Reduced In Vitro Susceptibility of Streptococcus pyogenes to β-Lactam Antibiotics Associated with Mutations in the pbp2x Gene Is Geographically Widespread.

Autor:	Musser JM; Center for Molecular and Translational Human Infectious Diseases Research, Houston Methodist Research Institute and Houston Methodist Hospital, Houston, Texas, USA jmmusser@houstonmethodist.org.; Clinical Microbiology Laboratory, Department of Pathology and Genomic Medicine, Houston Methodist Research Institute and Houston Methodist Hospital, Houston, Texas, USA.; Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, New York, USA., Beres SB; Center for Molecular and Translational Human Infectious Diseases Research, Houston Methodist Research Institute and Houston Methodist Hospital, Houston, Texas, USA.; Clinical Microbiology Laboratory, Department of Pathology and Genomic Medicine, Houston Methodist Research Institute and Houston Methodist Hospital, Houston, Texas, USA., Zhu L; Center for Molecular and Translational Human Infectious Diseases Research, Houston Methodist Research Institute and Houston Methodist Hospital, Houston, Texas, USA.; Clinical Microbiology Laboratory, Department of Pathology and Genomic Medicine, Houston Methodist Research Institute and Houston Methodist Hospital, Houston, Texas, USA., Olsen RJ; Center for Molecular and Translational Human Infectious Diseases Research, Houston Methodist Research Institute and Houston Methodist Hospital, Houston, Texas, USA.; Clinical Microbiology Laboratory, Department of Pathology and Genomic Medicine, Houston Methodist Research Institute and Houston Methodist Hospital, Houston, Texas, USA.; Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, New York, USA., Vuopio J; Institute of Biomedicine, University of Turku, Turku, Finland.; Turku University Hospital, Department of Clinical Microbiology, Turku, Finland., Hyyryläinen HL; Department of Health Security, Finnish Institute for Health and Welfare, Helsinki, Finland., Gröndahl-Yli-Hannuksela K; Institute of Biomedicine, University of Turku, Turku, Finland., Kristinsson KG; Department of Clinical Microbiology, Landspitali University Hospital, Reykjavik, Iceland.; Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland., Darenberg J; Public Health Agency of Sweden, Solna, Sweden., Henriques-Normark B; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.; Department of Laboratory Medicine, Division of Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden., Hoffmann S; Neisseria and Streptococcus Reference Laboratory, Bacteria, Parasites & Fungi, Infectious Disease Preparedness, Statens Serum Institut, Copenhagen, Denmark., Caugant DA; Division for Infection Control and Environmental Health, Norwegian Institute of Public Health, Oslo, Norway., Smith AJ; College of Medical, Veterinary and Life Sciences, Glasgow Dental Hospital and School, University of Glasgow, Glasgow, Scotland.; Scottish Microbiology Reference Laboratory, Glasgow, Scotland., Lindsay DSJ; Scottish Microbiology Reference Laboratory, Glasgow, Scotland., Boragine DM; Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas, USA., Palzkill T; Department of Pharmacology and Chemical Biology, Baylor College of Medicine, Houston, Texas, USA.
Jazyk:	angličtina
Zdroj:	Journal of clinical microbiology [J Clin Microbiol] 2020 Mar 25; Vol. 58 (4). Date of Electronic Publication: 2020 Mar 25 (Print Publication: 2020).
DOI:	10.1128/JCM.01993-19
Abstrakt:	Recently, two related Streptococcus pyogenes strains with reduced susceptibility to ampicillin, amoxicillin, and cefotaxime, antibiotics commonly used to treat S. pyogenes infections, were reported. The two strains had the same nonsynonymous (amino acid-substituting) mutation in the pbp2x gene, encoding penicillin-binding protein 2X (PBP2X). This concerning report led us to investigate our library of 7,025 genome sequences of type emm1 , emm28 , and emm89 S. pyogenes clinical strains recovered from intercontinental sources for mutations in pbp2x We identified 137 strains that, combined, had 37 nonsynonymous mutations in 36 codons in pbp2x Although to a lesser magnitude than the two previously published isolates, many of our strains had decreased susceptibility in vitro to multiple beta-lactam antibiotics. Many pbp2x mutations were found only in single strains, but 16 groups of two or more isolates of the same emm type had an identical amino acid replacement. Phylogenetic analysis showed that, with one exception, strains of the same emm type with the same amino acid replacement were clonally related by descent. This finding indicates that strains with some amino acid changes in PBP2X can successfully spread to new human hosts and cause invasive infections. Mapping of the amino acid changes onto a three-dimensional structure of the related Streptococcus pneumoniae PBP2X suggests that some substitutions are located in regions functionally important in related pathogenic bacterial species. Decreased beta-lactam susceptibility is geographically widespread in strains of numerically common emm gene subtypes. Enhanced surveillance and further epidemiological and molecular genetic study of this potential emergent antimicrobial problem are warranted. (Copyright © 2020 American Society for Microbiology.)
Databáze:	MEDLINE
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