Last data update: Apr 22, 2024. (Total: 46599 publications since 2009)
Records 1-30 (of 82 Records) |
Query Trace: Batra D [original query] |
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Correction for Weigand et al., Complete Genome Sequences of Two Bordetella hinzii Strains Isolated from Humans.
Weigand MR , Changayil S , Kulasekarapandian Y , Batra D , Loparev V , Juieng P , Rowe L , Sheth M , Davis JK , Tondella ML . Genome Announc 2016 4 (1) Volume 3, no. 4, e00965-15, 2015. Page 1: The byline and affiliation line should read as given above. |
Proteomic and genetic analyses of influenza A viruses identify pan-viral host targets
Haas KM , McGregor MJ , Bouhaddou M , Polacco BJ , Kim EY , Nguyen TT , Newton BW , Urbanowski M , Kim H , Williams MAP , Rezelj VV , Hardy A , Fossati A , Stevenson EJ , Sukerman E , Kim T , Penugonda S , Moreno E , Braberg H , Zhou Y , Metreveli G , Harjai B , Tummino TA , Melnyk JE , Soucheray M , Batra J , Pache L , Martin-Sancho L , Carlson-Stevermer J , Jureka AS , Basler CF , Shokat KM , Shoichet BK , Shriver LP , Johnson JR , Shaw ML , Chanda SK , Roden DM , Carter TC , Kottyan LC , Chisholm RL , Pacheco JA , Smith ME , Schrodi SJ , Albrecht RA , Vignuzzi M , Zuliani-Alvarez L , Swaney DL , Eckhardt M , Wolinsky SM , White KM , Hultquist JF , Kaake RM , García-Sastre A , Krogan NJ . Nat Commun 2023 14 (1) 6030 Influenza A Virus (IAV) is a recurring respiratory virus with limited availability of antiviral therapies. Understanding host proteins essential for IAV infection can identify targets for alternative host-directed therapies (HDTs). Using affinity purification-mass spectrometry and global phosphoproteomic and protein abundance analyses using three IAV strains (pH1N1, H3N2, H5N1) in three human cell types (A549, NHBE, THP-1), we map 332 IAV-human protein-protein interactions and identify 13 IAV-modulated kinases. Whole exome sequencing of patients who experienced severe influenza reveals several genes, including scaffold protein AHNAK, with predicted loss-of-function variants that are also identified in our proteomic analyses. Of our identified host factors, 54 significantly alter IAV infection upon siRNA knockdown, and two factors, AHNAK and coatomer subunit COPB1, are also essential for productive infection by SARS-CoV-2. Finally, 16 compounds targeting our identified host factors suppress IAV replication, with two targeting CDK2 and FLT3 showing pan-antiviral activity across influenza and coronavirus families. This study provides a comprehensive network model of IAV infection in human cells, identifying functional host targets for pan-viral HDT. |
Corrigendum: Characterization of a novel transitional group Rickettsia species (Rickettsia tillamookensis sp. nov.) from the western black-legged tick, Ixodes pacificus
Gauthier DT , Karpathy SE , Grizzard SL , Batra D , Rowe LA , Paddock CD . Int J Syst Evol Microbiol 2023 73 (8) In the published version of this article there was an error with the sequence data. Please see the corrected text below: | | | In the abstract | | Upon reanalysis with corrected 16S rRNA sequence, the closest full-length match to non-genome strains in Genbank at the time of this corrigendum was to ‘Candidatus Rickettsia senegalensis’ strain R184 (Genbank accession number OM311169) at 99.7 % identity. | | | In table 1 | | The 16S rRNA column analysis was performed with the chimeric 16S rRNA sequence and is thus in error. The top non-genome strain match and identity is as described for changes to the Abstract. The best match to a complete genome was to R. felis URRWXCal2 (Genbank CP000053) at 99.8 % identity. | | | In phylogeny | | 16S rRNA comparisons are in error and are corrected as for Abstract and Table 1. | | In summary, we have, through antibiotic clearance of Mycoplasma contamination of R. tillamookensis Tillamook 23T, ascertained that corrections need to be made to the published genome record for 16S and 23S rRNA sequences. Genbank records have been updated accordingly. These changes do not affect the status of R. tillamookensis as a distinct species or its phylogenetic placement among the transitional group of Rickettsia. | | The authors have provided a detailed explanation of this correction in the Supplementary File 1. | | The authors apologise for any inconvenience caused. | |
Prevalent, protective, and convergent IgG recognition of SARS-CoV-2 non-RBD spike epitopes in COVID-19 convalescent plasma (preprint)
Voss WN , Hou YJ , Johnson NV , Kim JE , Delidakis G , Horton AP , Bartzoka F , Paresi CJ , Tanno Y , Abbasi SA , Pickens W , George K , Boutz DR , Towers DM , McDaniel JR , Billick D , Goike J , Rowe L , Batra D , Pohl J , Lee J , Gangappa S , Sambhara S , Gadush M , Wang N , Person MD , Iverson BL , Gollihar JD , Dye J , Herbert A , Baric RS , McLellan JS , Georgiou G , Lavinder JJ , Ippolito GC . bioRxiv 2020 Although humoral immunity is essential for control of SARS-CoV-2, the molecular composition, binding epitopes and effector functions of the immunoglobulin G (IgG) antibodies that circulate in blood plasma following infection are unknown. Proteomic deconvolution of the circulating IgG repertoire (Ig-Seq (1) ) to the spike ectodomain (S-ECD (2) ) in four convalescent study subjects revealed that the plasma response is oligoclonal and directed predominantly (>80%) to S-ECD epitopes that lie outside the receptor binding domain (RBD). When comparing antibodies directed to either the RBD, the N-terminal domain (NTD) or the S2 subunit (S2) in one subject, just four IgG lineages (1 anti-S2, 2 anti-NTD and 1 anti-RBD) accounted for 93.5% of the repertoire. Although the anti-RBD and one of the anti-NTD antibodies were equally potently neutralizing in vitro , we nonetheless found that the anti-NTD antibody was sufficient for protection to lethal viral challenge, either alone or in combination as a cocktail where it dominated the effect of the other plasma antibodies. We identified in vivo protective plasma anti-NTD antibodies in 3/4 subjects analyzed and discovered a shared class of antibodies targeting the NTD that utilize unmutated or near-germline IGHV1-24, the most electronegative IGHV gene in the human genome. Structural analysis revealed that binding to NTD is dominated by interactions with the heavy chain, accounting for 89% of the entire interfacial area, with germline residues uniquely encoded by IGHV1-24 contributing 20% (149 Å (2) ). Together with recent reports of germline IGHV1-24 antibodies isolated by B-cell cloning (3,4) our data reveal a class of shared IgG antibodies that are readily observed in convalescent plasma and underscore the role of NTD-directed antibodies in protection against SARS-CoV-2 infection. |
