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Sequence type 8 as an emerging clone of methicillin-resistant Staphylococcus aureus causing bloodstream infections in Taiwan.

ABSTRACT: Sequence type (ST) 8 has not been a common methicillin-resistant Staphylococcus aureus (MRSA) clone in Asia until recently. We aimed to determine the clinical significance and microbiological characteristics of MRSA bacteraemia (MRSAB) caused by ST8 and other endemic clones. A total of 281 non-duplicated MRSAB were identified in a medical centre between 2016 and 2018. Sequencing of target genes was performed to determine ST and to confirm ST8 belonging to USA300. Antimicrobial susceptibility testing was performing by using Sensititre standard panel. In total, ST8 accounted for 18.5% of MRSAB ranking after ST239 (31.0%) and ST59 (23.5%). However, it increased to become the most prevalent clone finally. All ST8 isolates belonged to spa clonal complex008, and carried SCCmec IV/IVa, PVL and ACME genes, indicating USA300. ST8/USA300 isolates were highly susceptible to non-β-lactams antibiotics, except fluoroquinolone and erythromycin. ST8/USA300 MRSAB is commonly developed in community settings with either healthcare risks or not (71.2%). Compared to other STs MRSAB, ST8/USA300 MRSAB patients had more diabetes mellitus (50.0%), more admitted from long-term care facility residents (25.0%), had more skin ad soft tissue infection as primary focus (25.0%), and had fewer vascular devices (26.9%) at MRSAB onset. On multivariable analysis, isolates with vancomycin MIC were significantly associated with mortality in the dose-response relationship, rather than STs. This report depicts the clinical features of ST8/USA300 MRSAB and clonal shift from prior endemic clones to ST8/USA300. Our data strongly support long-term surveillance to ascertain whether ST8/USA300 will successfully disseminate and demonstrate its pathogenicity on clinical outcomes.

SUBMITTER: Chen PY

PROVIDER: S-EPMC8475108 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundBloodstream infections due to Staphylococcus aureus cause significant patient morbidity and mortality worldwide. Of major concern is the emergence and spread of methicillin-resistant S. aureus (MRSA) in bloodstream infections, which are associated with therapeutic failure and increased mortality.MethodsWe generated high quality draft genomes from 323 S. aureus blood culture isolates from patients diagnosed with bloodstream infection at the Dartmouth-Hitchcock Medical Center, New Hampshire, USA in 2010-2018.ResultsIn silico detection of antimicrobial resistance genes revealed that 133/323 isolates (41.18%) carry horizontally acquired genes conferring resistance to at least three antimicrobial classes, with resistance determinants for aminoglycosides, beta-lactams and macrolides being the most prevalent. The most common resistance genes were blaZ and mecA, which were found in 262/323 (81.11%) and 104/323 (32.20%) isolates, respectively. Majority of the MRSA (102/105 isolates or 97.14%) identified using in vitro screening were related to two clonal complexes (CC) 5 and 8. The two CCs emerged in the New Hampshire population at separate times. We estimated that the time to the most recent common ancestor of CC5 was 1973 (95% highest posterior density (HPD) intervals: 1966-1979) and 1946 for CC8 (95% HPD intervals: 1924-1959). The effective population size of CC8 increased until the late 1960s when it started to level off until late 2000s. The levelling off of CC8 in 1968 coincided with the acquisition of SCCmec Type IV in majority of the strains. The plateau in CC8 also coincided with the acceleration in the population growth of CC5 carrying SCCmec Type II in the early 1970s, which eventually leveled off in the early 1990s. Lastly, we found evidence for frequent recombination in the two clones during their recent clonal expansion, which has likely contributed to their success in the population.ConclusionsWe conclude that the S. aureus population was shaped mainly by the clonal expansion, recombination and co-dominance of two major MRSA clones in the last five decades in New Hampshire, USA. These results have important implications on the development of effective and robust strategies for intervention, control and treatment of life-threatening bloodstream infections.

Project description:Methicillin-resistant Staphylococcus aureus (MRSA) sequence type 45 (ST45) was rarely found in China. This study was conducted to trace the transmission and evolution of emerging MRSA ST45 strains in mainland China and explore its virulence. A total of 27 ST45 isolates were included for whole-genome sequencing and genetic characteristic analysis. Epidemiological results showed that MRSA ST45 isolates were often obtained from blood, primarily originated in Guangzhou, and carried diverse virulence and drug resistance genes. Staphylococcal cassette chromosome mec type IV (SCCmec IV) dominated in MRSA ST45 (23/27, 85.2%). ST45-SCCmec V was located on a phylogenetic clade distinct from the SCCmec IV cluster. We selected two representative isolates, MR370 (ST45-SCCmec IV) and MR387 (ST45-SCCmec V), and performed hemolysin activity, a blood killing assay, a Galleria mellonella infection model, and a mouse bacteremia model, as well as real-time fluorescence quantitative PCR. MR370 was proved to have extreme virulence in the phenotypic assays and at the mRNA level compared with ST59, ST5, and USA300 MRSA strains. MR387 was comparable to USA300-LAC on the phenotype and was verified to have higher expression of scn, chp, sak, saeR, agrA, and RNAIII than USA300-LAC. The results emphasized the extraordinary performance of MR370 and the good potential of MR387 in virulence causing bloodstream infection. Meanwhile, we conclude that China MRSA ST45 showed two different clonotypes, which may be widespread in the future. The entire study is valuable as a timely reminder and reports virulence phenotypes of China MRSA ST45 for the first time. IMPORTANCE Methicillin-resistant Staphylococcus aureus ST45 is epidemic worldwide. This study contributed to the awareness of the Chinese hyper-virulent MRSA ST45 strains and served as a timely reminder of its wide dissemination of clonotypes. Further, we provide novel insights for prevention from the perspective of bloodstream infections. ST45-SCCmec V is a clonotype deserving special attention in China, and we performed genetic and phenotypic analyses for the first time on it.

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Sequence type 8 as an emerging clone of methicillin-resistant Staphylococcus aureus causing bloodstream infections in Taiwan.

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