Dataset Information

Invasive Multidrug-Resistant emm93.0 Streptococcus pyogenes Strain Harboring a Novel Genomic Island, Israel, 2017-2019.

ABSTRACT: Invasive group A Streptococcus (iGAS) infections have increased in Israel since 2016 as successful lineages have emerged. We report the emergence and outbreak of a multidrug-resistant S. pyogenes emm93.0, sequence type 10, among iGAS infections in Israel since 2017. This type has been observed very rarely in other countries. During this period, emm93.0 was the cause of 116 infections in Israel and became the leading type during 2018. Most of the infections were from bacteremia (75%), and most patients were male (76%). We observed infections across Israel, mainly in adults. Of note, we observed multidrug resistance for clindamycin, tetracycline, and trimethoprim/sulfamethoxazole. Whole-genome sequencing confirmed clonality among geographically disseminated isolates. The local emm93.0 sequence type 10 clone contained a novel genomic island harboring the resistance genes lsa(E), lnu(B), and ant (6)-Ia aph(3')-III. Further phenotypic and genomic studies are required to determine the prevalence of this resistance element in other iGAS types.

SUBMITTER: Ron M

PROVIDER: S-EPMC8714194 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Invasive Multidrug-Resistant emm93.0 Streptococcus pyogenes Strain Harboring a Novel Genomic Island, Israel, 2017-2019.

Ron Merav M Brosh-Nissimov Tal T Korenman Zinaida Z Treygerman Orit O Sagi Orli O Valinsky Lea L Rokney Assaf A

Emerging infectious diseases 20220101 1

Invasive group A Streptococcus (iGAS) infections have increased in Israel since 2016 as successful lineages have emerged. We report the emergence and outbreak of a multidrug-resistant S. pyogenes emm93.0, sequence type 10, among iGAS infections in Israel since 2017. This type has been observed very rarely in other countries. During this period, emm93.0 was the cause of 116 infections in Israel and became the leading type during 2018. Most of the infections were from bacteremia (75%), and most pa ...[more]

PMID: 34932442

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Project description:BackgroundStreptococcus pyogenes is a major cause of severe, invasive infections in humans. The bacterial pathogen harbors a wide array of virulence factors and exhibits high genomic diversity. Rapid changes of circulating strains in a community are common. Understanding the current prevalence and dynamics of S. pyogenes lineages could inform vaccine development and disease control strategies.MethodsWe used whole-genome sequencing (WGS) to characterize all invasive S. pyogenes isolates obtained through the United States Center for Disease Control and Prevention's Active Bacterial Core surveillance (ABCs) in 2016 and 2017. We determined the distribution of strain features, including emm type, antibiotic resistance determinants, and selected virulence factors. Changes in strain feature distribution between years 2016 and 2017 were evaluated. Phylogenetic analysis was used to identify expanding lineages within emm type.ResultsSeventy-one emm types were identified from 3873 isolates characterized. The emm types targeted by a 30-valent M protein-based vaccine accounted for 3230 (89%) isolates. The relative frequencies of emm types collected during the 2 years were similar. While all isolates were penicillin-susceptible, erythromycin-resistant isolates increased from 273 (16% of 2016 isolates) to 432 (23% of 2017 isolates), mainly driven by increase of the erm-positive emm types 92 and 83. The prevalence of 24 virulence factors, including 11 streptococcal pyrogenic toxins, ranged from 6 to 90%. In each of three emm types (emm 49, 82, and 92), a subgroup of isolates significantly expanded between 2016 and 2017 compared to isolates outside of the subgroup (P-values < 0.0001). Specific genomic sequence changes were associated with these expanded lineages.ConclusionsWhile the overall population structure of invasive S. pyogenes isolates in the United States remained stable, some lineages, including several that were antibiotic-resistant, increased between 2016 and 2017. Continued genomic surveillance can help monitor and characterize bacterial features associated with emerging strains from invasive infections.

Project description:Streptococcus pyogenes chromosomal island M1 (SpyCIM1) integrates by site-specific recombination into the 5' end of DNA mismatch repair (MMR) gene mutL in strain SF370SmR, blocking transcription of it and the downstream operon genes. During exponential growth, SpyCIM1 excises from the chromosome and replicates as an episome, restoring mutL transcription. This process is reversed in stationary phase with SpyCIM1 re-integrating into mutL, returning the cells to a mutator phenotype. Here we show that elimination of SpyCIM1 relieves this mutator phenotype. The downstream MMR operon genes, multidrug efflux pump lmrP, Holliday junction resolution helicase ruvA, and DNA base excision repair glycosylase tag, are also restored to constitutive expression by elimination of SpyCIM1. The presence of SpyCIM1 alters global transcription patterns in SF370SmR. RNA sequencing (RNA-Seq) demonstrated that loss of SpyCIM1 in the SpyCIM1 deletion mutant, CEM1Δ4, impacted the expression of over 100 genes involved in virulence and metabolism both in early exponential phase, when the SpyCIM1 is episomal, as well as at the onset of stationary phase, when SpyCIM1 has reintegrated into mutL. Among these changes, the up-regulation of the genes for the antiphagocytic M protein (emm1), streptolysin O (slo), capsule operon (hasABC), and streptococcal pyrogenic exotoxin (speB), are particularly notable. The expression pattern of the MMR operon confirmed our earlier observations that these genes are transcribed in early exponential phase but silenced as stationary phase is approached. Thus, the direct role of SpyCIM1 in causing the mutator phenotype is confirmed, and further, its influence upon the biology of S. pyogenes was found to impact multiple genes in addition to the MMR operon, which is a novel function for a mobile genetic element. We suggest that such chromosomal islands are a remarkable evolutionary adaptation to promote the survival of its S. pyogenes host cell in changing environments.

Dataset Information

Invasive Multidrug-Resistant emm93.0 Streptococcus pyogenes Strain Harboring a Novel Genomic Island, Israel, 2017-2019.

Publications

Invasive Multidrug-Resistant emm93.0 Streptococcus pyogenes Strain Harboring a Novel Genomic Island, Israel, 2017-2019.

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