scholarly journals A multisite genomic epidemiology study of Clostridioides difficile infections in the U.S. supports differential roles of healthcare versus community spread for two common strains

2020 ◽  
Author(s):  
Arianna Miles-Jay ◽  
Vincent B. Young ◽  
Eric G. Pamer ◽  
Tor C. Savidge ◽  
Mini Kamboj ◽  
...  
Keyword(s):  
Phylogenetic Analyses ◽  
Clinical Care ◽  
Whole Genome Sequence ◽  
P Value ◽  
Whole Genome ◽  
Epidemiology Study ◽  
Genomic Epidemiology ◽  
Clostridioides Difficile ◽  
Healthcare Associated ◽  
The U.S

ABSTRACTClostridioides difficile is the leading cause of healthcare-associated infectious diarrhea. However, it is increasingly appreciated that healthcare-associated infections derive from both community and healthcare transmission, and that the primary sites of C. difficile transmission may be strain dependent. We conducted a multisite genomic epidemiology study to assess differential genomic evidence of healthcare vs. community spread for two of the most common C. difficile strains in the U.S.: sequence type (ST) 1 (associated with Ribotype 027) and ST2 (associated with Ribotype 014/020). Isolates recovered from stool specimens collected during standard clinical care at three geographically distinct U.S. medical centers between 2010 and 2018 underwent whole genome sequencing and phylogenetic analyses. ST1 and ST2 isolates both displayed some evidence of phylogenetic clustering by study site, but clustering was stronger and more apparent in ST1, consistent with our healthcare-based study more comprehensively sampling local transmission of ST1 compared to ST2 strains. Analyses of pairwise single nucleotide variant (SNV) distance distributions were also consistent with more evidence of healthcare transmission of ST1 compared to ST2, with 44% of ST1 isolates being within 2 SNVs of another isolate from the same geographic collection site compared to 5.5% of ST2 isolates (p-value = <0.001). Conversely, ST2 isolates were more likely to have close genetic neighbors across disparate geographic sites compared to ST1 isolates, further supporting non-healthcare routes of spread for ST2 and highlighting the potential for misattributing genomic similarity among ST2 isolates to recent healthcare transmission. Finally, we estimated a lower evolutionary rate for the ST2 lineage compared to the ST1 lineage using Bayesian timed phylogenomic analyses, and hypothesize that this may contribute to observed differences in geographic concordance among closely related isolates. Together, these findings suggest that ST1 and ST2, while both common causes of C. difficile infection in hospitals, show differential reliance on community and hospital spread. This conclusion supports the need for strain-specific criteria for interpreting genomic linkages and emphasizes the importance of considering differences in the epidemiology of circulating strains when devising interventions to reduce the burden of C. difficile infections.DATA SUMMARYAll whole genome sequence data was uploaded to the National Center for Biotechnology Information (NCBI) Sequence Read Archive (SRA) under Bioproject accessions PRJNA595724, PRJNA561087, and PRJNA594943. Metadata that comply with patient privacy rules are included in the Supplementary Materials.

scholarly journals A multisite genomic epidemiology study of Clostridioides difficile infections in the USA supports differential roles of healthcare versus community spread for two common strains

2021 ◽  
Vol 7 (6) ◽  
Author(s):  
Arianna Miles-Jay ◽  
Vincent B. Young ◽  
Eric G. Pamer ◽  
Tor C. Savidge ◽  
Mini Kamboj ◽  
...  
Keyword(s):  
Type Species ◽  
Phylogenetic Analyses ◽  
Clinical Care ◽  
Epidemiology Study ◽  
Content Type ◽  
Genomic Epidemiology ◽  
Link Type ◽  
Clostridioides Difficile ◽  
The Usa ◽  
Healthcare Associated

