Unexpected relationships between frequency of antimicrobial resistance, disease phenotype and emm type in group A Streptococcus

Abstract

Despite universal susceptibility to β-lactams, resistance to second-line antimicrobials (e.g. erythromycin) is increasingly common among group A Streptococcus (GAS). To better understand the frequency of regional GAS antimicrobial resistance, we screened a previously described GAS strain collection from Houston, TX, USA, for resistance to commonly used antimicrobials. A total of 100/929 (10.8 %) showed resistance to at least one antimicrobial. Tetracycline resistance was identified in 52 (5.6 %) GAS strains. The cumulative frequency of erythromycin and clindamycin resistance [macrolide (M) and macrolide-lincosamide-streptogramin (MLS) phenotypes] was greatest among invasive GAS strains (9.9 %) compared to that of strains derived from any other infection type (5.9 %, P=0.045). We identified emm types 11, 75, 77 and 92 as the only emm types with high (e.g. >50 %) within-emm type resistance and contributing to the majority (24/26; 92 %) of erythromycin/clindamycin resistance in invasive GAS. High-frequency resistance emm types were also significantly overrepresented in invasive GAS strains as indicated by invasive index. We performed whole-genome sequencing to define genetic elements associated with resistance among emm types 11, 75, 77 and 92. Diverse mobile elements contributed to GAS resistance including transposons, integrative conjugative elements, prophage and a plasmid. Phylogenetic analysis suggests recent clonal emergence of emm92 GAS strains. Our findings indicate that less frequently encountered GAS emm types disproportionately contribute to resistance phenotypes, are defined by diverse mobile genetic elements and may favour invasive disease.

Plasma Protein Layer Concealment Protects Streptococcus pyogenes From Innate Immune Attack

“…However, in cases of allergic reactions towards penicillin, antibiotics such as tetracycline, macrolides, and lincosamides are used as replacement therapy. While streptococcal resistances towards penicillin do not constitute a clinical problem, resistances to tetracycline and the other mentioned antibiotics have started to emerge ( Sanson et al., 2019 ). Considering this aspect, we decided to focus on tetracycline throughout the remaining part of this study.…”

“…Streptococcus pyogenes is a Gram-positive, nearly-exclusively human pathogen causing an estimated 600 million infections per year ( Carapetis et al., 2005 ) of which more than 18 million are serious ( Ralph and Carapetis, 2013 ). Notably, evidence is emerging that S. pyogenes can develop resistances to antibiotics such as tetracycline ( Sanson et al., 2019 ), β-lactam antibiotics ( Yu et al., 2020 ), and macrolides ( Sanson et al., 2019 ). Considering that S. pyogenes is found in the list of the top ten causes of mortality from infectious diseases ( Ralph and Carapetis, 2013 ), the occurrence of antibiotic resistances bears the risk of a worldwide increase of severe streptococcal infections.…”

Reducing Broad-Spectrum Antibiotic Treatment of Simple Group A Streptococcal Infections to Reduce Harm to the Microbiome

“…While GAS is 100% sensitive to penicillins and cephalosporins, there is growing resistance to macrolides (azithromycin) and clindamycin. Additionally, GAS sometimes possesses inducible macrolide-lincosamide-streptogramin (MLS) resistance [ 15 ].…”

Population Genomics of emm4 Group A Streptococcus Reveals Progressive Replacement with a Hypervirulent Clone in North America

“…For all short-read, Illumina-based sequencing, high-quality genomic DNA was extracted from GAS cells grown overnight at 37°C and 5% CO 2 on SBA using the Qiagen DNeasy kit modified for Gram-positive bacteria as previously described ( 63 ). Genomic DNA used in Oxford Nanopore long-read sequencing was extracted from cells using a cetyl trimethylammonium bromide (CTAB) protocol adapted for GAS to enrich for longer DNA fragments.…”

“…Raw Illumina-based platform sequencing reads were processed for de novo assembly and polymorphism discovery as previously described ( 63 ). Briefly, raw reads (150-bp paired end [PE] for HiSeq4000 or 300-bp PE for MiSeq) underwent error correction and de novo assembly using SPAdes (v3.12.0) ( 64 ).…”