variant 2 and 3 (A/v2-3) were more prevalent among non-NmB. FHbp peptide 1 (B24/1.1) remains the most prevalent type in NmB. Full-length NadA peptide was detected in 26% of isolates, primarily in NmB and NmW. The greatest diversity of NhbA peptides was detected among NmB, with p0005 as the most prevalent type. CONCLUSIONS: The prevalence and diversity of the NmB vaccine antigens have remained stable with common antigen types persisting over time. The data collected prior to NmB vaccine licensure provide the baseline to understand the potential impact of NmB vaccines on antigen diversity and strain coverage. |
Heteroresistance to the model antimicrobial peptide polymyxin B in the emerging Neisseria meningitidis linage11.2 urethritis clade: mutations in the pilMNOPQ operon.
Tzeng YL , Berman Z , Toh E , Bazan JA , Turner AN , Retchless AC , Wang X , Nelson DE , Stephens DS . Mol Microbiol 2019 111 (1) 254-268 ![]() Clusters of Neisseria meningitidis (Nm) urethritis among primarily heterosexual males in multiple US cities have been attributed to a unique non-encapsulated meningococcal clade (the US Nm urethritis clade, US_NmUC) within the hypervirulent clonal complex 11. Resistance to antimicrobial peptides (AMPs) is a key feature of urogenital pathogenesis of the closely related species, Neisseria gonorrhoeae. The US_NmUC isolates were found to be highly resistant to the model AMP, polymyxin B (PmB, MICs 64-256 microg ml(-1) ). The isolates also demonstrated stable subpopulations of heteroresistant colonies that showed near total resistant to PmB (MICs 384-1024 microg ml(-1) ) and colistin (MIC 256 microg ml(-1) ) as well as enhanced LL-37 resistance. This is the first observation of heteroresistance in N. meningitidis. Consistent with previous findings, overall PmB resistance in US_NmUC isolates was due to active Mtr efflux and LptA-mediated lipid A modification. However, whole genome sequencing, variant analyses and directed mutagenesis revealed that the heteroresistance phenotypes and very high-level AMP resistance were the result of point mutations and IS1655 element movement in the pilMNOPQ operon, encoding the type IV pilin biogenesis apparatus. Cross-resistance to other classes of antibiotics was also observed in the heteroresistant colonies. High-level resistance to AMPs may contribute to the pathogenesis of US_NmUC. |
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