Virulence Determinants in Staphylococcus aureus Clones Causing Osteomyelitis in Italy.

Fernanda Pimentel De Araujo,Tiziana Cassetti,Monica Monaco,Maria Del Grosso,Annalisa Pantosti,Eleonora Riccobono,Raffaele Gargiulo,Simone Ambretti,Paolo Visca,Mattia Pirolo,Donatella Lombardo

doi:10.3389/fmicb.2022.846167

Abstract

Staphylococcus aureus is the most common pathogen causing osteomyelitis (OM). The aim of this study was to explore the clonal complex (CC) distribution and the pattern of virulence determinants of S. aureus isolates from OM in Italy. Whole-genome sequencing was performed on 83 S. aureus isolates from OM cases in six hospitals. Antibiotic susceptibility tests showed that 30.1% of the isolates were methicillin-resistant S. aureus (MRSA). The most frequent CCs detected were CC22, CC5, CC8, CC30, and CC15, which represent the most common lineages circulating in Italian hospitals. MRSA were limited in the number of lineages (CC22, CC5, CC8, and CC1). Phylogenetic analysis followed the sequence type-CC groupings and revealed a non-uniform distribution of the isolates from the different hospitals. No significant difference in the mean number of virulence genes carried by MRSA or MSSA isolates was observed. Some virulence genes, namely cna, fib, fnbA, coa, lukD, lukE, sak, and tst, were correlated with the CC. However, different categories of virulence factors, such as adhesins, exoenzymes, and toxins, were frequently detected and unevenly distributed among all lineages. Indeed, each lineage carried a variable combination of virulence genes, likely reflecting functional redundancy, and arguing for the importance of those traits for the pathogenicity in OM. In conclusion, no specific genetic trait in the most frequent lineages could explain their high prevalence among OM isolates. Our findings highlight that CCs detected in OM isolates follow the epidemiology of S. aureus infections in the country. It is conceivable that any of the most common S. aureus CC can cause a variety of infections, including OM.

Highlights

Osteomyelitis (OM) is an infective and inflammatory process of the bone, which can progress to osteonecrosis and bone destruction
The purpose of this study was to identify the pattern of virulence determinants and the clonal distribution of S. aureus isolates from OM in Italy, by using whole-genome sequencing (WGS) for a detailed genetic characterization
The phylogenetic relationship based on Core genome MLST (cgMLST) revealed a non-uniform distribution of the isolates that clustered together according to the Sequence Types (ST)-clonal complex (CC) grouping, regardless of the geographic origin or methicillin resistance status

Summary

Introduction

Osteomyelitis (OM) is an infective and inflammatory process of the bone, which can progress to osteonecrosis and bone destruction. Despite the improvement in the diagnosing of OM, the incidence of OM has been increasing over the last few decades. This could be ascribed to the increase of certain risk factors such as diabetes and surgery procedures such as arthroplasty (Kurtz et al, 2012; Geraghty and LaPorta, 2019). In the United States (US), the average orthopaedic surgical volume increased of 38% in the last 3 years (Shukla et al, 2021) and is estimated that by 2030, 572,000 hip revisions and 3.48 million knee revisions could be performed with an increase of 174 and 673%, respectively (Kurtz et al, 2012). In line with the increase of arthroplasty, the incidence of OM increased from 11.4 to 24.2 cases per 100,000 person-years in four decades in United States (Kremers et al, 2015). If a prosthetic-joint infection develops, revision surgery for removal of the implant is often required, which leads to prolonged hospitalization and a high risk of re-infection (Trampuz and Zimmerli, 2008)

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