RESUMO
Shigella represents a paraphyletic group of enteroinvasive Escherichia coli. More than 40 Shigella serotypes have been reported. However, most cases within the men who have sex with men (MSM) community are attributed to 3 serotypes: Shigella sonnei unique serotype and Shigella flexneri 2a and 3a serotypes. Using the zebrafish model, we demonstrate that Shigella can establish persistent infection in vivo. Bacteria are not cleared by the immune system and become antibiotic tolerant. Establishment of persistent infection depends on the O-antigen, a key constituent of the bacterial surface and a serotype determinant. Representative isolates associated with MSM transmission persist in zebrafish, while representative isolates of a serotype not associated with MSM transmission do not. Isolates of a Shigella serotype establishing persistent infections elicited significantly less macrophage death in vivo than isolates of a serotype unable to persist. We conclude that zebrafish are a valuable platform to illuminate factors underlying establishment of Shigella persistent infection in humans.
Assuntos
Disenteria Bacilar , Minorias Sexuais e de Gênero , Shigella , Humanos , Masculino , Animais , Peixe-Zebra , Sorogrupo , Homossexualidade Masculina , Infecção Persistente , Disenteria Bacilar/microbiologia , Shigella flexneriRESUMO
Alphaproteobacteria include organisms living in close association with plants or animals. This interaction relies partly on orthologous two-component regulatory systems (TCS), with sensor and regulator proteins modulating the expression of conserved genes related to symbiosis/virulence. We assessed the ability of the exoS+Sm gene, encoding a sensor protein from the plant endosymbiont Sinorhizobium meliloti to substitute its orthologous bvrS in the related animal/human pathogen Brucella abortus. ExoS phosphorylated the B. abortus regulator BvrR in vitro and in cultured bacteria, showing conserved biological function. Production of ExoS in a B. abortus bvrS mutant reestablished replication in host cells and the capacity to infect mice. Bacterial outer membrane properties, the production of the type IV secretion system VirB, and its transcriptional regulators VjbR and BvrR were restored as compared to parental B. abortus. These results indicate that conserved traits of orthologous TCS from bacteria living in and sensing different environments are sufficient to achieve phenotypic plasticity and support bacterial survival. The knowledge of bacterial genetic networks regulating host interactions allows for an understanding of the subtle differences between symbiosis and parasitism. Rewiring these networks could provide new alternatives to control and prevent bacterial infection.
Assuntos
Brucella abortus , Genes Bacterianos , Animais , Camundongos , Humanos , Virulência/genética , Histidina Quinase/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Regulação Bacteriana da Expressão Gênica , Mamíferos/genética , Mamíferos/metabolismoRESUMO
Dissemination of antimicrobial resistance (AMR) genes by horizontal gene transfer (HGT) mediated through plasmids is a major global concern. Genomic epidemiology studies have shown varying success of different AMR plasmids during outbreaks, but the underlying reasons for these differences are unclear. Here, we investigated two Shigella plasmids (pKSR100 and pAPR100) that circulated in the same transmission network but had starkly contrasting epidemiological outcomes to identify plasmid features that may have contributed to the differences. We used plasmid comparative genomics to reveal divergence between the two plasmids in genes encoding AMR, SOS response alleviation and conjugation. Experimental analyses revealed that these genomic differences corresponded with reduced conjugation efficiencies for the epidemiologically successful pKSR100, but more extensive AMR, reduced fitness costs, and a reduced SOS response in the presence of antimicrobials, compared with the less successful pAPR100. The discrepant phenotypes between the two plasmids are consistent with the hypothesis that plasmid-associated phenotypes contribute to determining the epidemiological outcome of AMR HGT and suggest that phenotypes relevant in responding to antimicrobial pressure and fitness impact may be more important than those around conjugation in this setting. Plasmid phenotypes could thus be valuable tools in conjunction with genomic epidemiology for predicting AMR dissemination.