Chromosomal rearrangements and loss of subtelomeric adhesins linked to clade-specific phenotypes in Candida auris (preprint)
Muñoz JF , Welsh RM , Shea T , Batra D , Gade L , Litvintseva AP , Cuomo CA . bioRxiv 2019 754143 Candida auris is an emerging fungal pathogen of rising concern due to its increasing incidence, its ability to cause healthcare-associated outbreaks and antifungal resistance. Genomic analysis revealed that early cases of C. auris that were detected contemporaneously were geographically stratified into four major clades. Clade II, also termed East Asian clade, consists of the initial isolates described from cases of ear infection, is less frequently resistant to antifungal drugs and to date, the isolates from this group have not been associated with outbreaks. Here, we generate nearly complete genomes (“telomere-to-telomere”) of an isolate of this clade and of the more widespread Clade IV. By comparing these to genome assemblies of the other two clades, we find that the Clade II genome appears highly rearranged, with 2 inversions and 9 translocations resulting in a substantially different karyotype. In addition, large subtelomeric regions have been lost from 10 of 14 chromosome ends in the Clade II genomes. We find that shorter telomeres and genome instability might be a consequence of a naturally occurring loss-of-function mutation in DCC1 exclusively found in Clade II isolates, resulting in a hypermutator phenotype. We also determine that deleted subtelomeric regions might be linked to clade-specific adaptation as these regions are enriched in Hyr/Iff-like cell surface proteins, novel candidate cell surface proteins, and an ALS-like adhesin. The presence of these cell surface proteins in the clades responsible for global outbreaks causing invasive infections suggests an explanation for the different phenotypes observed between clades.IMPORTANCE Candida auris was unknown prior to 2009 and since then it has quickly spread around the world, causing outbreaks in healthcare facilities and representing a high fraction of candidemia cases in some regions. The emergence of C. auris is a major concern, since it is often multidrug-resistant, easily spread between patients, and causes invasive infections. While isolates from three global clades cause invasive infections, isolates from Clade II primarily cause ear infections and have not been implicated in outbreaks, though cases of Clade II infections have been reported on different continents. Here, we describe genetic differences between Clade II and Clades I, III and IV, including a loss-of-function mutation in a gene associated with telomere length maintenance and genome stability, and the loss of cell wall proteins involved in adhesion and biofilm formation, that may suggest an explanation for the lower virulence and potential for transmission of Clade II isolates. |
Multiple lineages of Monkeypox virus detected in the United States, 2021-2022 (preprint)
Gigante CM , Korber B , Seabolt MH , Wilkins K , Davidson W , Rao AK , Zhao H , Hughes CM , Minhaj F , Waltenburg MA , Theiler J , Smole S , Gallagher GR , Blythe D , Myers R , Schulte J , Stringer J , Lee P , Mendoza RM , Griffin-Thomas LA , Crain J , Murray J , Atkinson A , Gonzalez AH , Nash J , Batra D , Damon I , McQuiston J , Hutson CL , McCollum AM , Li Y . bioRxiv 2022 11 (6619) 560-565 Monkeypox is a viral zoonotic disease endemic in Central and West Africa. In May 2022, dozens of non-endemic countries reported hundreds of monkeypox cases, most with no epidemiological link to Africa. We identified two lineages of Monkeypox virus (MPXV) among nine 2021 and 2022 U.S. monkeypox cases. A 2021 case was highly similar to the 2022 MPXV outbreak variant, suggesting a common ancestor. Analysis of mutations among these two lineages revealed an extreme preference for GA-to-AA mutations indicative of APOBEC3 cytosine deaminase activity that was shared among West African MPXV since 2017 but absent from Congo Basin lineages. Poxviruses are not thought to be subject to APOBEC3 editing; however, these findings suggest APOBEC3 activity has been recurrent and dominant in recent West African MPXV evolution. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Genomic deletions and rearrangements in monkeypox virus from the 2022 outbreak, USA (preprint)
