Multidrug-resistant atypical variants of Shigella flexneri in China.
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ABSTRACT:
SUBMITTER: Qiu S
PROVIDER: S-EPMC3713959 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Investigation of the origins of multidrug resistant Shigella flexneri in a patient
| PRJEB39384 | ENA
Project description:Shigella flexneri is the major cause of shigellosis in developing countries. A new S. flexneri serotype, Xv, appeared in 2000 and replaced serotype 2a as the most prevalent serotype in China. Serotype Xv is a variant of serotype X, with phosphoethanolamine modification of its O antigen mediated by a plasmid that contained the opt gene. Serotype Xv isolates belong to sequence type 91 (ST91). In this study, whole-genome sequencing of 59 S. flexneri isolates of 14 serotypes (serotypes 1 to 4, Y, Yv, X, and Xv) indicated that ST91 arose around 1993 by acquiring multidrug resistance (MDR) and spread across China within a decade. A comparative analysis of the chromosome and opt-carrying plasmid pSFXv_2 revealed independent origins of 3 serotype Xv clusters in China, with different divergence times. Using 18 cluster-dividing single-nucleotide polymorphisms (SNPs), SNP typing divided 380 isolates from 3 provinces (Henan, Gansu, and Anhui) into 5 SNP genotypes (SGs). One SG predominated in each province, but substantial interregional spread of SGs was also evident. These findings suggest that MDR is the key selective pressure for the emergence of the S. flexneri epidemic clone and that Shigella epidemics in China were caused by a combination of local expansion and interregional spread of serotype Xv.
| S-EPMC3993495 | 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: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:To conduct the first comprehensive analysis of Shigella flexneri serotype 4s, a novel serotype found in 2010, we identified 24 serotype 4s isolates from 1973 shigellosis cases in China (2002-2014). The isolates were characterized by single nucleotide polymorphism (SNP) phylogenetic analysis, pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) to determine their genetic relatedness, and analysed further for their antimicrobial susceptibilities and antimicrobial resistance determinants. The PFGE and SNP phylogenetic analyses suggest that S. flexneri serotype 4s strains are derived from multiple serotypes, including two predominant serotypes in China: serotype X variant and serotype II. Three new sequence types were identified by MLST. All isolates were resistant to ticarcillin, ampicillin and tetracycline, with high-level resistance to third-generation cephalosporins. Notably, all the isolates were multidrug resistant (MDR), with the highest levels of resistance observed for eight antimicrobials classes. Most isolates contain various antimicrobial resistance determinants. In conclusion, we found that serotype 4s isolates have multiple evolutionary sources, diverse biochemical characteristics and genomes, and highly prevalent multidrug resistance and antimicrobial-resistant determinants. With few clinical treatment options, continuous monitoring and timely intervention against this emerging MDR serotype is essential. The possibility that serotype 4s will become the next predominant serotype exists.
| S-EPMC4931504 | biostudies-literature
Project description:An atypical Shigella flexneri strain with a plural agglutination pattern [i.e., reacting not only with serum samples containing type antigen II but also with serum samples containing group antigens (3)4 and 7(8)] was selected for genome sequencing, with the aim of obtaining additional comparative information about such strains.The genomic DNA of atypical S. flexneri strain NCCP 15744 was sequenced using an Ion Torrent PGM sequencing machine (Life Technologies, USA). The raw sequence data were preprocessed and reference-assembled in the CLC Assembly Cell software (version 4.0.6; CLC bio, USA).Ion Torrent sequencing produced 1,450,025 single reads with an average length of 144 bp, totaling ~209 Mbp. The NCCP 15744 genome is composed of one chromosome and four plasmids and contains a gtrX gene. Among the published genome sequences of S. flexneri strains, including 2457T, Sf301, and 2002017, strain NCCP 15744 showed high similarity with strain 2002017. The differences between NCCP 15744 and 2002017 are as follows: i) NCCP 15744 carries four plasmids whereas 2002017 carries five; ii) 19 genes (including CI, CII, and cro) were lost in the SHI-O genomic island of NCCP 15744 and six genes were gained as compared with strain 2002017.Strain NCCP 15744 is genetically similar to 2002017, but these two strains have different multilocus sequence types and serotypes. The exact reason is unclear, but the 19 lost genes may be responsible for the atypical seroconversion of strain NCCP 15744.