Assuntos
Farmacorresistência Bacteriana , Shigella , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana/genética , Transferência Genética Horizontal , Fenótipo , Plasmídeos , Shigella/genéticaRESUMO
Whole-genome sequencing has enhanced surveillance and facilitated detailed monitoring of the transmission of Shigella species in England. We undertook an epidemiological and phylogenetic analysis of isolates from all cases of shigellosis referred to Public Health England between 2015 and 2018 to explore recent strain characteristics and the transmission dynamics of Shigella species. Of the 4,950 confirmed cases of shigellosis identified during this period, the highest proportion of isolates was Shigella sonnei (54.4%), followed by S. flexneri (39.2%), S. boydii (4.1%), and S. dysenteriae (2.2%). Most cases were adults (82.9%) and male (59.5%), and 34.9% cases reported recent travel outside the United Kingdom. Throughout the study period, diagnoses of S. flexneri and S. sonnei infections were most common in men with no history of recent travel abroad. The species prevalence was not static, with cases of S. flexneri infection in men decreasing between 2015 and 2016 and the number of cases of S. sonnei infection increasing from 2017. Phylogenetic analysis showed this recent increase in S. sonnei infections was attributed to a novel clade that emerged from a Central Asia sublineage exhibiting resistance to ciprofloxacin and azithromycin. Despite changes in species prevalence, diagnoses of Shigella infections in England are persistently most common in adult males without a reported travel history, consistent with sexual transmission among men who have sex with men. The trend toward increasing rates of ciprofloxacin resistance in S. sonnei, in addition to plasmid-mediated azithromycin resistance, is of significant public health concern with respect to the transmission of multidrug-resistant gastrointestinal pathogens and the risk of treatment failures.
Assuntos
Disenteria Bacilar , Minorias Sexuais e de Gênero , Shigella , Adulto , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Disenteria Bacilar/epidemiologia , Inglaterra/epidemiologia , Feminino , Homossexualidade Masculina , Humanos , Masculino , Testes de Sensibilidade Microbiana , Filogenia , Shigella sonnei/genética , Reino UnidoRESUMO
In recent years nontyphoidal Salmonella has emerged as one of the pathogens most frequently isolated from the bloodstream in humans. Only a small group of Salmonella serovars cause this systemic infection, known as invasive nontyphoidal salmonellosis. Here, we present a focused minireview on Salmonella enterica serovar Panama, a serovar responsible for invasive salmonellosis worldwide. S Panama has been linked with infection of extraintestinal sites in humans, causing septicemia, meningitis, and osteomyelitis. The clinical picture is often complicated by antimicrobial resistance and has been associated with a large repertoire of transmission vehicles, including human feces and breast milk. Nonhuman sources of S Panama involve reptiles and environmental reservoirs, as well as food animals, such as pigs. The tendency of S Panama to cause invasive disease may be linked to certain serovar-specific genetic factors.
Assuntos
Infecções por Salmonella/microbiologia , Salmonella enterica/patogenicidade , Farmacorresistência Bacteriana Múltipla , Saúde Global , Humanos , Infecções por Salmonella/transmissão , Salmonella enterica/genética , VirulênciaRESUMO
Many pathogens that caused devastating disease throughout human history, such as Yersinia pestis, Mycobacterium tuberculosis, and Mycobacterium leprae, remain problematic today. Historical bacterial genomes represent a unique source of genetic information and advancements in sequencing technologies have allowed unprecedented insights from this previously understudied resource. This minireview brings together example studies which have utilized ancient DNA, individual historical isolates (both extant and dead) and collections of historical isolates. The studies span human history and highlight the contribution that sequencing and analysis of historical bacterial genomes have made to a wide variety of fields. From providing retrospective diagnosis, to uncovering epidemiological pathways and characterizing genetic diversity, there is clear evidence for the utility of historical isolate studies in understanding disease today. Studies utilizing historical isolate collections, such as those from the National Collection of Type Cultures, the American Type Culture Collection, and the Institut Pasteur, offer enhanced insight since they typically span a wide time period encompassing important historical events and are useful for the investigating the phylodynamics of pathogens. Furthermore, historical sequencing studies are particularly useful for looking into the evolution of antimicrobial resistance, a major public health concern. In summary, although there are limitations to working with historical bacterial isolates, especially when utilizing ancient DNA, continued improvement in molecular and sequencing technologies and the resourcefulness of investigators mean this area of study will continue to expand and contribute to the understanding of pathogens.