Gigante CM , Plumb M , Ruprecht A , Zhao H , Wicker V , Wilkins K , Matheny A , Khan T , Davidson W , Sheth M , Burgin A , Burroughs M , Padilla J , Lee JS , Batra D , Hetrick EE , Howard DT , Garfin J , Tate L , Hubsmith SJ , Mendoza RM , Stanek D , Gillani S , Lee M , Mangla A , Blythe D , SierraPatev S , Carpenter-Azevedo K , Huard RC , Gallagher G , Hall J , Ash S , Kovar L , Seabolt MH , Weigand MR , Damon I , Satheshkumar PS , McCollum AM , Hutson CL , Wang X , Li Y . bioRxiv 2022 17 Genomic surveillance of monkeypox virus (MPXV) during the 2022 outbreak has been mainly focused on single nucleotide polymorphism (SNP) changes. DNA viruses, including MPXV, have a lower SNP mutation rate than RNA viruses due to higher fidelity replication machinery. We identified a large genomic rearrangement in a MPXV sequence from a 2022 case in the state of Minnesota (MN), USA, from an abnormal, uneven MPXV read mapping coverage profile in whole-genome sequencing (WGS) data. We further screened WGS data of 206 U.S. MPXV samples and found seven (3.4 percent) sequenced genomes contained similar abnormal read coverage profiles that suggested putative large deletions or genomic rearrangements. Here, we present three MPXV genomes containing deletions ranging from 2.3 to 15 kb and four genomes containing more complex rearrangements. Five genomic changes were each only seen in one sample, but two sequences from linked cases shared an identical 2.3 kb deletion in the 3' terminal region. All samples were positive using VAC1 and Clade II (formerly West African)-specific MPXV diagnostic tests; however, large deletions and genomic rearrangements like the ones reported here have the potential to result in viruses in which the target of a PCR diagnostic test is deleted. The emergence of genomic rearrangements during the outbreak may have public health implications and highlight the importance of continued genomic surveillance. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Identification of a Novel SARS-CoV-2 Delta-Omicron Recombinant Virus in the United States (preprint)
Lacek KA , Rambo-Martin BL , Batra D , Zheng XY , Sakaguchi H , Peacock T , Keller M , Wilson MM , Sheth M , Davis ML , Borroughs M , Gerhart J , Hassell N , Shepard SS , Cook PW , Lee J , Wentworth DE , Barnes JR , Kondor R , Paden CR . bioRxiv 2022 21 Recombination between SARS-CoV-2 virus variants can result in different viral properties (e.g., infectiousness or pathogenicity). In this report, we describe viruses with recombinant genomes containing signature mutations from Delta and Omicron variants. These genomes are the first evidence for a Delta-Omicron hybrid Spike protein in the United States. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Differential neutralization and inhibition of SARS-CoV-2 variants by antibodies elicited by COVID-19 mRNA vaccines (preprint)
Wang L , Kainulainen MH , Jiang N , Di H , Bonenfant G , Mills L , Currier M , Shrivastava-Ranjan P , Calderon BM , Sheth M , Hossain J , Lin X , Lester S , Pusch E , Jones J , Cui D , Chatterjee P , Jenks HM , Morantz E , Larson G , Hatta M , Harcourt J , Tamin A , Li Y , Tao Y , Zhao K , Burroughs A , Wong T , Tong S , Barnes JR , Tenforde MW , Self WH , Shapiro NI , Exline MC , Files DC , Gibbs KW , Hager DN , Patel M , Laufer Halpin AS , Lee JS , Xie X , Shi PY , Davis CT , Spiropoulou CF , Thornburg NJ , Oberste MS , Dugan V , Wentworth DE , Zhou B , Batra D , Beck A , Caravas J , Cintron-Moret R , Cook PW , Gerhart J , Gulvik C , Hassell N , Howard D , Knipe K , Kondor RJ , Kovacs N , Lacek K , Mann BR , McMullan LK , Moser K , Paden CR , Martin BR , Schmerer M , Shepard S , Stanton R , Stark T , Sula E , Tymeckia K , Unoarumhi Y . bioRxiv 2021 30 The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in the emergence of many new variant lineages that have exacerbated the COVID-19 pandemic. Some of those variants were designated as variants of concern/interest (VOC/VOI) by national or international authorities based on many factors including their potential impact on vaccines. To ascertain and rank the risk of VOCs and VOIs, we analyzed their ability to escape from vaccine-induced antibodies. The variants showed differential reductions in neutralization and replication titers by post-vaccination sera. Although the Omicron variant showed the most escape from neutralization, sera collected after a third dose of vaccine (booster sera) retained moderate neutralizing activity against that variant. Therefore, vaccination remains the most effective strategy to combat the COVID-19 pandemic. |
Genomic surveillance for SARS-CoV-2 variants: Circulation of Omicron lineages - United States, January 2022-May 2023
Ma KC , Shirk P , Lambrou AS , Hassell N , Zheng XY , Payne AB , Ali AR , Batra D , Caravas J , Chau R , Cook PW , Howard D , Kovacs NA , Lacek KA , Lee JS , MacCannell DR , Malapati L , Mathew S , Mittal N , Nagilla RR , Parikh R , Paul P , Rambo-Martin BL , Shepard SS , Sheth M , Wentworth DE , Winn A , Hall AJ , Silk BJ , Thornburg N , Kondor R , Scobie HM , Paden CR . MMWR Morb Mortal Wkly Rep 2023 72 (24) 651-656 CDC has used national genomic surveillance since December 2020 to monitor SARS-CoV-2 variants that have emerged throughout the COVID-19 pandemic, including the Omicron variant. This report summarizes U.S. trends in variant proportions from national genomic surveillance during January 2022-May 2023. During this period, the Omicron variant remained predominant, with various descendant lineages reaching national predominance (>50% prevalence). During the first half of 2022, BA.1.1 reached predominance by the week ending January 8, 2022, followed by BA.2 (March 26), BA.2.12.1 (May 14), and BA.5 (July 2); the predominance of each variant coincided with surges in COVID-19 cases. The latter half of 2022 was characterized by the circulation of sublineages of BA.2, BA.4, and BA.5 (e.g., BQ.1 and BQ.1.1), some of which independently acquired similar spike protein substitutions associated with immune evasion. By the end of January 2023, XBB.1.5 became predominant. As of May 13, 2023, the most common circulating lineages were XBB.1.5 (61.5%), XBB.1.9.1 (10.0%), and XBB.1.16 (9.4%); XBB.1.16 and XBB.1.16.1 (2.4%), containing the K478R substitution, and XBB.2.3 (3.2%), containing the P521S substitution, had the fastest doubling times at that point. Analytic methods for estimating variant proportions have been updated as the availability of sequencing specimens has declined. The continued evolution of Omicron lineages highlights the importance of genomic surveillance to monitor emerging variants and help guide vaccine development and use of therapeutics. |
Erratum: Vol. 71, No. 6.
