Emergence of novel strains of Shigella flexneri associated with sexual transmission in adult men in England, 2019-2020.
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ABSTRACT:
SUBMITTER: Dallman TJ
PROVIDER: S-EPMC8604172 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Since the 1970s, shigellosis has been reported as a sexually transmissible infection, and in recent years, genomic data have revealed the breadth of Shigella spp. transmission among global networks of men who have sex with men (MSM). In 2015, Public Health England (PHE) introduced routine whole-genome sequencing (WGS) of Shigella spp. to identify transmission clusters. However, limited behavioural information for the cases hampers interpretation. We investigated whether WGS can distinguish between clusters representing sexual transmission in MSM and clusters representing community (non-sexual) transmission to inform infection control. WGS data for Shigella flexneri from August 2015 to July 2017 were aggregated into single linkage clusters based on SNP typing using a range of SNP distances (the standard for Shigella surveillance at PHE is 10 SNPs). Clusters were classified as 'adult male', 'household', 'travel-associated' or 'community' using routine demographic data submitted alongside laboratory cultures. From August 2015 to March 2017, PHE contacted those with shigellosis as part of routine public-health follow-up and collected exposure data on a structured questionnaire, which for the first time included questions about sexual identity and behaviour. The questionnaire data were used to determine whether clusters classified as 'adult male' represented likely sexual transmission between men, thereby validating the use of the SNP clustering tool for informing appropriate public-health responses. Overall, 1006?S. flexneri cases were reported, of which 563 clustered with at least one other case (10-SNP threshold). Linked questionnaire data were available for 106 clustered cases, of which 84.0?% belonged to an 'adult male' cluster. At the 10-SNP threshold, 95.1?% [95?% confidence interval (CI) 88.0-98.1%] of MSM belonged to an 'adult male' cluster, while 73.2?% (95?% CI 49.1-87.5%) of non-MSM belonged to a 'community' or 'travel-associated' cluster. At the 25-SNP threshold, all MSM (95?%?CI 96.0-100%) belonged to an 'adult male' cluster and 77.8?% (95?% CI 59.2-89.4%) of non-MSM belonged to a 'community' or 'travel-associated' cluster. Within one phylogenetic clade of S. flexneri, 9 clusters were identified (7 'adult male'; 2 'community') using a 10-SNP threshold, while a single 'adult male' cluster was identified using a 25-SNP threshold. Genotypic markers of azithromycin resistance were detected in 84.5?% (294/348) of 'adult male' cases and 20.9?% (9/43) of cases in other clusters (10-SNP threshold), the latter of which contained gay-identifying men who reported recent same-sex sexual contact. Our study suggests that SNP clustering can be used to identify Shigella clusters representing likely sexual transmission in MSM to inform infection control. Defining clusters requires a flexible approach in terms of genetic relatedness to ensure a clear understanding of underlying transmission networks.
| S-EPMC6927305 | biostudies-literature
Project description:Shigellosis is an enteric infection that transmits through the faecal-oral route, which can occur during sex between men who have sex with men (MSM). Between 2009 and 2014, an epidemic of sexually transmissible Shigella flexneri 3a occurred in England that subsequently declined. However, from 2019 to 2021, despite SARS-CoV-2 restrictions, S. flexneri 3a continued to re-emerge. We explored possible drivers of re-emergence by comparing host demography and pathogen genomics. Cases were primarily among 35-64 year old men in London. Genomic analyses of 502 bacterial isolates showed that the majority (58%) of re-emerging MSM strains were a clonal replacement of the original, with reduced antimicrobial resistance, conservation of plasmid col156_1, and two SNPs with 19 predicted effects. The absence of major changes in the pathogen or host demographics suggest that other factors may have driven the re-emergence of S. flexneri 3a and highlight the need for further work in the area.
