Last data update: Apr 22, 2024. (Total: 46599 publications since 2009)
Records 1-6 (of 6 Records) |
Query Trace: Reimche JL [original query] |
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Novel strain of multidrug non-susceptible Neisseria gonorrhoeae in the USA
Reimche JL , Pham CD , Joseph SJ , Hutton S , Cartee JC , Ruan Y , Breaux M , Ivanof C , Joshi A , DeMartino M , Kirby JE , Barbee LA , Kersh EN , Roosevelt KA , Hsu KK . Lancet Infect Dis 2024 Unsuccessful treatment of gonorrhoea has not yet occurred in the USA, and cases of gonorrhoea that are non-susceptible to cephalosporins have been rare. In 2019, non-susceptibility to ceftriaxone conferred by the mosaic penA 60.001 allele was found in a Neisseria gonorrhoeae multilocus sequence type (MLST) 1901 isolate from Nevada.1 In this Correspondence, we present two additional US cases of the penA 60.001 allele identified in MLST 8123, an emerging international multidrug non-susceptible N gonorrhoeae lineage. Although these cases responded to ceftriaxone treatment, N gonorrhoeae isolates from the first known patient (case 1) demonstrated in-vitro non-susceptibility to ceftriaxone as well as non-susceptibility or resistance to drugs previously recommended for front-line treatment. | | In August, 2022, N gonorrhoeae grown from urine culture from a patient with urethritis in primary care in Massachusetts displayed non-susceptibility to cephalosporins (the minimum inhibitory concentrations were 1·0 μg/mL for ceftriaxone and >1·0 μg/mL for cefixime by agar dilution; the minimum inhibitory concentration for cefixime was 1·5 μg/mL by gradient strip) and azithromycin and resistance to ciprofloxacin, penicillin, and tetracycline (appendix pp 6–7). Antimicrobial susceptibility testing was done with gradient strips at the state public health laboratory Massachusetts and then confirmed via agar dilution at the US Centers for Disease Control and Prevention (CDC). The patient (case 1) had already been successfully diagnosed on nucleic acid amplification test (NAAT) with gonorrhoea and was given 500 mg ceftriaxone intramuscularly and asked to return to primary care where, 9 days after treatment, he was asymptomatic, had normal results during examination, and tested negative by urine culture and pharyngeal and rectal NAAT recommended by the Massachusetts sexually transmitted diseases programme to document N gonorrhoeae clearance from any site of infection. The patient reported that he had not travelled outside USA in the 60 days before onset of symptoms. He disclosed female sex worker contacts, but insufficient information was provided to trace the contacts. |
Mechanistic basis for decreased antimicrobial susceptibility in a clinical isolate of Neisseria gonorrhoeae possessing a mosaic-like mtr efflux pump locus (preprint)
Rouquette-Loughlin CE , Reimche JL , Balthazar JT , Dhulipala V , Gernert KM , Kersh EN , Pham CD , Pettus K , Abrams AJ , Trees DL , St Cyr S , Shafer WM . bioRxiv 2018 448712 Recent reports suggest that mosaic-like sequences within the mtr (multiple transferable resistance) efflux pump locus of Neisseria gonorrhoeae likely originating from commensal Neisseria sp. by transformation can increase the ability of gonococci to resist structurally diverse antimicrobials. Thus, acquisition of numerous nucleotide changes within the mtrR gene encoding the transcriptional repressor (MtrR) of the mtrCDE efflux pump-encoding operon or overlapping promoter region for both along with those that cause amino acid changes in the MtrD transporter protein were recently reported to decrease gonococcal susceptibility to numerous antimicrobials, including azithromycin (Azi) (Wadsworth et al. 2018. MBio. doi.org/10.1128/mBio.01419-18). We performed detailed genetic and molecular studies to define the mechanistic basis for why such strains can exhibit decreased susceptibility to MtrCDE antimicrobial substrates including Azi. We report that a strong cis-acting transcriptional impact of a single nucleotide change within the -35 hexamer of the mtrCDE promoter as well gain-of-function amino acid changes at the C-terminal region of MtrD can mechanistically account for the decreased antimicrobial susceptibility of gonococci with a mosaic-like mtr locus.IMPORTANCE Historically, after introduction of an antibiotic for treatment of gonorrhea, strains of N. gonorrhoeae emerge that display clinical resistance due to spontaneous mutation or acquisition of resistance genes. Genetic exchange between members of the Neisseria genus occurring by transformation can cause significant changes in gonococci that impact the structure of an antibiotic target or expression of genes involved in resistance. The results presented herein provide a framework for understanding how mosaic-like DNA sequences from commensal Neisseria that recombine within the gonococcal mtr efflux pump locus function to decrease bacterial susceptibility to antimicrobials including antibiotics used in therapy of gonorrhea. |