Lambrou AS , Shirk P , Steele MK , Paul P , Paden CR , Cadwell B , Reese HE , Aoki Y , Hassell N , Caravas J , Kovacs NA , Gerhart JG , Ng HJ , Zheng XY , Beck A , Chau R , Cintron R , Cook PW , Gulvik CA , Howard D , Jang Y , Knipe K , Lacek KA , Moser KA , Paskey AC , Rambo-Martin BL , Nagilla RR , Rethchless AC , Schmerer MW , Seby S , Shephard SS , Stanton RA , Stark TJ , Uehara A , Unoarumhi Y , Bentz ML , Burhgin A , Burroughs M , Davis ML , Keller MW , Keong LM , Le SS , Lee JS , Madden Jr JC , Nobles S , Owouor DC , Padilla J , Sheth M , Wilson MM , Talarico S , Chen JC , Oberste MS , Batra D , McMullan LK , Halpin AL , Galloway SE , MacCannell DR , Kondor R , Barnes J , MacNeil A , Silk BJ , Dugan VG , Scobie HM , Wentworth DE . MMWR Morb Mortal Wkly Rep 2022 71 (14) 528 The report “Genomic Surveillance for SARS-CoV-2 Variants: Predominance of the Delta (B.1.617.2) and Omicron (B.1.1.529) Variants — United States, June 2021–January 2022” contained several errors. |
Travel history among persons infected with SARS-CoV-2 variants of concern in the United States, December 2020-February 2021.
Dunajcik A , Haire K , Thomas JD , Moriarty LF , Springer Y , Villanueva JM , MacNeil A , Silk B , Nemhauser JB , Byrkit R , Taylor M , Queen K , Tong S , Lee J , Batra D , Paden C , Henderson T , Kunkes A , Ojo M , Firestone M , Martin Webb L , Freeland M , Brown CM , Williams T , Allen K , Kauerauf J , Wilson E , Jain S , McDonald E , Silver E , Stous S , Wadford D , Radcliffe R , Marriott C , Owes JP , Bart SM , Sosa LE , Oakeson K , Wodniak N , Shaffner J , Brown Q , Westergaard R , Salinas A , Hallyburton S , Ogale Y , Offutt-Powell T , Bonner K , Tubach S , Van Houten C , Hughes V , Reeb V , Galeazzi C , Khuntia S , McGee S , Hicks JT , Dinesh Patel D , Krueger A , Hughes S , Jeanty F , Wang JC , Lee EH , Assanah-Deane T , Tompkins M , Dougherty K , Naqvi O , Donahue M , Frederick J , Abdalhamid B , Powers AM , Anderson M . PLOS Glob Public Health 2023 3 (3) e0001252 The first three SARS-CoV-2 phylogenetic lineages classified as variants of concern (VOCs) in the United States (U.S.) from December 15, 2020 to February 28, 2021, Alpha (B.1.1.7), Beta (B.1.351), and Gamma (P.1) lineages, were initially detected internationally. This investigation examined available travel history of coronavirus disease 2019 (COVID-19) cases reported in the U.S. in whom laboratory testing showed one of these initial VOCs. Travel history, demographics, and health outcomes for a convenience sample of persons infected with a SARS-CoV-2 VOC from December 15, 2020 through February 28, 2021 were provided by 35 state and city health departments, and proportion reporting travel was calculated. Of 1,761 confirmed VOC cases analyzed, 1,368 had available data on travel history. Of those with data on travel history, 1,168 (85%) reported no travel preceding laboratory confirmation of SARS-CoV-2 and only 105 (8%) reported international travel during the 30 days preceding a positive SARS-CoV-2 test or symptom onset. International travel was reported by 92/1,304 (7%) of persons infected with the Alpha variant, 7/55 (22%) with Beta, and 5/9 (56%) with Gamma. Of the first three SARS-CoV-2 lineages designated as VOCs in the U.S., international travel was common only among the few Gamma cases. Most persons infected with Alpha and Beta variant reported no travel history, therefore, community transmission of these VOCs was likely common in the U.S. by March 2021. These findings underscore the importance of global surveillance using whole genome sequencing to detect and inform mitigation strategies for emerging SARS-CoV-2 VOCs. |
Genome Sequences of Hemolytic and Nonhemolytic Listeria innocua Strains from Human, Food, and Environmental Sources.
McIntosh T , Kucerova Z , Katz LS , Lilley CM , Rowe LA , Unoarumhi Y , Batra D , Burnett E , Smikle M , Lee C . Microbiol Resour Announc 2022 11 (12) e0072322 This report describes genome sequences for nine Listeria innocua strains that varied in hemolytic phenotypes on sheep blood agar. All strains were sequenced using Pacific Biosciences (PacBio) single-molecule real-time (SMRT) chemistry; overall, the average read length of these sequences was 2,869,880 bp, with an average GC content of 37%. |
The first complete genome of the simian malaria parasite Plasmodium brasilianum.