Clostridioides difficile is the leading cause of healthcare-associated infectious diarrhoea. However, it is increasingly appreciated that healthcare-associated infections derive from both community and healthcare environments, and that the primary sites of C. difficile transmission may be strain-dependent. We conducted a multisite genomic epidemiology study to assess differential genomic evidence of healthcare vs community spread for two of the most common C. difficile strains in the USA: sequence type (ST) 1 (associated with ribotype 027) and ST2 (associated with ribotype 014/020). We performed whole-genome sequencing and phylogenetic analyses on 382 ST1 and ST2 C. difficile isolates recovered from stool specimens collected during standard clinical care at 3 geographically distinct US medical centres between 2010 and 2017. ST1 and ST2 isolates both displayed some evidence of phylogenetic clustering by study site, but clustering was stronger and more apparent in ST1, consistent with our healthcare-based study more comprehensively sampling local transmission of ST1 compared to ST2 strains. Analyses of pairwise single-nucleotide variant (SNV) distance distributions were also consistent with more evidence of healthcare transmission of ST1 compared to ST2, with 44 % of ST1 isolates being within two SNVs of another isolate from the same geographical collection site compared to 5.5 % of ST2 isolates (P-value=<0.001). Conversely, ST2 isolates were more likely to have close genetic neighbours across disparate geographical sites compared to ST1 isolates, further supporting non-healthcare routes of spread for ST2 and highlighting the potential for misattributing genomic similarity among ST2 isolates to recent healthcare transmission. Finally, we estimated a lower evolutionary rate for the ST2 lineage compared to the ST1 lineage using Bayesian timed phylogenomic analyses, and hypothesize that this may contribute to observed differences in geographical concordance among closely related isolates. Together, these findings suggest that ST1 and ST2, while both common causes of C. difficile infection in hospitals, show differential reliance on community and hospital spread. This conclusion supports the need for strain-specific criteria for interpreting genomic linkages and emphasizes the importance of considering differences in the epidemiology of circulating strains when devising interventions to reduce the burden of C. difficile infections.

scholarly journals Phylogenetic and genetic characterization of Treponema pallidum strains from syphilis patients in Japan by whole-genome sequence analysis from global perspectives

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shingo Nishiki ◽  
Kenichi Lee ◽  
Mizue Kanai ◽  
Shu-ichi Nakayama ◽  
Makoto Ohnishi
Keyword(s):  
Genetic Difference ◽  
Phylogenetic Analyses ◽  
Treponema Pallidum ◽  
Whole Genome Sequence ◽  
Epidemiological Surveillance ◽  
Recent Common Ancestor ◽  
Whole Genome ◽  
Global Perspectives ◽  
Most Recent Common Ancestor ◽  
Sex With Men

AbstractJapan has had a substantial increase in syphilis cases since 2013. However, research on the genomic features of the Treponema pallidum subspecies pallidum (TPA) strains from these cases has been limited. Here, we elucidated the genetic variations and relationships between TPA strains in Japan (detected between 2014 and 2018) and other countries by whole-genome sequencing and phylogenetic analyses, including syphilis epidemiological surveillance data and information on patient sexual orientation. Seventeen of the 20 strains in Japan were SS14- and the remaining 3 were Nichols-lineage. Sixteen of the 17 SS14-lineage strains were classified into previously reported Sub-lineage 1B. Sub-lineage 1B strains in Japan have formed distinct sub-clusters of strains from heterosexuals and strains from men who have sex with men. These strains were closely related to reported TPA strains in China, forming an East-Asian cluster. However, those strains in these countries evolved independently after diverging from their most recent common ancestor and expanded their genetic diversity during the time of syphilis outbreak in each country. The genetic difference between the TPA strains in these countries was characterized by single-nucleotide-polymorphism analyses of their penicillin binding protein genes. Taken together, our results elucidated the detailed phylogenetic features and transmission networks of syphilis.

scholarly journals Are Many Patients Diagnosed With Healthcare-associated Clostridioides difficile Infections Colonized With the Infecting Strain on Admission?