| S-EPMC11296952 | biostudies-literature
Project description:BackgroundSeveral countries have recently reported the detection of ESBL-producing Shigella sonnei associated with transmission among MSM. In a previous study by our group, 2.8% of Shigella spp. obtained from MSM in Barcelona between 2015 and 2019 were ESBL producers.ObjectivesTo describe and characterize the emerging ESBL-producing Shigella spp. associated with sexual transmission among MSM detected from 2020 to 2021 in Barcelona, elucidating their connectivity with contemporaneous ESBL-producing Shigella spp. from other countries.ResultsFrom 2020 to 2021, we identified that among MSM, 68% of S. sonnei were XDR harbouring blaCTX-M-27 and 14% of Shigella flexneri were MDR harbouring blaCTX-M-27. WGS analysis showed that the ESBL-producing S. sonnei were part of a monophyletic cluster, which included isolates responsible for the prolonged outbreak occurring in the UK. Our data also reveal the first emergence and clonal dissemination of ESBL-producing and fluoroquinolone-resistant S. flexneri 2a among MSM.ConclusionsWe report an increasing trend of antimicrobial resistance in Shigella spp. among MSM in Barcelona since 2021, mainly as a consequence of the dissemination of XDR ESBL-producing S. sonnei, previously reported in the UK. These results highlight the importance of international collaborative surveillance of MDR/XDR S. sonnei and S. flexneri for rapid identification of their emergence and the prevention of the transmission of these pathogens.
| S-EPMC10068420 | biostudies-literature
Project description:We report an outbreak of azithromycin-nonsusceptible Shigella flexneri 3a infection in Taiwan associated with men who have sex with men. The bacterial strains belonged to the sublineage A of a recently reported outbreak lineage associated with men who have sex with men, characterized by reduced azithromycin susceptibility and circulation in shigellosis low-risk regions.
| S-EPMC5324798 | biostudies-literature
Project description:Background"Conversion therapy" practices (CTP) are organized and sustained efforts to avoid the adoption of non-heterosexual sexual orientations and/or of gender identities not assigned at birth. Few data are available to inform the contemporary prevalence of CTP. The aim of this study is to quantify the prevalence of CTP among Canadian sexual and gender minority men, including details regarding the setting, age of initiation, and duration of CTP exposure.MethodsSexual and gender minority men, including transmen and non-binary individuals, aged ≥ 15, living in Canada were recruited via social media and networking applications and websites, November 2019-February 2020. Participants provided demographic data and detailed information about their experiences with CTP.Results21% of respondents (N = 9,214) indicated that they or any person with authority (e.g., parent, caregiver) ever tried to change their sexual orientation or gender identity, and 10% had experienced CTP. CTP experience was highest among non-binary (20%) and transgender respondents (19%), those aged 15-19 years (13%), immigrants (15%), and racial/ethnic minorities (11-22%, with variability by identity). Among the n = 910 participants who experienced CTP, most experienced CTP in religious/faith-based settings (67%) or licensed healthcare provider offices (20%). 72% of those who experienced CTP first attended before the age of 20 years, 24% attended for one year or longer, and 31% attended more than five sessions.InterpretationCTP remains prevalent in Canada and is most prevalent among younger cohorts, transgender people, immigrants, and racial/ethnic minorities. Legislation, policy, and education are needed that target both religious and healthcare settings.
| S-EPMC8174694 | biostudies-literature
Project description:BACKGROUND: Shigella bacteria cause dysentery, which remains a significant threat to public health. Shigella flexneri is the most common species in both developing and developed countries. Five Shigella genomes have been sequenced, revealing dynamic and diverse features. To investigate the intra-species diversity of S. flexneri genomes further, we have sequenced the complete genome of S. flexneri 5b strain 8401 (abbreviated Sf8401) and compared it with S. flexneri 2a (Sf301). RESULTS: The Sf8401 chromosome is 4.5-Mb in size, a little smaller than that of Sf301, mainly because the former lacks the SHI-1 pathogenicity island (PAI). Compared with Sf301, there are 6 inversions and one translocation in Sf8401, which are probably mediated by insertion sequences (IS). There are clear differences in the known PAIs between these two genomes. The bacteriophage SfV segment remaining in SHI-O of Sf8401 is clearly larger than the remnants of bacteriophage SfII in Sf301. SHI-1 is absent from Sf8401 but a specific related protein is found next to the pheV locus. SHI-2 is involved in one intra-replichore inversion near the origin of replication, which may change the expression of iut/iuc genes. Moreover, genes related to the glycine-betaine biosynthesis pathway are present only in Sf8401 among the known Shigella genomes. CONCLUSION: Our data show that the two S. flexneri genomes are very similar, which suggests a high level of structural and functional conservation between the two serotypes. The differences reflect different selection pressures during evolution. The ancestor of S. flexneri probably acquired SHI-1 and SHI-2 before SHI-O was integrated and the serotypes diverged. SHI-1 was subsequently deleted from the S. flexneri 5b genome by recombination, but stabilized in the S. flexneri 2a genome. These events may have contributed to the differences in pathogenicity and epidemicity between the two serotypes of S. flexneri.