Bajic M , Ravishankar S , Sheth M , Rowe LA , Pacheco MA , Patel DS , Batra D , Loparev V , Olsen C , Escalante AA , Vannberg F , Udhayakumar V , Barnwell JW , Talundzic E . Sci Rep 2022 12 (1) 19802 Naturally occurring human infections by zoonotic Plasmodium species have been documented for P. knowlesi, P. cynomolgi, P. simium, P. simiovale, P. inui, P. inui-like, P. coatneyi, and P. brasilianum. Accurate detection of each species is complicated by their morphological similarities with other Plasmodium species. PCR-based assays offer a solution but require prior knowledge of adequate genomic targets that can distinguish the species. While whole genomes have been published for P. knowlesi, P. cynomolgi, P. simium, and P. inui, no complete genome for P. brasilianum has been available. Previously, we reported a draft genome for P. brasilianum, and here we report the completed genome for P. brasilianum. The genome is 31.4 Mb in size and comprises 14 chromosomes, the mitochondrial genome, the apicoplast genome, and 29 unplaced contigs. The chromosomes consist of 98.4% nucleotide sites that are identical to the P. malariae genome, the closest evolutionarily related species hypothesized to be the same species as P. brasilianum, with 41,125 non-synonymous SNPs (0.0722% of genome) identified between the two genomes. Furthermore, P. brasilianum had 4864 (82.1%) genes that share 80% or higher sequence similarity with 4970 (75.5%) P. malariae genes. This was demonstrated by the nearly identical genomic organization and multiple sequence alignments for the merozoite surface proteins msp3 and msp7. We observed a distinction in the repeat lengths of the circumsporozoite protein (CSP) gene sequences between P. brasilianum and P. malariae. Our results demonstrate a 97.3% pairwise identity between the P. brasilianum and the P. malariae genomes. These findings highlight the phylogenetic proximity of these two species, suggesting that P. malariae and P. brasilianum are strains of the same species, but this could not be fully evaluated with only a single genomic sequence for each species. |
Genomics and metagenomics of Madurella mycetomatis, a causative agent of black grain mycetoma in Sudan
Litvintseva AP , Bakhiet S , Gade L , Wagner DD , Bagal UR , Batra D , Norris E , Rishishwar L , Beer KD , Siddig EE , Mhmoud NA , Chow NA , Fahal A . PLoS Negl Trop Dis 2022 16 (11) e0010787 Madurella mycetomatis is one of the main causative agents of mycetoma, a debilitating neglected tropical disease. Improved understanding of the genomic diversity of the fungal and bacterial causes of mycetoma is essential to advances in diagnosis and treatment. Here, we describe a high-quality genome assembly of M. mycetomatis and results of the whole genome sequence analysis of 26 isolates from Sudan. We demonstrate evidence of at least seven genetically diverse lineages and extreme clonality among isolates within these lineages. We also performed shotgun metagenomic analysis of DNA extracted from mycetoma grains and showed that M. mycetomatis reads were detected in all sequenced samples with the average of 11,317 reads (s.d. +/- 21,269) per sample. In addition, 10 (12%) of the 81 tested grain samples contained bacterial reads including Streptococcus sp., Staphylococcus sp. and others. |
Multiple lineages of monkeypox virus detected in the United States, 2021-2022.
Gigante CM , Korber B , Seabolt MH , Wilkins K , Davidson W , Rao AK , Zhao H , Smith TG , Hughes CM , Minhaj F , Waltenburg MA , Theiler J , Smole S , Gallagher GR , Blythe D , Myers R , Schulte J , Stringer J , Lee P , Mendoza RM , Griffin-Thomas LA , Crain J , Murray J , Atkinson A , Gonzalez AH , Nash J , Batra D , Damon I , McQuiston J , Hutson CL , McCollum AM , Li Y . Science 2022 378 (6619) eadd4153 Monkeypox is a viral zoonotic disease endemic in Central and West Africa. In May 2022, dozens of non-endemic countries reported hundreds of monkeypox cases, most with no epidemiological link to Africa. We identified two lineages of monkeypox virus (MPXV) among two 2021 and seven 2022 U.S. monkeypox cases: the major 2022 outbreak variant, B.1, and a minor contemporaneously sampled variant called A.2. Analyses of mutations among these two variants revealed an extreme preference for GA-to-AA mutations indicative of human APOBEC3 cytosine deaminase activity among Clade IIb MPXV (previously West African, Nigeria) sampled since 2017. Such mutations were not enriched within other MPXV clades. These findings suggest that APOBEC3 editing may be a recurrent and a dominant driver of MPXV evolution within the current outbreak. |
SARS-CoV-2 Delta-Omicron Recombinant Viruses, United States.
Lacek KA , Rambo-Martin BL , Batra D , Zheng XY , Hassell N , Sakaguchi H , Peacock T , Groves N , Keller M , Wilson MM , Sheth M , Davis ML , Borroughs M , Gerhart J , Shepard SS , Cook PW , Lee J , Wentworth DE , Barnes JR , Kondor R , Paden CR . Emerg Infect Dis 2022 28 (7) 1442-1445 To detect new and changing SARS-CoV-2 variants, we investigated candidate Delta-Omicron recombinant genomes from Centers for Disease Control and Prevention national genomic surveillance. Laboratory and bioinformatic investigations identified and validated 9 genetically related SARS-CoV-2 viruses with a hybrid Delta-Omicron spike protein. |
Sentinel Surveillance Reveals Emerging Daptomycin-Resistant ST736 Enterococcus faecium and Multiple Mechanisms of Linezolid Resistance in Enterococci in the United States.