Assuntos
Bactérias/genética , DNA Antigo/análise , Genoma Bacteriano , Análise de Sequência de DNA , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Bactérias/patogenicidade , Farmacorresistência Bacteriana Múltipla/genética , Evolução Molecular , Variação Genética , Humanos , Mycobacterium leprae/genética , Mycobacterium leprae/patogenicidade , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/patogenicidade , Filogenia , Yersinia pestis/genética , Yersinia pestis/patogenicidadeRESUMO
Demodicosis is most frequently observed in the domestic dog (Canis familiaris), but it has rarely been reported in bats (Chiroptera). The overpopulation of Demodex spp. that causes dermatological changes is generally associated with a compromised immune system. We describe the gross and histological features of generalized demodicosis in an adult female African straw-coloured fruit bat (Eidolon helvum) drawn from a captive research colony. The histology of the lesions revealed comedones and follicular infundubular cysts harbouring numerous Demodex spp. mites, eliciting a minimal inflammatory response in the adjacent dermis. The histological examination of a full set of tissues did not reveal clear evidence of immunosuppression, although a clinical history of recent abortion and possible stressors due to captivity could be considered risk factors for the demodicosis. Attempts to determine the Demodex species using PCR on DNA extracted from the formalin fixed paraffin embedded tissue failed. This is the first clinical and histological description of demodicosis in Eidolon helvum.
Assuntos
Quirópteros , Infestações por Ácaros/veterinária , Ácaros/fisiologia , Animais , Animais de Zoológico/fisiologia , Diagnóstico Diferencial , Feminino , Gana , Infestações por Ácaros/diagnóstico , Infestações por Ácaros/parasitologia , Infestações por Ácaros/patologiaRESUMO
Several species of Brucella are known to be zoonotic, but B. neotomae infection has been thought to be limited to wood rats. In 2008 and 2011, however, B. neotomae was isolated from cerebrospinal fluid of 2 men with neurobrucellosis. The nonzoonotic status of B. neotomae should be reassessed.
Assuntos
Brucella/genética , Brucelose/epidemiologia , DNA Bacteriano/genética , Genoma Bacteriano , Zoonoses/epidemiologia , Animais , Arvicolinae/microbiologia , Brucella/classificação , Brucella/isolamento & purificação , Brucelose/diagnóstico , Brucelose/microbiologia , Costa Rica/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Filogenia , Zoonoses/microbiologiaRESUMO
Shigellae are sensitive indicator species for studying trends in the international transmission of antimicrobial-resistant Enterobacteriaceae. Orthodox Jewish communities (OJCs) are a known risk group for shigellosis; Shigella sonnei is cyclically epidemic in OJCs in Israel, and sporadic outbreaks occur in OJCs elsewhere. We generated whole-genome sequences for 437 isolates of S. sonnei from OJCs and non-OJCs collected over 22 years in Europe (the United Kingdom, France, and Belgium), the United States, Canada, and Israel and analyzed these within a known global genomic context. Through phylogenetic and genomic analysis, we showed that strains from outbreaks in OJCs outside of Israel are distinct from strains in the general population and relate to a single multidrug-resistant sublineage of S. sonnei that prevails in Israel. Further Bayesian phylogenetic analysis showed that this strain emerged approximately 30 years ago, demonstrating the speed at which antimicrobial drug-resistant pathogens can spread widely through geographically dispersed, but internationally connected, communities.
Assuntos
Antibacterianos/farmacologia , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/transmissão , Farmacorresistência Bacteriana Múltipla , Disenteria Bacilar/epidemiologia , Disenteria Bacilar/transmissão , Judeus , Shigella sonnei/efeitos dos fármacos , Viagem , Antibacterianos/uso terapêutico , Infecções Comunitárias Adquiridas/história , Infecções Comunitárias Adquiridas/microbiologia , Surtos de Doenças , Disenteria Bacilar/história , Disenteria Bacilar/microbiologia , Genes Bacterianos , Genoma Bacteriano , Saúde Global , História do Século XX , História do Século XXI , Humanos , Testes de Sensibilidade Microbiana , Vigilância da População , Fatores de Risco , Shigella sonnei/classificação , Shigella sonnei/genética , Shigella sonnei/isolamento & purificação , Sequenciamento Completo do GenomaRESUMO
The EGD Murray collection consists of approximately 500 clinical bacterial isolates, mainly Enterobacteriaceae, isolated from around the world between 1917 and 1949. A number of these "Murray" isolates have subsequently been identified as Klebsiella pneumoniae. Antimicrobial susceptibility testing of these isolates showed that over 30% were resistant to penicillins due to the presence of diverse blaSHV ß-lactamase genes. Analysis of susceptibility to skin antiseptics and triclosan showed that while the Murray isolates displayed a range of MIC/minimal bactericidal concentration (MBC) values, the mean MIC value was lower than that for more modern K. pneumoniae isolates tested. All Murray isolates contained the cation efflux gene cepA, which is involved in disinfectant resistance, but those that were more susceptible to chlorhexidine were found to have a 9- or 18-bp insertion in this gene. Susceptibility to other disinfectants, e.g., H2O2, in the Murray isolates was comparable to that in modern K. pneumoniae isolates. The Murray isolates were also less virulent in Galleria and had a different complement of putative virulence factors than the modern isolates, with the exception of an isolate related to the modern lineage CC23. More of the modern isolates (41% compared to 8%) are classified as good/very good biofilm formers, but there was overlap in the two populations. This study demonstrated that a significant proportion of the Murray Klebsiella isolates were resistant to penicillins before their routine use. This collection of pre-antibiotic era isolates may provide significant insights into adaptation in K. pneumoniae in relation to biocide susceptibility.