| S-EPMC1550401 | biostudies-literature
Project description:The public health value of whole genome sequencing (WGS) for Shigella spp. in England has been limited by a lack of information on sexual identity and behavior. We combined WGS data with other data sources to better understand Shigella flexneri transmission in men who have sex with men (MSM). WGS data for all S. flexneri isolates referred to the national reference laboratory were linked to i) clinical and behavioral data collected in seven of 21 health regions in England using a standardized exposure questionnaire and, ii) national HIV surveillance data. We included 926 S. flexneri isolates, of which 43.0% (n = 398) fell phylogenetically within two domestically circulating clades associated with genotypic markers of azithromycin resistance. Approximately one third of isolates in these clades were from people living with HIV, primarily acquired through sex between men. 182 (19.7%) isolates had linked questionnaire data; 88% (84/95) of MSM isolates fell phylogenetically within the domestically circulating clades, while 92% (72/78) of isolates from other cases fell within lineages linked with travel to high-risk regions. There was no evidence of sustained transmission between networks of MSM and the wider community. MSM were more likely to be admitted to hospital and receive antimicrobials. Our study emphasizes the importance of sex between men as a major route of transmission for S. flexneri. Combined WGS, epidemiological and clinical data provide unique insights that can inform contact tracing, clinical management and the delivery of targeted prevention activities. Future studies should investigate why MSM experience more severe clinical outcomes. IMPORTANCE Within the last 2 decades there have been an increasing number of Shigella spp. outbreaks among men who have sex with men (MSM) worldwide. In 2015, Public Health England (PHE) introduced routine whole genome sequencing (WGS) for the national surveillance of Shigella spp. However, the lack of information on sexual identity and behavior has hindered interpretation. Our study illustrates the power of linking WGS data with epidemiological, behavioral, and clinical data. We provide unique population-level insights into different transmission networks that can inform the delivery of appropriate public health interventions and patient management. Furthermore, we describe and compare clinical characteristics and outcomes of S. flexneri infection in MSM and other exposure groups. We found that MSM were more likely to be admitted to hospital and receive antimicrobials, indicating that their infections were potentially more severe. The exact reasons for this are unclear and require further exploration.