Gargis AS , Spicer LM , Kent AG , Zhu W , Campbell D , McAllister G , Ewing TO , Albrecht V , Stevens VA , Sheth M , Padilla J , Batra D , Johnson JK , Halpin AL , Rasheed JK , Elkins CA , Karlsson M , Lutgring JD . Front Microbiol 2021 12 807398 Enterococcus faecalis and faecium with resistance to daptomycin and/or linezolid are emerging globally. We present the genomic characterization of daptomycin- and linezolid-resistant E. faecalis and E. faecium surveillance isolates from the United States, 2013-2016. Daptomycin resistance was low among E. faecalis (2/364, 0.5%) and E. faecium (17/344, 5%). The majority (71%, 12/17) of daptomycin-resistant E. faecium isolates belonged to the emerging ST736 clone and contained mutations in liaFSR and cls previously associated with resistance. However, 1/2 E. faecalis and 3/17 E. faecium did not contain these mutations previously associated with daptomycin resistance. Linezolid resistance was rare among E. faecalis (1/364, 0.3%) and E. faecium (2/344, 0.6%). These two E. faecium isolates, one of which was also resistant to daptomycin and vancomycin, contained the 23S rRNA nucleotide mutation (G2576T) associated with linezolid resistance. Long-read sequencing revealed the linezolid-resistant E. faecalis isolate contained chromosomal- and plasmid-encoded copies of optrA. The chromosomal optrA was located on the recently described Tn6674 multiresistance transposon. The second copy of optrA was encoded on an ∼65 kb mosaic plasmid, with component regions sharing high sequence identity to optrA-encoding multiresistance plasmids of animal origin. The optrA-encoding plasmid contained open reading frames predicted to encode proteins associated with a pheromone-responsive plasmid transfer system, and filter mating experiments confirmed the plasmid was conjugative. Continued surveillance of enterococci is necessary to assess the prevalence and trends of daptomycin and linezolid resistance in the United States, characterize resistance mechanisms and how they transfer, and monitor for emerging sequence types associated with resistance. |
Genomic Surveillance for SARS-CoV-2 Variants: Predominance of the Delta (B.1.617.2) and Omicron (B.1.1.529) Variants - United States, June 2021-January 2022.
Lambrou AS , Shirk P , Steele MK , Paul P , Paden CR , Cadwell B , Reese HE , Aoki Y , Hassell N , Caravas J , Kovacs NA , Gerhart JG , Ng HJ , Zheng XY , Beck A , Chau R , Cintron R , Cook PW , Gulvik CA , Howard D , Jang Y , Knipe K , Lacek KA , Moser KA , Paskey AC , Rambo-Martin BL , Nagilla RR , Rethchless AC , Schmerer MW , Seby S , Shephard SS , Stanton RA , Stark TJ , Uehara A , Unoarumhi Y , Bentz ML , Burhgin A , Burroughs M , Davis ML , Keller MW , Keong LM , Le SS , Lee JS , Madden Jr JC , Nobles S , Owouor DC , Padilla J , Sheth M , Wilson MM , Talarico S , Chen JC , Oberste MS , Batra D , McMullan LK , Halpin AL , Galloway SE , MacCannell DR , Kondor R , Barnes J , MacNeil A , Silk BJ , Dugan VG , Scobie HM , Wentworth DE . MMWR Morb Mortal Wkly Rep 2022 71 (6) 206-211 Genomic surveillance is a critical tool for tracking emerging variants of SARS-CoV-2 (the virus that causes COVID-19), which can exhibit characteristics that potentially affect public health and clinical interventions, including increased transmissibility, illness severity, and capacity for immune escape. During June 2021-January 2022, CDC expanded genomic surveillance data sources to incorporate sequence data from public repositories to produce weighted estimates of variant proportions at the jurisdiction level and refined analytic methods to enhance the timeliness and accuracy of national and regional variant proportion estimates. These changes also allowed for more comprehensive variant proportion estimation at the jurisdictional level (i.e., U.S. state, district, territory, and freely associated state). The data in this report are a summary of findings of recent proportions of circulating variants that are updated weekly on CDC's COVID Data Tracker website to enable timely public health action.(†) The SARS-CoV-2 Delta (B.1.617.2 and AY sublineages) variant rose from 1% to >50% of viral lineages circulating nationally during 8 weeks, from May 1-June 26, 2021. Delta-associated infections remained predominant until being rapidly overtaken by infections associated with the Omicron (B.1.1.529 and BA sublineages) variant in December 2021, when Omicron increased from 1% to >50% of circulating viral lineages during a 2-week period. As of the week ending January 22, 2022, Omicron was estimated to account for 99.2% (95% CI = 99.0%-99.5%) of SARS-CoV-2 infections nationwide, and Delta for 0.7% (95% CI = 0.5%-1.0%). The dynamic landscape of SARS-CoV-2 variants in 2021, including Delta- and Omicron-driven resurgences of SARS-CoV-2 transmission across the United States, underscores the importance of robust genomic surveillance efforts to inform public health planning and practice. |
Heterogeneous Ribonucleoprotein A1 (hnRNPA1) Interacts with the Nucleoprotein of the Influenza a Virus and Impedes Virus Replication.
Kaur R , Batra J , Stuchlik O , Reed MS , Pohl J , Sambhara S , Lal SK . Viruses 2022 14 (2) Influenza A virus (IAV), like other viruses, depends on the host cellular machinery for replication and production of progeny. The relationship between a virus and a host is complex, shaped by many spatial and temporal interactions between viral and host proteome, ultimately dictating disease outcome. Therefore, it is imperative to identify host-virus interactions as crucial determinants of disease pathogenies. Heterogeneous ribonucleoprotein A1 (hnRNPA1) is an RNA binding protein involved in the life cycle of many DNA and RNA viruses; however, its role in IAV remains undiscovered. Here we report that human hnRNPA1 physically interacts with the nucleoprotein (NP) of IAV in mammalian cells at different time points of the viral replication cycle. Temporal distribution studies identify hnRNPA1 and NP co-localize in the same cellular milieu in both nucleus and mitochondria in NP-transfected and IAV-infected mammalian cells. Interestingly, hnRNPA1 influenced NP gene expression and affected viral replication. Most importantly, hnRNPA1 knockdown caused a significant increase in NP expression and enhanced viral replication (93.82%) in IAV infected A549 cells. Conversely, hnRNPA1 overexpression reduced NP expression at the mRNA and protein levels and impeded virus replication by (60.70%), suggesting antagonistic function. Taken together, results from this study demonstrate that cellular hnRNPA1 plays a protective role in the host hitherto unknown and may hold potential as an antiviral target to develop host-based therapeutics against IAV. © 2022 by the authors. Licensee MDPI, Basel, Switzerland. |
Analysis of the initial lot of the CDC 2019-Novel Coronavirus (2019-nCoV) real-time RT-PCR diagnostic panel.
