Comparative Genomic Reveals Clonal Heterogeneity in Persistent Staphylococcus aureus Infection.

Sabrina Klein,Klaus Heeg,Patrick A Schweizer,Aline Sähr,Daniel Weitz,Dennis Nurjadi,Sébastien Boutin,Benedict Morath

doi:10.3389/fcimb.2022.817841

Abstract

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.

Highlights

Staphylococcus aureus is one of the most prevalent and clinically relevant pathogens and exerts a wide repertoire of virulence factors (Tong et al, 2015)
Fifteen S. aureus clinical isolates from a 74-year-old, male patient with multiple episodes of S. aureus Bloodstream infection (BSI) over a period of 11 months were analyzed in this study
Two groups of isolates were identified by the presence or absence of the virulence genes sak and scn, and the truncation of hlb

Summary

Introduction

Staphylococcus aureus is one of the most prevalent and clinically relevant pathogens and exerts a wide repertoire of virulence factors (Tong et al, 2015). Bloodstream infection (BSI) is one of the major manifestations and may, among other foci, be caused by infected foreign material. S. aureus infections associated with foreign bodies like prosthetic joints, heart valves, and implanted devices. Clonal Heterogeneity in S. aureus Infection often result in recurrent or persistent infections, posing a challenge to clinicians (Thwaites et al, 2011). The ability of S. aureus to cause recurrent or persistent infections has been attributed to several pathogenic mechanisms. Biofilm formation is a key component of S. aureus virulence in infections involving foreign bodies by establishing a protected niche where persistence even during antibiotic therapy may be facilitated (Moormeier and Bayles, 2017). It has been proposed that intracellular survival in leukocytes can lead to dissemination via the bloodstream (Thwaites and Gant, 2011; Mulcahy et al, 2020; Pidwill et al, 2020)

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