Assuntos
Antibacterianos/farmacologia , Desinfetantes/farmacologia , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/efeitos dos fármacos , Mariposas/microbiologia , Animais , Biofilmes/efeitos dos fármacos , Clorexidina/farmacologia , Humanos , Klebsiella pneumoniae/patogenicidade , Testes de Sensibilidade Microbiana , Mutagênese Insercional , Resistência às Penicilinas/efeitos dos fármacos , Triclosan/farmacologia , Fatores de Virulência , beta-Lactamases/genéticaRESUMO
BACKGROUND: Shigellosis (previously bacillary dysentery) was the primary diarrhoeal disease of World War 1, but outbreaks still occur in military operations, and shigellosis causes hundreds of thousands of deaths per year in developing nations. We aimed to generate a high-quality reference genome of the historical Shigella flexneri isolate NCTC1 and to examine the isolate for resistance to antimicrobials. METHODS: In this genomic analysis, we sequenced the oldest extant Shigella flexneri serotype 2a isolate using single-molecule real-time (SMRT) sequencing technology. Isolated from a soldier with dysentery from the British forces fighting on the Western Front in World War 1, this bacterium, NCTC1, was the first isolate accessioned into the National Collection of Type Cultures. We created a reference sequence for NCTC1, investigated the isolate for antimicrobial resistance, and undertook comparative genetics with S flexneri reference strains isolated during the 100 years since World War 1. FINDINGS: We discovered that NCTC1 belonged to a 2a lineage of S flexneri, with which it shares common characteristics and a large core genome. NCTC1 was resistant to penicillin and erythromycin, and contained a complement of chromosomal antimicrobial resistance genes similar to that of more recent isolates. Genomic islands gained in the S flexneri 2a lineage over time were predominately associated with additional antimicrobial resistances, virulence, and serotype conversion. INTERPRETATION: This S flexneri 2a lineage is a well adapted pathogen that has continued to respond to selective pressures. We have created a valuable historical benchmark for shigellae in the form of a high-quality reference sequence for a publicly available isolate. FUNDING: The Wellcome Trust.
Assuntos
Disenteria Bacilar/microbiologia , Genoma Bacteriano/genética , Shigella flexneri/genética , I Guerra Mundial , Anti-Infecciosos/farmacologia , Sequência de Bases , Farmacorresistência Bacteriana/genética , Disenteria Bacilar/tratamento farmacológico , Evolução Molecular , Humanos , Filogenia , Shigella flexneri/efeitos dos fármacosRESUMO
Bats carry a variety of paramyxoviruses that impact human and domestic animal health when spillover occurs. Recent studies have shown a great diversity of paramyxoviruses in an urban-roosting population of straw-colored fruit bats in Ghana. Here, we investigate this further through virus isolation and describe two novel rubulaviruses: Achimota virus 1 (AchPV1) and Achimota virus 2 (AchPV2). The viruses form a phylogenetic cluster with each other and other bat-derived rubulaviruses, such as Tuhoko viruses, Menangle virus, and Tioman virus. We developed AchPV1- and AchPV2-specific serological assays and found evidence of infection with both viruses in Eidolon helvum across sub-Saharan Africa and on islands in the Gulf of Guinea. Longitudinal sampling of E. helvum indicates virus persistence within fruit bat populations and suggests spread of AchPVs via horizontal transmission. We also detected possible serological evidence of human infection with AchPV2 in Ghana and Tanzania. It is likely that clinically significant zoonotic spillover of chiropteran paramyxoviruses could be missed throughout much of Africa where health surveillance and diagnostics are poor and comorbidities, such as infection with HIV or Plasmodium sp., are common.