Lee JS , Goldstein JM , Moon JL , Herzegh O , Bagarozzi DAJr , Oberste MS , Hughes H , Bedi K , Gerard D , Cameron B , Benton C , Chida A , Ahmad A , Petway DJJr , Tang X , Sulaiman N , Teklu D , Batra D , Howard D , Sheth M , Kuhnert W , Bialek SR , Hutson CL , Pohl J , Carroll DS . PLoS One 2021 16 (12) e0260487 At the start of the COVID-19 pandemic, the Centers for Disease Control and Prevention (CDC) designed, manufactured, and distributed the CDC 2019-Novel Coronavirus (2019-nCoV) Real-Time RT-PCR Diagnostic Panel for SARS-CoV-2 detection. The diagnostic panel targeted three viral nucleocapsid gene loci (N1, N2, and N3 primers and probes) to maximize sensitivity and to provide redundancy for virus detection if mutations occurred. After the first distribution of the diagnostic panel, state public health laboratories reported fluorescent signal in the absence of viral template (false-positive reactivity) for the N3 component and to a lesser extent for N1. This report describes the findings of an internal investigation conducted by the CDC to identify the cause(s) of the N1 and N3 false-positive reactivity. For N1, results demonstrate that contamination with a synthetic template, that occurred while the "bulk" manufactured materials were located in a research lab for quality assessment, was the cause of false reactivity in the first lot. Base pairing between the 3' end of the N3 probe and the 3' end of the N3 reverse primer led to amplification of duplex and larger molecules resulting in false reactivity in the N3 assay component. We conclude that flaws in both assay design and handling of the "bulk" material, caused the problems with the first lot of the 2019-nCoV Real-Time RT-PCR Diagnostic Panel. In addition, within this study, we found that the age of the examined diagnostic panel reagents increases the frequency of false positive results for N3. We discuss these findings in the context of improvements to quality control, quality assurance, and assay validation practices that have since been improved at the CDC. |
Comparative genomic analysis of clinical Candida glabrata isolates identifies multiple polymorphic loci that can improve existing multilocus sequence typing strategy.
Arastehfar A , Marcet-Houben M , Daneshnia F , Taj-Aldeen SJ , Batra D , Lockhart SR , Shor E , Gabaldón T , Perlin DS . Stud Mycol 2021 100 100133 Candida glabrata is the second leading cause of candidemia in many countries and is one of the most concerning yeast species of nosocomial importance due to its increasing rate of antifungal drug resistance and emerging multidrug-resistant isolates. Application of multilocus sequence typing (MLST) to clinical C. glabrata isolates revealed an association of certain sequence types (STs) with drug resistance and mortality. The current C. glabrata MLST scheme is based on single nucleotide polymorphisms (SNPs) at six loci and is therefore relatively laborious and costly. Furthermore, only a few high-quality C. glabrata reference genomes are available, limiting rapid analysis of clinical isolates by whole genome sequencing. In this study we provide long-read based assemblies for seven additional clinical strains belonging to three different STs and use this information to simplify the C. glabrata MLST scheme. Specifically, a comparison of these genomes identified highly polymorphic loci (HPL) defined by frequent insertions and deletions (indels), two of which proved to be highly resolutive for ST. When challenged with 53 additional isolates, a combination of TRP1 (a component of the current MLST scheme) with either of the two HPL fully recapitulated ST identification. Therefore, our comparative genomic analysis identified a new typing approach combining SNPs and indels and based on only two loci, thus significantly simplifying ST identification in C. glabrata. Because typing tools are instrumental in addressing numerous clinical and biological questions, our new MLST scheme can be used for high throughput typing of C. glabrata in clinical and research settings. © 2021 The Authors |
Complete Genome Sequence of Rickettsia parkeri Strain Black Gap.
Karpathy SE , Paddock CD , Grizzard SL , Batra D , Rowe LA , Gauthier DT . Microbiol Resour Announc 2021 10 (44) e0062321 A unique genotype of Rickettsia parkeri, designated R. parkeri strain Black Gap, has thus far been associated exclusively with the North American tick, Dermacentor parumapertus. The compete genome consists of a single circular chromosome with 1,329,522 bp and a G+C content of 32.5%. |
Half Century Since SIDS: A Reappraisal of Terminology.
Shapiro-Mendoza CK , Palusci VJ , Hoffman B , Batra E , Yester M , Corey TS , Sens MA . Pediatrics 2021 148 (4) After a sudden infant death, parents and caregivers need accurate and open communication about why their infant died. Communicating tragic news about a child's death to families and caregivers is difficult. Shared and consistent terminology is essential for pediatricians, other physicians, and nonphysician clinicians to improve communication with families and among themselves. When families do not have complete information about why their child died, pediatricians will not be able to support them through the process and make appropriate referrals for pediatric specialty and mental health care. Families can only speculate about the cause and may blame themselves or others for the infant's death. The terminology used to describe infant deaths that occur suddenly and unexpectedly includes an assortment of terms that vary across and among pediatrician, other physician, or nonphysician clinician disciplines. Having consistent terminology is critical to improve the understanding of the etiology, pathophysiology, and epidemiology of these deaths and communicate with families. A lack of consistent terminology also makes it difficult to reliably monitor trends in mortality and hampers the ability to develop effective interventions. This report describes the history of sudden infant death terminology and summarizes the debate over the terminology and the resulting diagnostic shift of these deaths. This information is to assist pediatricians, other physicians, and nonphysician clinicians in caring for families during this difficult time. The importance of consistent terminology is outlined, followed by a summary of progress toward consensus. Recommendations for pediatricians, other physicians, and nonphysician clinicians are proposed. |
Complete Genome Sequence of Rhodococcus sp. Strain W8901, a Human Clinical Specimen, Assembled Using MiSeq and MinION Sequence Data.