2019 ◽  
Vol 69 (10) ◽  
pp. 1801-1804 ◽  
Author(s):  
Melany Gonzalez-Orta ◽  
Carlos Saldana ◽  
Yilen Ng-Wong ◽  
Jennifer Cadnum ◽  
Annette Jencson ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Acute Care ◽  
Genome Sequencing ◽  
Acute Care Hospital ◽  
Whole Genome ◽  
Care Hospital ◽  
Clostridioides Difficile ◽  
Healthcare Associated

Abstract In a cohort of 480 patients admitted to an acute care hospital, 68 (14%) had positive perirectal cultures for toxigenic Clostridioides difficile on admission. Of the 11 patients (2%) diagnosed with healthcare-associated C. difficile infections, 3 (27%) had genetically related admission and infection isolates, based on whole-genome sequencing.

scholarly journals Genomic Epidemiology of the Haitian Cholera Outbreak: a Single Introduction Followed by Rapid, Extensive, and Continued Spread Characterized the Onset of the Epidemic

mBio ◽  
2014 ◽  
Vol 5 (6) ◽  
Author(s):  
Mark Eppinger ◽  
Talima Pearson ◽  
Sara S. K. Koenig ◽  
Ofori Pearson ◽  
Nathan Hicks ◽  
...  
Keyword(s):  
Vibrio Cholerae ◽  
Whole Genome Sequence ◽  
Epidemiological Surveillance ◽  
Molecular Evidence ◽  
Whole Genome ◽  
Cholera Outbreak ◽  
Content Type ◽  
Genomic Epidemiology ◽  
Southern Asia ◽  
Strain Collection

ABSTRACT For centuries, cholera has been one of the most feared diseases. The causative agent Vibrio cholerae is a waterborne Gram-negative enteric pathogen eliciting a severe watery diarrheal disease. In October 2010, the seventh pandemic reached Haiti, a country that had not experienced cholera for more than a century. By using whole-genome sequence typing and mapping strategies of 116 serotype O1 strains from global sources, including 44 Haitian genomes, we present a detailed reconstructed evolutionary history of the seventh pandemic with a focus on the Haitian outbreak. We catalogued subtle genomic alterations at the nucleotide level in the genome core and architectural rearrangements from whole-genome map comparisons. Isolates closely related to the Haitian isolates caused several recent outbreaks in southern Asia. This study provides evidence for a single-source introduction of cholera from Nepal into Haiti followed by rapid, extensive, and continued clonal expansion. The phylogeographic patterns in both southern Asia and Haiti argue for the rapid dissemination of V. cholerae across the landscape necessitating real-time surveillance efforts to complement the whole-genome epidemiological analysis. As eradication efforts move forward, phylogeographic knowledge will be important for identifying persistent sources and monitoring success at regional levels. The results of molecular and epidemiological analyses of this outbreak suggest that an indigenous Haitian source of V. cholerae is unlikely and that an indigenous source has not contributed to the genomic evolution of this clade. IMPORTANCE In this genomic epidemiology study, we have applied high-resolution whole-genome-based sequence typing methodologies on a comprehensive set of genome sequences that have become available in the aftermath of the Haitian cholera epidemic. These sequence resources enabled us to reassess the degree of genomic heterogeneity within the Vibrio cholerae O1 serotype and to refine boundaries and evolutionary relationships. The established phylogenomic framework showed how outbreak isolates fit into the global phylogeographic patterns compared to a comprehensive globally and temporally diverse strain collection and provides strong molecular evidence that points to a nonindigenous source of the 2010 Haitian cholera outbreak and refines epidemiological standards used in outbreak investigations for outbreak inclusion/exclusion following the concept of genomic epidemiology. The generated phylogenomic data have major public health relevance in translating sequence-based information to assist in future diagnostic, epidemiological, surveillance, and forensic studies of cholera.

scholarly journals Epidemic Clostridioides difficile Ribotype 027 Lineages: Comparisons of Texas Versus Worldwide Strains

2019 ◽  
Vol 6 (2) ◽  
Author(s):  
Bradley T Endres ◽  
Khurshida Begum ◽  
Hua Sun ◽  
Seth T Walk ◽  
Ali Memariani ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Phylogenetic Trees ◽  
Large Scale ◽  
The United States ◽  
Whole Genome Sequence ◽  
Snp Analysis ◽  
Whole Genome ◽  
Ribotype 027 ◽  
Clostridioides Difficile