Assuntos
Quirópteros/virologia , Infecções por Rubulavirus/veterinária , Infecções por Rubulavirus/virologia , Rubulavirus/classificação , Rubulavirus/isolamento & purificação , Zoonoses/epidemiologia , Adolescente , Adulto , África/epidemiologia , Animais , Anticorpos Antivirais/sangue , Criança , Pré-Escolar , Análise por Conglomerados , Feminino , Humanos , Lactente , Masculino , Dados de Sequência Molecular , Filogenia , RNA Viral/genética , Rubulavirus/genética , Rubulavirus/patogenicidade , Infecções por Rubulavirus/epidemiologia , Análise de Sequência de DNA , Estudos SoroepidemiológicosRESUMO
Bats host many viruses that are significant for human and domestic animal health, but the dynamics of these infections in their natural reservoir hosts remain poorly elucidated. In these, and other, systems, there is evidence that seasonal life-cycle events drive infection dynamics, directly impacting the risk of exposure to spillover hosts. Understanding these dynamics improves our ability to predict zoonotic spillover from the reservoir hosts. To this end, we followed henipavirus antibody levels of >100 individual E. helvum in a closed, captive, breeding population over a 30-month period, using a powerful novel antibody quantitation method. We demonstrate the presence of maternal antibodies in this system and accurately determine their longevity. We also present evidence of population-level persistence of viral infection and demonstrate periods of increased horizontal virus transmission associated with the pregnancy/lactation period. The novel findings of infection persistence and the effect of pregnancy on viral transmission, as well as an accurate quantitation of chiropteran maternal antiviral antibody half-life, provide fundamental baseline data for the continued study of viral infections in these important reservoir hosts.
Assuntos
Anticorpos Antivirais/sangue , Quirópteros , Infecções por Henipavirus/veterinária , Henipavirus/imunologia , Animais , Feminino , Gana , Infecções por Henipavirus/imunologia , Infecções por Henipavirus/virologia , Lactação , Estudos Longitudinais , Masculino , Gravidez , Estações do AnoRESUMO
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.
RESUMO
The constant arms race between bacteria and their parasites has resulted in a large diversity of bacterial defenses, with many bacteria carrying multiple systems. Here, we report the discovery of a phylogenetically widespread defense system, coined methylation-associated defense system (MADS), which is distributed across gram-positive and gram-negative bacteria. MADS interacts with a CRISPR-Cas system in its native host to provide robust and durable resistance against phages. While phages can acquire epigenetic-mediated resistance against MADS, co-existence of MADS and a CRISPR-Cas system limits escape emergence. MADS comprises eight genes with predicted nuclease, ATPase, kinase, and methyltransferase domains, most of which are essential for either self/non-self discrimination, DNA restriction, or both. The complex genetic architecture of MADS and MADS-like systems, relative to other prokaryotic defenses, points toward highly elaborate mechanisms of sensing infections, defense activation, and/or interference.
Assuntos
Bacteriófagos , Sistemas CRISPR-Cas , Bacteriófagos/genética , Bacteriófagos/fisiologia , Filogenia , Bactérias Gram-Negativas/genética , Bactérias Gram-Negativas/virologia , Bactérias/virologia , Bactérias/genética , Bactérias Gram-Positivas/genética , Bactérias Gram-Positivas/virologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , MetilaçãoRESUMO
Bacteria have evolved a variety of defence mechanisms to protect against mobile genetic elements, including restriction-modification systems and CRISPR-Cas. In recent years, dozens of previously unknown defence systems (DSs) have been discovered. Notably, diverse DSs often coexist within the same genome, and some co-occur at frequencies significantly higher than would be expected by chance, implying potential synergistic interactions. Recent studies have provided evidence of defence mechanisms that enhance or complement one another. Here, we review the interactions between DSs at the mechanistic, regulatory, ecological and evolutionary levels.
Assuntos
Bacteriófagos , Sistemas CRISPR-Cas , Bactérias/genética , Evolução Biológica , Bacteriófagos/genéticaRESUMO
Background: Shigella is a major cause of diarrhea in young children worldwide. Multiple vaccines targeting Shigella are in development, and phase 3 clinical trials are imminent to determine efficacy against shigellosis. Methods: The Enterics for Global Health (EFGH) Shigella surveillance study is designed to determine the incidence of medically attended shigellosis in 6- to 35-month-old children in 7 resource-limited settings. Here, we describe the microbiological methods used to isolate and identify Shigella. We developed a standardized laboratory protocol for isolation and identification of Shigella by culture. This protocol was implemented across all 7 sites, ensuring consistency and comparability of results. Secondary objectives of the study are to determine the antibiotic resistance profiles of Shigella, compare isolation of Shigella from rectal swabs versus whole stool, and compare isolation of Shigella following transport of rectal swabs in Cary-Blair versus a modified buffered glycerol saline transport medium. Conclusions: Data generated from EFGH using culture methods described herein can potentially be used for microbiological endpoints in future phase 3 clinical trials to evaluate vaccines against shigellosis and for other clinical and public health studies focused on these organisms.
