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Comparative Genomic Analyses Reveal Potential Factors Responsible for the ST6 Oxacillin-Resistant Staphylococcus lugdunensis Endemic in a Hospital.

ABSTRACT: Oxacillin-resistant Staphylococcus lugdunensis (ORSL) is considered a life-threatening isolate in healthcare settings. Among ORSL clones, ST6-SCCmec II strains are associated with an endemic spread in hospitals. We analyzed the complete genome of ORSL CGMH-SL118, a representative strain. Results revealed that this strain contained three MGEs (two prophages and one plasmid) other than the SCCmec II element, which showed remarkable differences in genome organization compared to the reference strains from NCBI. Eight multidrug-resistant genes were identified. All but blaZ were carried by MGEs, such as the SCCmec II element [mecA, ant (9)-Ia, and ermA] and the prophage φSPbeta [aac (6')-aph (2'), aph (3')-III, and ant (6)-Ia], indicating that MGEs carrying multidrug-resistant genes may be important for ST6 strains. The prophage φSPbeta contains sasX gene, which was responsible for the pathogenesis of Staphylococcus aureus. A phage-mediated resistant island containing fusB (SlRI fusB-118) was found near φSPbeta, which was highly homologous to type III SeRI fusB-5907 of Staphylococcus epidermidis. In contrast to previous studies, over 20% of ST6 isolates showed a fusidic acid-resistant phenotype, suggesting that phage-mediated intraspecies transmission of resistant islands may become an important issue for ST6 strains. Sixty-eight clinical isolates of ST6 Staphylococcus lugdunensis (50 OSSL, oxacillin-sensitive S. lugdunensis, and 18 ORSL, including CGMH-SL118) collected from various types of specimens in the hospital were studied. Among these isolates in this study, ORSL showed similar drug-resistant genes and phenotypes as CGMH-SL118. The comparative genomic analyses highlight the contribution of MGEs in the development and dissemination of antimicrobial resistance in ST6 strains, suggesting that resistance determinants and virulence factors encoded by MGEs provide a survival advantage for successful colonization and spread in healthcare settings.

SUBMITTER: Chang SC

PROVIDER: S-EPMC8655729 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Introduction.Staphylococcus aureus is a major cause of hospital infections worldwide. Awareness towards methicillin-resistant S. aureus (MRSA) infections is high but attention towards borderline oxacillin-resistant S. aureus (BORSA) is limited, possibly due to an underestimated clinical relevance, presumption of low incidence and diagnostic limitations.Gap statement. BORSA surveillance has not been routinely implemented, and thus consensus with regard to a definition and infection control measures is lacking.Aim. Our goals were to investigate the occurrence, molecular characteristics and clinical manifestations of BORSA infections in the hospital setting.Methodology. Following an increased incidence in 2016, BORSA cases in 2014/2016 (in our institution) were more specifically evaluated. Medical records were reviewed to investigate epidemiological links, clinical characteristics and outcomes. Resistance and virulence markers were assessed by whole genome sequencing (WGS). Conventional methods: amplified fragment length polymorphism (AFLP) ; multilocus sequence typing (MLST) and multiple locus variable-number tandem repeat analysis (MLVA) were compared with core genome MLST (cgMLST) and whole-genome single nucleotide polymorphism (wgSNP) analysis to confirm genetic clusters.Results. From 2009 to 2013, BORSA comprised 0.1 % of all clinical S. aureus strains. In 2016, the incidence was six-fold higher in comparison to the baseline. Whole-genome SNP and cgMLST confirmed two BORSA clusters among patients with dermatological conditions. Patients with BORSA presented with skin infections, and one case developed a severe invasive infection with a fatal outcome. Infection control measures successfully prevented further transmission in both clusters. WGS findings showed that BORSA strains carried multiple resistance and virulence genes with increased pathogenic potential.Conclusion. WGS and cgMLST effectively characterized and confirmed BORSA clusters among at-risk patients with clinical manifestations ranging from mild skin infections to life-threatening bacteraemia. Clinical awareness and active monitoring are therefore warranted for the timely implementation of infection control measures to prevent BORSA transmission in high-risk patients.

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Comparative Genomic Analyses Reveal Potential Factors Responsible for the ST6 Oxacillin-Resistant Staphylococcus lugdunensis Endemic in a Hospital.

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