Genomic analysis of 1710 surveillance-based Neisseria gonorrhoeae isolates from the USA in 2019 identifies predominant strain types and chromosomal antimicrobial-resistance determinants
Reimche JL , Clemons AA , Chivukula VL , Joseph SJ , Schmerer MW , Pham CD , Schlanger K , St Cyr SB , Kersh EN , Gernert KM . Microb Genom 2023 9 (5) This study characterized high-quality whole-genome sequences of a sentinel, surveillance-based collection of 1710 Neisseria gonorrhoeae (GC) isolates from 2019 collected in the USA as part of the Gonococcal Isolate Surveillance Project (GISP). It aims to provide a detailed report of strain diversity, phylogenetic relationships and resistance determinant profiles associated with reduced susceptibilities to antibiotics of concern. The 1710 isolates represented 164 multilocus sequence types and 21 predominant phylogenetic clades. Common genomic determinants defined most strains' phenotypic, reduced susceptibility to current and historic antibiotics (e.g. bla (TEM) plasmid for penicillin, tetM plasmid for tetracycline, gyrA for ciprofloxacin, 23S rRNA and/or mosaic mtr operon for azithromycin, and mosaic penA for cefixime and ceftriaxone). The most predominant phylogenetic clade accounted for 21 % of the isolates, included a majority of the isolates with low-level elevated MICs to azithromycin (2.0 µg ml(-1)), carried a mosaic mtr operon and variants in PorB, and showed expansion with respect to data previously reported from 2018. The second largest clade predominantly carried the GyrA S91F variant, was largely ciprofloxacin resistant (MIC ≥1.0 µg ml(-1)), and showed significant expansion with respect to 2018. Overall, a low proportion of isolates had medium- to high-level elevated MIC to azithromycin ((≥4.0 µg ml(-1)), based on C2611T or A2059G 23S rRNA variants). One isolate carried the penA 60.001 allele resulting in elevated MICs to cefixime and ceftriaxone of 1.0 µg ml(-1). This high-resolution snapshot of genetic profiles of 1710 GC sequences, through a comparison with 2018 data (1479 GC sequences) within the sentinel system, highlights change in proportions and expansion of select GC strains and the associated genetic mechanisms of resistance. The knowledge gained through molecular surveillance may support rapid identification of outbreaks of concern. Continued monitoring may inform public health responses to limit the development and spread of antibiotic-resistant gonorrhoea. |
Exploring and comparing the structure of sexual networks affected by Neisseria gonorrhoeae using sexual partner services investigation and genomic data.
Town K , Learner ER , Chivukula VL , Mauk K , Reimche JL , Schmerer MW , Black J , Pathela P , Bhattacharyya S , Kerani RP , Gieseker KE , Fukuda A , Sankaran M , McNeil CJ , Spicknall IH , Raphael BH , St Cyr SB , Bernstein K , Kersh EN , Kirkcaldy RD , Schlanger K , Gernert KM . Sex Transm Dis 2021 48 S131-S136 BACKGROUND: Sexual networks are difficult to construct due to incomplete sexual partner data. The proximity of people within a network may be inferred from genetically similar infections. We explored genomic data combined with partner services investigation (PSI) data to extend our understanding of sexual networks affected by Neisseria gonorrhoeae (NG). METHODS: We used 2017-2019 PSI and whole-genome sequencing (WGS) data from eight jurisdictions participating in CDC's Strengthening the United States Response to Resistant Gonorrhea (SURRG) project. Clusters were identified from sexual contacts and through genetically similar NG isolates. Sexual mixing patterns were characterized by describing the clusters by the individual's gender and gender of their sex partners. RESULTS: Our study included 4,627 diagnoses of NG infection (81% sequenced), 2,455 people received a PSI, 393 people were negative contacts of cases, and 495 contacts with unknown NG status. We identified 823 distinct clusters using PSI data combined with WGS data. Of cases that were not linked to any other case using PSI data, 37% were linked when using WGS data. Overall, 40% of PSI cases were allocated to a larger cluster when PSI and WGS data were combined compared with PSI data alone. Mixed clusters containing women, men who report sex with women, and men who report sex with men were common when using the WGS data either alone or in combination with the PSI data. CONCLUSIONS: Combining PSI and WGS data improves our understanding of sexual network connectivity. |
Genomic analysis of the predominant strains and antimicrobial resistance determinants within 1479 Neisseria gonorrhoeae isolates from the U.S. Gonococcal Isolate Surveillance Project in 2018.