RESUMO
Whole-genome sequencing (WGS) has unparalleled ability to distinguish between bacteria, with many public health applications. The generation and analysis of WGS data require significant financial investment. We describe a systematic review summarizing economic analyses of genomic surveillance of bacterial pathogens, reviewing the evidence for economic viability. The protocol was registered on PROSPERO (CRD42021289030). Six databases were searched on 8 November 2021 using terms related to 'WGS', 'population surveillance' and 'economic analysis'. Quality was assessed with the Drummond-Jefferson checklist. Following data extraction, a narrative synthesis approach was taken. Six hundred and eighty-one articles were identified, of which 49 proceeded to full-text screening, with 9 selected for inclusion. All had been published since 2019. Heterogeneity was high. Five studies assessed WGS for hospital surveillance and four analysed foodborne pathogens. Four were cost-benefit analyses, one was a cost-utility analysis, one was a cost-effectiveness analysis, one was a combined cost-effectiveness and cost-utility analysis, one combined cost-effectiveness and cost-benefit analyses and one was a partial analysis. All studies supported the use of WGS as a surveillance tool on economic grounds. The available evidence supports the use of WGS for pathogen surveillance but is limited by marked heterogeneity. Further work should include analysis relevant to low- and middle-income countries and should use real-world effectiveness data.
Assuntos
Bactérias , Análise de Custo-Efetividade , Análise Custo-Benefício , Sequenciamento Completo do Genoma , Bactérias/genética , GenômicaRESUMO
BACKGROUND: Shigellosis, also known as bacillary dysentery, is caused by Shigella spp that spread through fecal-oral contact and was traditionally associated with international travel in England. However, sexual transmission of Shigella flexneri and Shigella sonnei among gay, bisexual, and other men who have sex with men (MSM) is now common. In September, 2021, emergence of extensively drug-resistant (XDR) S sonnei harbouring plasmid-encoded blaCTX-M-27 raised concerns over further spread of this extended-spectrum ß-lactamase-producing gene. Using national surveillance in England, we identified and characterised isolates of S flexneri harbouring blaCTX-M-27. METHODS: In this epidemiological study, we identified and phylogenetically characterised S flexneri isolates harbouring blaCTX-M-27 that were referred to the Gastrointestinal Bacterial Reference Unit (GBRU) at the UK Health Security Agency. All isolates referred to the GBRU undergo whole-genome sequencing, enabling antimicrobial resistance determination using genetic markers. Cases were defined as individuals diagnosed with S flexneri harbouring blaCTX-M-27 in England, with a specimen date between Sept 1, 2015, and June 12, 2022, who were phylogenetically confirmed as part of two t10 (approximately ten single nucleotide polymorphisms) clusters. Long-read sequencing elucidated the genomic location of blaCTX-M-27. Laboratory data, integrated with available demographic and clinical information from patient questionnaires, were summarised using descriptive statistics. FINDINGS: A sustained increase in cases of S flexneri harbouring blaCTX-M-27 (n=26) occurred from September, 2021, having been sporadically reported (n=11) in the preceding 6 years. blaCTX-M-27 acquisition events within S flexneri 2a established an XDR paraphyletic (n=8) cluster and a multidrug-resistant monophyletic (n=18) cluster. Cases were among adult male individuals (median age 37 years [IQR 31-46]) and, of the 13 individuals who completed a patient questionnaire, ten (77%) identified as MSM. Antimicrobial treatment was received by seven (54%) of 13 individuals, and four (31%) individuals were admitted to hospital. The IncFII plasmids harbouring blaCTX-M-27 showed high similarity to the XDR S sonnei outbreak plasmid, with 82% and 99% nucleotide similarity between the cluster plasmids and the XDR S sonnei outbreak plasmid. INTERPRETATION: We report emergence of XDR and multidrug-resistant S flexneri 2a harbouring blaCTX-M-27 among MSM in England. Epidemiological and plasmid similarities with the XDR S sonnei outbreak support horizontal acquisition events, emphasising the importance of mobilisable antimicrobial resistance and the need for genomic-based surveillance. FUNDING: National Institute for Health and Care Research Health Protection Research Unit in Gastrointestinal Infections at the University of Liverpool in partnership with the UK Health Security Agency.