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Comparative Genomic Reveals Clonal Heterogeneity in Persistent Staphylococcus aureus Infection

Persistent infections caused by Staphylococcus aureus remain a clinical challenge. Adaptational mechanisms of the pathogen influencing infection persistence, treatment success, and clinical outcome in these types of infections by S. aureus have not been fully elucidated so far. We applied a whole-ge...

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Autores principales: Klein, Sabrina, Morath, Benedict, Weitz, Daniel, Schweizer, Patrick A., Sähr, Aline, Heeg, Klaus, Boutin, Sébastien, Nurjadi, Dennis
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8900520/
https://www.ncbi.nlm.nih.gov/pubmed/35265532
http://dx.doi.org/10.3389/fcimb.2022.817841
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author Klein, Sabrina
Morath, Benedict
Weitz, Daniel
Schweizer, Patrick A.
Sähr, Aline
Heeg, Klaus
Boutin, Sébastien
Nurjadi, Dennis
author_facet Klein, Sabrina
Morath, Benedict
Weitz, Daniel
Schweizer, Patrick A.
Sähr, Aline
Heeg, Klaus
Boutin, Sébastien
Nurjadi, Dennis
author_sort Klein, Sabrina
collection PubMed
description Persistent infections caused by Staphylococcus aureus remain a clinical challenge. Adaptational mechanisms of the pathogen influencing infection persistence, treatment success, and clinical outcome in these types of infections by S. aureus have not been fully elucidated so far. We applied a whole-genome sequencing approach on fifteen isolates retrieved from a persistent S. aureus infection to determine their genetic relatedness, virulome, and resistome. The analysis of the genomic data indicates that all isolates shared a common clonal origin but displayed a heterogenous composition of virulence factors and antimicrobial resistance. This heterogeneity was reflected by different mutations in the rpoB gene that were related to the phenotypic antimicrobial resistance towards rifampicin and different minimal inhibitory concentrations of oxacillin. In addition, one group of isolates had acquired the genes encoding for staphylokinase (sak) and staphylococcal complement inhibitor (scn), leading to the truncation of the hemolysin b (hlb) gene. These features are characteristic for temperate phages of S. aureus that carry genes of the immune evasion cluster and confer triple conversion by integration into the hlb gene. Modulation of immune evasion mechanisms was demonstrated by significant differences in biofilm formation capacity, while invasion and intracellular survival in neutrophils were not uniformly altered by the presence of the immune evasion cluster. Virulence factors carried by temperate phages of S. aureus may contribute to the course of infection at different stages and affect immune evasion and pathogen persistence. In conclusion, the application of comparative genomic demonstrated clonal heterogeneity in persistent S. aureus infection.
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spelling pubmed-89005202022-03-08 Comparative Genomic Reveals Clonal Heterogeneity in Persistent Staphylococcus aureus Infection Klein, Sabrina Morath, Benedict Weitz, Daniel Schweizer, Patrick A. Sähr, Aline Heeg, Klaus Boutin, Sébastien Nurjadi, Dennis Front Cell Infect Microbiol Cellular and Infection Microbiology Persistent infections caused by Staphylococcus aureus remain a clinical challenge. Adaptational mechanisms of the pathogen influencing infection persistence, treatment success, and clinical outcome in these types of infections by S. aureus have not been fully elucidated so far. We applied a whole-genome sequencing approach on fifteen isolates retrieved from a persistent S. aureus infection to determine their genetic relatedness, virulome, and resistome. The analysis of the genomic data indicates that all isolates shared a common clonal origin but displayed a heterogenous composition of virulence factors and antimicrobial resistance. This heterogeneity was reflected by different mutations in the rpoB gene that were related to the phenotypic antimicrobial resistance towards rifampicin and different minimal inhibitory concentrations of oxacillin. In addition, one group of isolates had acquired the genes encoding for staphylokinase (sak) and staphylococcal complement inhibitor (scn), leading to the truncation of the hemolysin b (hlb) gene. These features are characteristic for temperate phages of S. aureus that carry genes of the immune evasion cluster and confer triple conversion by integration into the hlb gene. Modulation of immune evasion mechanisms was demonstrated by significant differences in biofilm formation capacity, while invasion and intracellular survival in neutrophils were not uniformly altered by the presence of the immune evasion cluster. Virulence factors carried by temperate phages of S. aureus may contribute to the course of infection at different stages and affect immune evasion and pathogen persistence. In conclusion, the application of comparative genomic demonstrated clonal heterogeneity in persistent S. aureus infection. Frontiers Media S.A. 2022-02-21 /pmc/articles/PMC8900520/ /pubmed/35265532 http://dx.doi.org/10.3389/fcimb.2022.817841 Text en Copyright © 2022 Klein, Morath, Weitz, Schweizer, Sähr, Heeg, Boutin and Nurjadi https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular and Infection Microbiology
Klein, Sabrina
Morath, Benedict
Weitz, Daniel
Schweizer, Patrick A.
Sähr, Aline
Heeg, Klaus
Boutin, Sébastien
Nurjadi, Dennis
Comparative Genomic Reveals Clonal Heterogeneity in Persistent Staphylococcus aureus Infection
title Comparative Genomic Reveals Clonal Heterogeneity in Persistent Staphylococcus aureus Infection
title_full Comparative Genomic Reveals Clonal Heterogeneity in Persistent Staphylococcus aureus Infection
title_fullStr Comparative Genomic Reveals Clonal Heterogeneity in Persistent Staphylococcus aureus Infection
title_full_unstemmed Comparative Genomic Reveals Clonal Heterogeneity in Persistent Staphylococcus aureus Infection
title_short Comparative Genomic Reveals Clonal Heterogeneity in Persistent Staphylococcus aureus Infection
title_sort comparative genomic reveals clonal heterogeneity in persistent staphylococcus aureus infection
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8900520/
https://www.ncbi.nlm.nih.gov/pubmed/35265532
http://dx.doi.org/10.3389/fcimb.2022.817841
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