Reimche JL , Chivukula VL , Schmerer MW , Joseph SJ , Pham CD , Schlanger K , St Cyr SB , Weinstock HS , Raphael BH , Kersh EN , Gernert KM . Sex Transm Dis 2021 48 S78-S87 BACKGROUND: The prevalence of Neisseria gonorrhoeae (GC) isolates with elevated minimum inhibitory concentrations (MICs) to various antibiotics continues to rise in the U.S. and globally. Genomic analysis provides a powerful tool for surveillance of circulating strains, antimicrobial resistance determinants, and understanding of transmission through a population. METHODS: GC isolates collected from the U.S. Gonococcal Isolate Surveillance Project (GISP) in 2018 (n=1479) were sequenced and characterized. Whole genome sequencing was used to identify sequence types, antimicrobial resistance profiles, and phylogenetic relationships across demographic and geographic populations. RESULTS: Genetic characterization identified that (1) 80% of the GC isolates were represented in 33 multilocus sequence types, (2) isolates clustered in 23 major phylogenetic clusters with select phenotypic and demographic prevalence, and (3) common antimicrobial resistance determinants associated with low-level or high-level decreased susceptibility or resistance to relevant antibiotics. CONCLUSIONS: Characterization of this 2018 GISP genomic dataset, which is the largest U.S. whole genome sequence data set to date, sets the basis for future prospective studies, and establishes a genomic baseline of GC populations for local and national monitoring. |
Mechanistic Basis for Decreased Antimicrobial Susceptibility in a Clinical Isolate of Neisseria gonorrhoeae Possessing a Mosaic-Like mtr Efflux Pump Locus.
Rouquette-Loughlin CE , Reimche JL , Balthazar JT , Dhulipala V , Gernert KM , Kersh EN , Pham CD , Pettus K , Abrams AJ , Trees DL , St Cyr S , Shafer WM . mBio 2018 9 (6) Recent reports suggest that mosaic-like sequences within the mtr (multiple transferable resistance) efflux pump locus of Neisseria gonorrhoeae, likely originating from commensal Neisseria sp. by transformation, can increase the ability of gonococci to resist structurally diverse antimicrobials. Thus, acquisition of numerous nucleotide changes within the mtrR gene encoding the transcriptional repressor (MtrR) of the mtrCDE efflux pump-encoding operon or overlapping promoter region for both along with those that cause amino acid changes in the MtrD transporter protein were recently reported to decrease gonococcal susceptibility to numerous antimicrobials, including azithromycin (Azi) (C. B. Wadsworth, B. J. Arnold, M. R. A. Satar, and Y. H. Grad, mBio 9:e01419-18, 2018, https://doi.org/10.1128/mBio.01419-18). We performed detailed genetic and molecular studies to define the mechanistic basis for why such strains can exhibit decreased susceptibility to MtrCDE antimicrobial substrates, including Azi. We report that a strong cis-acting transcriptional impact of a single nucleotide change within the -35 hexamer of the mtrCDE promoter as well gain-of-function amino acid changes at the C-terminal region of MtrD can mechanistically account for the decreased antimicrobial susceptibility of gonococci with a mosaic-like mtr locus.IMPORTANCE Historically, after introduction of an antibiotic for treatment of gonorrhea, strains of N. gonorrhoeae emerge that display clinical resistance due to spontaneous mutation or acquisition of resistance genes. Genetic exchange between members of the Neisseria genus occurring by transformation can cause significant changes in gonococci that impact the structure of an antibiotic target or expression of genes involved in resistance. The results presented here provide a framework for understanding how mosaic-like DNA sequences from commensal Neisseria that recombine within the gonococcal mtr efflux pump locus function to decrease bacterial susceptibility to antimicrobials, including antibiotics used in therapy of gonorrhea. |
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