Gulvik CA , Batra D , Howard DT , Sheth M , Humrighouse BW , Lee J , McQuiston JR , Lasker BA . Microbiol Resour Announc 2021 10 (35) e0061321 Rhodococcus sp. strain W8901 is a Gram-positive, aerobic, mycolic acid-containing coccobacillus obtained from a patient with acute lymphocytic leukemia. Here, we report on the complete, circular genome sequence obtained using Illumina MiSeq and Oxford Nanopore Technologies MinION reads in order to better resolve the phylogeny of a rare pathogen. |
Characterization of a novel transitional group Rickettsia species (Rickettsia tillamookensis sp. nov.) from the western black-legged tick, Ixodes pacificus.
Gauthier DT , Karpathy SE , Grizzard SL , Batra D , Rowe LA , Paddock CD . Int J Syst Evol Microbiol 2021 71 (7) A previously unrecognized Rickettsia species was isolated in 1976 from a pool of Ixodes pacificus ticks collected in 1967 from Tillamook County, Oregon, USA. The isolate produced low fever and mild scrotal oedema following intraperitoneal injection into male guinea pigs (Cavia porcellus). Subsequent serotyping characterized this isolate as distinct from recognized typhus and spotted fever group Rickettsia species; nonetheless, the isolate remained unevaluated by molecular techniques and was not identified to species level for the subsequent 30 years. Ixodes pacificus is the most frequently identified human-biting tick in the western United States, and as such, formal identification and characterization of this potentially pathogenic Rickettsia species is warranted. Whole-genome sequencing of the Tillamook isolate revealed a genome 1.43 Mbp in size with 32.4 mol% G+C content. Maximum-likelihood phylogeny of core proteins places it in the transitional group of Rickettsia basal to both Rickettsia felis and Rickettsia asembonensis. It is distinct from existing named species, with maximum average nucleotide identity of 95.1% to R. asembonensis and maximum digital DNA-DNA hybridization score similarity to R. felis at 80.1%. The closest similarity at the 16S rRNA gene (97.9%) and sca4 (97.5%/97.6% respectively) is to Candidatus 'Rickettsia senegalensis' and Rickettsia sp. cf9, both isolated from cat fleas (Ctenocephalides felis). We characterized growth at various temperatures and in multiple cell lines. The Tillamook isolate grows aerobically in Vero E6, RF/6A and DH82 cells, and growth is rapid at 28 °C and 32 °C. Using accepted genomic criteria, we propose the name Rickettsia tillamookensis sp. nov., with the type strain Tillamook 23. Strain Tillamook 23 is available from the Centers for Disease Control and Prevention Rickettsial Isolate Reference Collection (WDCM 1093), Atlanta, GA, USA (CRIRC accession number RTI001(T)) and the Collection de Souches de l'Unité des Rickettsies (WDCM 875), Marseille, France (CSUR accession number R5043). Using accepted genomic criteria, we propose the name Rickettsia tillamookensis sp. nov., with the type strain Tillamook 23 (=CRIRC RTI001=R5043). |
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. |
Chromosome-Level Genome Sequence of Leishmania (Leishmania) tropica Strain CDC216-162, Isolated from an Afghanistan Clinical Case.
Unoarumhi Y , Batra D , Sheth M , Narayanan V , Lin W , Zheng Y , Rowe LA , Pohl J , de Almeida M . Microbiol Resour Announc 2021 10 (20) PacBio and Illumina MiSeq platforms were used for genomic sequencing of a Leishmania (Leishmania) tropica strain isolated from a patient infected in Pakistan. PacBio assemblies were generated using Flye v2.4 and polished with MiSeq data. The results represent a considerable improvement of the currently available genome sequences in the GenBank database. |
Cutaneous Leishmaniasis Caused by an Unknown Leishmania Strain, Arizona, USA
de Almeida M , Zheng Y , Nascimento FS , Bishop H , Cama VA , Batra D , Unoarumhi Y , Afghan AK , Shi VY , LeBoit PE , Liu EW , Donovan FM . Emerg Infect Dis 2021 27 (6) 1714-1717 We investigated an autochthonous case of cutaneous leishmaniasis caused by a genetically different Leishmania sp. in a patient in Arizona, USA. This parasite was classified into the subgenus Leishmania on the basis of multilocus DNA sequence and phylogenetic analyses of the rRNA locus and 11 reference genes. |
Prevalent, protective, and convergent IgG recognition of SARS-CoV-2 non-RBD spike epitopes.
Voss WN , Hou YJ , Johnson NV , Delidakis G , Kim JE , Javanmardi K , Horton AP , Bartzoka F , Paresi CJ , Tanno Y , Chou CW , Abbasi SA , Pickens W , George K , Boutz DR , Towers DM , McDaniel JR , Billick D , Goike J , Rowe L , Batra D , Pohl J , Lee J , Gangappa S , Sambhara S , Gadush M , Wang N , Person MD , Iverson BL , Gollihar JD , Dye J , Herbert A , Finkelstein IJ , Baric RS , McLellan JS , Georgiou G , Lavinder JJ , Ippolito GC . Science 2021 372 (6546) 1108-1112 The molecular composition and binding epitopes of the immunoglobulin G (IgG) antibodies that circulate in blood plasma following SARS-CoV-2 infection are unknown. Proteomic deconvolution of the IgG repertoire to the spike glycoprotein in convalescent subjects revealed that the response is directed predominantly (>80%) against epitopes residing outside the receptor-binding domain (RBD). In one subject, just four IgG lineages accounted for 93.5% of the response, including an N-terminal domain (NTD)-directed antibody that was protective against lethal viral challenge. Genetic, structural, and functional characterization of a multi-donor class of "public" antibodies revealed an NTD epitope that is recurrently mutated among emerging SARS-CoV-2 variants of concern. These data show that "public" NTD-directed and other non-RBD plasma antibodies are prevalent and have implications for SARS-CoV-2 protection and antibody escape. |
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