Abstract Background The epidemic Clostridioides difficile ribotype 027 strain resulted from the dissemination of 2 separate fluoroquinolone-resistant lineages: FQR1 and FQR2. Both lineages were reported to originate in North America; however, confirmatory large-scale investigations of C difficile ribotype 027 epidemiology using whole genome sequencing has not been undertaken in the United States. Methods Whole genome sequencing and single-nucleotide polymorphism (SNP) analysis was performed on 76 clinical ribotype 027 isolates obtained from hospitalized patients in Texas with C difficile infection and compared with 32 previously sequenced worldwide strains. Maximum-likelihood phylogeny based on a set of core genome SNPs was used to construct phylogenetic trees investigating strain macro- and microevolution. Bayesian phylogenetic and phylogeographic analyses were used to incorporate temporal and geographic variables with the SNP strain analysis. Results Whole genome sequence analysis identified 2841 SNPs including 900 nonsynonymous mutations, 1404 synonymous substitutions, and 537 intergenic changes. Phylogenetic analysis separated the strains into 2 prominent groups, which grossly differed by 28 SNPs: the FQR1 and FQR2 lineages. Five isolates were identified as pre-epidemic strains. Phylogeny demonstrated unique clustering and resistance genes in Texas strains indicating that spatiotemporal bias has defined the microevolution of ribotype 027 genetics. Conclusions Clostridioides difficile ribotype 027 lineages emerged earlier than previously reported, coinciding with increased use of fluoroquinolones. Both FQR1 and FQR2 ribotype 027 epidemic lineages are present in Texas, but they have evolved geographically to represent region-specific public health threats.

scholarly journals Genomic analysis of Clostridioides difficile in two regions reveals a diversity of strains and limited transmission

2020 ◽  
Vol 41 (S1) ◽  
pp. s237-s238
Author(s):  
Nicole Pecora ◽  
Stacy Holzbauer ◽  
Xiong Wang ◽  
Yu Gu ◽  
Trupti Hatwar ◽  
...  
Keyword(s):  
New York ◽  
Genomic Analysis ◽  
Illumina Miseq ◽  
The United States ◽  
Snp Analysis ◽  
Whole Genome ◽  
Emerging Infections ◽  
Clostridioides Difficile ◽  
Healthcare Associated ◽  
Incident Cases

Background: The epidemic NAP1/027 Clostridioides difficile strain (MLST1, ST1) that emerged in the mid-2000 is on the decline. The current distribution of C. difficile strain types and their transmission dynamics are poorly defined. We performed whole-genome sequencing (WGS) of C. difficile isolates in 2 regions to identify the predominant multilocus sequence types (MLSTs) in community- and healthcare-associated cases and potential transmission between cases using whole-genome single-nucleotide polymorphism (SNP) analysis. Methods: Isolates were collected through the CDC Emerging Infections Program population-based surveillance for C. difficile infections (CDI) for 3 months between 2016 and 2017 in 5 Minnesota counties and 1 New York county. Isolates were limited to incident cases (CDI in a county resident with no positive C. difficile test in the preceding 8 weeks). Cases were classified as healthcare associated (HA-CDI) or community associated (CA-CDI) based on healthcare exposures as previously described. WGS was performed on an Illumina Miseq. The CFSAN (FDA) pipeline was used to compute whole-genome SNPs, SPAdes was used for assembly, and MLST was assigned according to www.pubmlst.org. Results: Of 431 isolates, 269 originated from New York and 162 from Minnesota; 203 cases were classified as CA-CDI and 221 as HA-CDI. The proportion of CA-CDI cases was higher in Minnesota than in New York: 62% vs 38%. The predominant MLSTs across both sites were ST42 (9%), ST8 (8%), and ST2 (8%). MLSTs more frequently encountered in HA-CDI than CA-CDI included ST1 (note that this ST includes PCR Ribotype 027; 76% HA-CDI), ST53 (84% HA-CDI), and ST43 (80% HA-CDI). In contrast, ST110 (63% CA-CDI) and ST3 (67% CA-CDI) were more commonly isolated from CA-CDI cases. ST1 accounted for 7.6% of circulating strains and was more common in New York than Minnesota (10% vs 3%) and was concentrated among New York HA-CDI cases. Also, 412 isolates (1 per patient) were included in the final whole-genome SNP analysis. Of these, only 12 pairs were separated by 0–3 SNPs, indicating potential transmission, and most involved HA-CDI cases. ST1, ST17, and ST46 accounted for 8 of 12 pairs, with ST17 and ST46 potentially forming small clusters. Conclusions: This analysis provides a snapshot of the current genomic epidemiology of C. difficile across 2 geographically and epidemiologically distinct regions of the United States and supports other studies suggesting that the role of direct transmission in the spread of CDI may be limited.Funding: NoneDisclosures: None

scholarly journals Anin silicosurvey ofClostridioides difficileextrachromosomal elements