| S-EPMC8672885 | biostudies-literature
Project description:The instability of Shigella genomes has been described, but how this instability causes phenotypic differences within the Shigella flexneri species is largely unknown and likely variable. We describe herein the genome of S. flexneri strain PE577, originally a clinical isolate, which exhibits several phenotypic differences compared to the model strain 2457T. Like many previously described strains of S. flexneri, PE577 lacks discernible, functional CRISPR and restriction-modification systems. Its phenotypic differences when compared to 2457T include lower transformation efficiency, higher oxygen sensitivity, altered carbon metabolism, and greater susceptibility to a wide variety of lytic bacteriophage isolates. Since relatively few Shigella phages have been isolated on 2457T or the previously characterized strain M90T, developing a more universal model strain for isolating and studying Shigella phages is critical to understanding both phages and phage-host interactions. In addition to phage biology, the genome sequence of PE577 was used to generate and test hypotheses of how pseudogenes in this strain-whether interrupted by degraded prophages, transposases, frameshifts, or point mutations-have led to metabolic rewiring compared to the model strain 2457T. Results indicate that PE577 can utilise the less-efficient pyruvate oxidase/acetyl-CoA synthetase (PoxB/Acs) pathway to produce acetyl-CoA, while strain 2457T cannot due to a nonsense mutation in acs, rendering it a pseudogene in this strain. Both strains also utilize pyruvate-formate lyase to oxidize formate but cannot survive with this pathway alone, possibly because a component of the formate-hydrogen lyase (fdhF) is a pseudogene in both strains.Importance Shigella causes millions of dysentery cases worldwide, primarily affecting children under five years old. Despite active research in developing vaccines and new antibiotics, relatively little is known about the variation of physiology or metabolism across multiple isolates. In this work, we investigate two strains of S. flexneri that share 98.9% genetic identity but exhibit drastic differences in metabolism, ultimately affecting the growth of the two strains. Results suggest additional strains within the S. flexneri species utilize different metabolic pathways to process pyruvate. Metabolic differences between these closely-related isolates suggest an even wider variety of differences in growth across S. flexneri and Shigella in general. Exploring this variation further may assist the development or application of vaccines and therapeutics to combat Shigella infections.
| S-EPMC8117524 | biostudies-literature
Project description:Shigella spp. are the causative agent of shigellosis with Shigella flexneri serotype 2a being the most prevalent in developing countries. Epidemiological surveillance in China found that a new serotype of S. flexneri appeared in 2001 and replaced serotype 2a in 2003 as the most prevalent serotype in Henan Province. The new serotype also became the dominant serotype in 7 of the 10 other provinces under surveillance in China by 2007. The serotype was identified as a variant of serotype X. It differs from serotype X by agglutination to the monovalent anti-IV type antiserum and the group antigen-specific monoclonal antibody MASF IV-I. Genome sequencing of a serotype X variant isolate, 2002017, showed that it acquired a Shigella serotype conversion island, also as an SfX bacteriophage, containing gtr genes for type X-specific glucosylation. Multilocus sequence typing of 15 genes from 37 serotype X variant isolates and 69 isolates of eight other serotypes, 1a, 2a, 2b, 3a, 4a, 5b, X, and Y, found that all belong to a new sequence type (ST), ST91. Pulsed-field gel electrophoresis revealed 154 pulse types with 655 S. flexneri isolates analyzed and identified 57 serotype switching events. The data suggest that S. flexneri epidemics in China have been caused by a single epidemic clone, ST91, with frequent serotype switching to evade infection-induced immunity to serotypes to which the population was exposed previously. The clone has also acquired resistance to multiple antibiotics. These findings underscore the challenges to the current vaccine development and control strategies for shigellosis.
| S-EPMC2815595 | biostudies-literature
Project description:Shigella flexneri is a leading cause of bacterial dysentery in developing countries. Among the 15 known serotypes, four (1b, 3a, 3b and 4b) contain a group 6 epitope due to an acetyl group connected to the O-2 position of rhamnose III on the tetrasaccharide structure of the lipopolysaccharide. O-acetyltransferase encoded by a bacteriophage, Sf6, mediates the acetylation reaction. We found that the oac gene in serotype 1b strains was very different from that in serotypes 3a, 3b and 4b strains and is herein after referred to as oac 1b which shares with oac 88%-89% identity at the DNA level and 85% identity at the protein level. Considering that S. flexneri strains of serotypes 1-5 share a recent common ancestry, the divergent oac 1b is more likely to have been obtained from outside S. flexneri than to have undergone rapid divergence from the oac gene in the other serotypes (3a, 3b and 4b) within S. flexneri. The cloned oac 1b gene was found to perform the same acetylation function as oac. Analysis of the genomic regions flanking oac 1b showed that it was present in a prophage on the chromosome and the organizational structure is different from that of phage Sf6. Additionally, phage conversion assay showed that serotype 1b cannot be generated by infecting serotype 1a strains with Sf6. We conclude that oac 1b was carried by a non-Sf6 phage and is uniquely present in serotype 1b.
| S-EPMC3630932 | biostudies-literature