Dataset Information

Genetic Mechanisms behind the Spread of Reduced Susceptibility to Azithromycin in Shigella Strains Isolated from Men Who Have Sex with Men in Quebec, Canada.

ABSTRACT: We analyzed 254 Shigella species isolates collected in Québec, Canada, during 2013 and 2014. Overall, 23.6% of isolates showed reduced susceptibility to azithromycin (RSA) encoded by mphA (11.6%), ermB (1.7%), or both genes (86.7%). Shigella strains with RSA were mostly isolated from men who have sex with men (68.8% or higher) from the Montreal region. A complete sequence analysis of six selected plasmids from Shigella sonnei and different serotypes of Shigella flexneri emphasized the role of IS26 in the dissemination of RSA.

SUBMITTER: Yousfi K

PROVIDER: S-EPMC6355565 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Genetic Mechanisms behind the Spread of Reduced Susceptibility to Azithromycin in Shigella Strains Isolated from Men Who Have Sex with Men in Québec, Canada.

Yousfi Khadidja K Gaudreau Christiane C Pilon Pierre A PA Lefebvre Brigitte B Walker Matthew M Fournier Éric É Doualla Bell Florence F Martineau Christine C Longtin Jean J Bekal Sadjia S

Antimicrobial agents and chemotherapy 20190129 2

We analyzed 254 Shigella species isolates collected in Québec, Canada, during 2013 and 2014. Overall, 23.6% of isolates showed reduced susceptibility to azithromycin (RSA) encoded by mphA (11.6%), ermB (1.7%), or both genes (86.7%). Shigella strains with RSA were mostly isolated from men who have sex with men (68.8% or higher) from the Montreal region. A complete sequence analysis of six selected plasmids from Shigella sonnei and different serotypes of Shige ...[more]

PMID: 30455248

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Project description:Multidrug-resistant (MDR) Shigella sonnei have become prevalent among men who have sex with men and have become a global public health concern. From June 2017 to April 2019, 32 men were infected with MDR S. sonnei acquired locally, in Montréal, which was suggestive of an outbreak. Antimicrobial susceptibility testing, whole-genome sequencing (WGS), phylogenetic analysis, antimicrobial resistance and virulence characterization, and association to international clusters were performed. The outbreak strain was ceftriaxone- and azithromycin-resistant due to the acquisition of blaCTX-M-27, and mphA and ermB genes, respectively, with reduced susceptibility to ciprofloxacin due to a single point mutation (gyrA S83L). One out of 27 patients treated with a fluoroquinolone experienced microbiological failure. Epidemiological evidence first supported by a rare unique MDR Shigella sonnei documented only in men in 2017 followed by similar pulsed-field gel electrophoresis profiles was confirmed by WGS. A core genome high-quality single-nucleotide variant (hqSNV)-based phylogeny found a median of 6 hqSNV differences among isolates. Virulence gene content was investigated, but no Shiga toxins were detected. An international cluster of highly related isolates was identified (PDS000019750.208) and belonged to the 3.7.29.1.4.1 S. sonnei genotype (Global III VN2.KH1.Aus). Genomic analysis revealed that this Montréal cluster was connected to other documented outbreaks in Australia, the United States, and the United Kingdom. This study highlights the urgent need for public health measures to focus on the prevention and the early detection of S. sonnei, since global transmission patterns of MDR strains is concerning and few antimicrobial treatment options are available. IMPORTANCE Shigella sonnei, an important foodborne pathogen, recently became a frequent sexually transmitted agent involved in large and persistent outbreaks globally among men who have sex with men. Most strains also harbor several multidrug-resistant (MDR) determinants of particular concern. This study characterizes an outbreak strain at the source of an important MDR cluster identified in Montréal in 2017. Associations were made to many high-profile international outbreaks, and the causative S. sonnei lineage of these clusters was identified, which was not evident in past reports. The worldwide occurrence of this strain is of concern since treatment with antimicrobials like ceftriaxone and azithromycin may not be effective, and rare microbiological failures have been documented in patients treated with ciprofloxacin. Our investigation highlights the threats of Shigella spp. infection and the necessity for antimicrobial susceptibility monitoring in order to mitigate S. sonnei's impact on public health and to avoid transmission to other at-risk communities.

Project description:Objective:The aims of this study were to describe azithromycin (AZM) susceptibility patterns among Shigella isolates in Anhui, China and identify predictors of resistance with mobile element-mediated genes. Methods:A total of 517 non-duplicate Shigella isolates (449 S. flexneri and 68 S. sonnei) were collected in the Anhui Province of China from September 2011-September 2015, and screened for the plasmid-mediated genes of decreased susceptibility to AZM (DSA), using polymerase chain reaction amplification and sequencing. Conjugation experiments and pulsed-field gel electrophoresis were conducted for all mphA-positive DSA isolates. Results:The DSA rate for 449 S. flexneri isolates was 33.6%, compared with 39.7% for 68 S. sonnei isolates. Among 161 DSA S. flexneri isolates, 93 (57.8%) carried the mphA gene. Among 27 DSA S. sonnei isolates, 11 (40.7%) carried the mphA gene. However, other plasmid-mediated DSA genes were not found in these isolates. A total of 89 transconjugants (95.7%) were obtained from 93 mphA-positive S. flexneri isolates through conjugation, and 10 transconjugants (90.9%) were obtained from 11 mphA-positive S. sonnei isolates. Furthermore, the minimum inhibitory concentrations (MICs) of AZM among 89 S. flexneri transconjugants ranged from 4 to 128 ?g/mL, with an MIC50 of 8 ?g/mL and MIC90 of 32 ?g/mL. The MICs of AZM among 10 S. sonnei transconjugants ranged from 4 to 256 ?g/mL, with an MIC50 of 8 ?g/mL and MIC90 of 64 ?g/mL. Thirteen clusters were found for mphA-positive S. flexneri, and five clusters were found for mphA-positive S. sonnei. Furthermore, 10 homologous isolates among 13 mphA-positive S. flexneri isolates with high-level DSA were from Sixian county and were multidrug-resistant strains. Of the 10 homologous S. flexneri isolates, eight were from children (?5 years old), and two from the elderly (>60 years old). Conclusion:Our study demonstrates that the DSA for Shigella isolates was severe, and the plasmid-mediated mphA gene was the most common macrolide resistance gene detected in Shigella isolates collected in Anhui, China. The mphA-positive S. flexneri isolates with high-level DSA facilitated clonal spread in children and the elderly. This finding is noteworthy and warrants further study.

Dataset Information

Genetic Mechanisms behind the Spread of Reduced Susceptibility to Azithromycin in Shigella Strains Isolated from Men Who Have Sex with Men in Quebec, Canada.

Publications

Genetic Mechanisms behind the Spread of Reduced Susceptibility to Azithromycin in <i>Shigella</i> Strains Isolated from Men Who Have Sex with Men in Québec, Canada.

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