| S-EPMC5402852 | biostudies-other
Project description:Shigella flexneri has been a major public health problem in developing countries. This work analyzed the frequency of 16 virulence genes, the genotypic diversity, and the antimicrobial resistance profiles of 130 S. flexneri strains isolated in Brazil. The ipaH gene was found in all the 130 strains. The frequencies of the other genes were variable ial (88.5%), sigA (82.3%), iuc (74.6%), virA (73%), pic (72.3%), virF (57.7%), sat (48.5%), ipaBCD (37%), sen (36%), set1A (35.4%), sepA (30%), set1B (30%), virB (14%), icsA (10%), and ipgD (5.4%). A total of 57 (43.8%) strains were multidrug-resistant. ERIC-PCR grouped 96 of the strains into a single cluster with ≥ 70.4% of similarity, 75 of these strains presented a similarity ≥ 80.9%. PFGE grouped 120 of the strains into a single cluster with 57.4% of similarity and 82 of these strains presented a similarity ≥ 70.6%. In conclusion, the high frequency of some virulence genes reinforces the pathogenic potential of the strains studied. The high rates of MDR strains are alarming once it may lead to failure when antimicrobial treatment is necessary. Genotype techniques reveled a major cluster with high genetic similarity including S. flexneri strains from the different Brazilian states and distinct years of isolation, showing that they probably emerged from a common ancestor.
| S-EPMC7688809 | 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:Since the initial discovery of mcr-1 in an Escherichia coli isolate from China, the gene has also been detected in Klebsiella pneumoniae and Salmonella enterica but is rarely reported in other Enterobacteriaceae Here, we report the isolation and identification of a Shigella flexneri strain harboring mcr-1 from stool samples in a pig farm in China from 2009. The MIC of colistin for the isolate is 4 μg/ml. Conjugation assays showed that the donor S. flexneri strain has functional and transferable colistin resistance. Sequencing revealed that mcr-1 was present on a putative composite transposon flanked by inverted repeats of ISApl1IMPORTANCE There are four species of Shigella, and Shigella flexneri is the most frequently isolated species in low- and middle-income countries (LMICs). In this study, we report a functional, transferable, plasmid-mediated mcr-1 gene in S. flexneri We have shown that mcr-1 is located on a novel composite transposon which is flanked by inverted repeats of ISApl1 The host strain is multidrug resistant, and this multidrug resistance is also transferable. The finding of a functional mcr-1 gene in S. flexneri, a human-associated Enterobacteriaceae family member, is a cause for concern as infections due to S. flexneri are the main Shigella infections in most low- and middle-income countries.
| S-EPMC5881045 | biostudies-literature
Project description:Shigella flexneri serotype 2 variant (II:3,4,7,8) was isolated in 2008 and first reported in China in 2013. In the present study, epidemiological surveillance from 2003 to 2013 in China suggested that this serotype first appeared in Guangxi in 2003; it then emerged in Shanghai and Xinjiang in 2004 and in Henan in 2008. Of the 1813 S. flexneri isolates, 58 S. flexneri serotype 2 variant strains were identified. Serotype 2 variant has emerged as a prominent serotype in recent years, with 2a (32.6%), X variant (25.2%), 1a (9.4%), X (6.3%), 2b (5.4%), and 1b (3.6%). According to phenotypic and genotypic analysis, the serotype 2 variant originated from 2a to 2b. A higher antibiotic resistance rate was observed between 2009 and 2013 than that between 2003 and 2008. Among 22 cephalosporin-resistant isolates, bla TEM-1, bla OXA-1, bla CTX-3, bla CTX-14, and bla CTX-79 were detected. Among 22 fluoroquinolone-resistant isolates, a Ser80Ile mutation in parC was present in all of the isolates. Moreover, 21 isolates had three gyrA point mutations (Ser83Leu, His211Tyr, Asp87Asn, or Gly) and one isolate had two gyrA point mutations (Ser83Leu and His211Tyr). The prevalence of His211Tyr in the fluoroquinolone-resistant isolates is concerning, and the mutation was first reported in China. Besides, 22 isolates harbored the aac(6')-Ib-cr gene, and two isolates harbored qnrS1. In view of the increased epidemic frequency and multidrug-resistant strain emergence, continuous surveillance will be needed to understand the actual disease burden and provide guidance for shigellosis.
| S-EPMC4423435 | biostudies-literature