2019 ◽  
Author(s):  
Bastian Hornung ◽  
Ed J. Kuijper ◽  
Wiep Klaas Smits
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
In Silico ◽  
Sequence Data ◽  
Whole Genome ◽  
Clostridioides Difficile ◽  
Extrachromosomal Elements ◽  
European Nucleotide Archive ◽  
Healthcare Associated ◽  
Systematic Identification

AbstractThe gram-positive enteropathogenClostridioides difficileis the major cause of healthcare associated diarrhoea and is also an important cause of community-acquired infectious diarrhoea. Considering the burden of the disease, many studies have employed whole genome sequencing to identify factors that contribute to virulence and pathogenesis. Though extrachromosomal elements such as plasmids are important for these processes in other bacteria, the few characterized plasmids ofC. difficilehave no relevant functions assigned and no systematic identification of plasmids has been carried out to date. Here, we perform anin silicoanalysis of publicly available sequence data, to show that ∼13% of allC. difficilestrains contain extrachromosomal elements, with 1-6 elements per strain. Our approach identifies known plasmids (e.g. pCD6, pCD630 and cloning plasmids) and 6 novel putative plasmid families. Our study shows that plasmids are abundant and may encode functions that are relevant forC. difficilephysiology. The newly identified plasmids may also form the basis for the construction of novel cloning plasmids forC. difficilethat are compatible with existing tools.RepositoriesThe assembled circular type plasmids have been deposited at the European Nucleotide Archive (ENA) under accession numbers ERZ940801 and ERZ940803-ERZ940808.

scholarly journals Whole genome sequencing detects minimal clustering among Escherichia coli Sequence Type 131 H30 isolates collected from U.S. children’s hospitals

2019 ◽  
Author(s):  
Arianna Miles-Jay ◽  
Scott J. Weissmann ◽  
Amanda L. Adler ◽  
Janet G. Baseman ◽  
Danielle M. Zerr
Keyword(s):  
Escherichia Coli ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Sequence Type ◽  
Whole Genome ◽  
E Coli ◽  
Geographic Clustering ◽  
Healthcare Associated ◽  
The U.S ◽  
Hospital Transmission

AbstractEscherichia coli sequence type 131 H30 has garnered global attention as a dominant antimicrobial-resistant lineage of extraintestinal pathogenic E. coli, but its transmission dynamics remain undefined. We applied whole genome sequencing to identify putative transmission clusters among clinical isolates of H30 from children across the U.S. Of 126 isolates, 17 were involved in 8 putative transmission clusters; 4 clusters involved isolates with some evidence of healthcare-associated epidemiologic linkages. Geographic clustering analyses showed weak geographic clustering. These findings are consistent with a framework where within-hospital transmission is not a main contributor to the propagation of H30 in a pediatric setting.

scholarly journals Whole-Genome Sequencing Reveals the High Nosocomial Transmission and Antimicrobial Resistance of Clostridioides difficile in a Single Center in China, a Four-Year Retrospective Study

2022 ◽  
Author(s):  
Xin Wen ◽  
Cong Shen ◽  
Jinyu Xia ◽  
Lan-Lan Zhong ◽  
Zhongwen Wu ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Antimicrobial Resistance ◽  
Genome Sequencing ◽  
Whole Genome ◽  
Single Center ◽  
Content Type ◽  
The Past ◽  
Clostridioides Difficile ◽  
Healthcare Associated ◽  
Multiple Antibiotics

Clostridioides difficile infections (CDI) are the leading cause of healthcare-associated diarrhea and are known to be resistant to multiple antibiotics. In the past decade, C. difficile has emerged rapidly and has spread globally, causing great concern among American and European countries.

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