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Development of a novel core genome MLST scheme for tracing multidrug resistant Staphylococcus capitis.

ABSTRACT: Staphylococcus capitis, which causes bloodstream infections in neonatal intensive care units, is a common cause of healthcare-associated infections. Thus, a standardized high-resolution typing method to document the transmission and dissemination of multidrug-resistant S. capitis isolates is required. We aimed to establish a core genome multilocus sequence typing (cgMLST) scheme to surveil S. capitis. The cgMLST scheme was defined based on primary and validation genome sets and tested with outbreaks of linezolid-resistant isolates and a validation set. Phylogenetic analysis was performed to investigate the population structure and compare it with the result of cgMLST analysis. The S. capitis population consists of 1 dominant, NRCS-A, and 4 less common clones. In this work, a multidrug-resistant clone (L clone) with linezolid resistance is identified. With the features of type III SCCmec and multiple copies of mutations of G2576T and C2104T in the 23S rRNA, the L clone has been spreading silently across China.

SUBMITTER: Wang Z

PROVIDER: S-EPMC9307846 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Development of a novel core genome MLST scheme for tracing multidrug resistant Staphylococcus capitis.

Wang Zhengan Z Gu Chao C Sun Lu L Zhao Feng F Fu Ying Y Di Lingfang L Zhang Junxiong J Zhuang Hemu H Jiang Shengnan S Wang Haiping H Zhu Feiteng F Chen Yiyi Y Chen Mengzhen M Ling Xia X Chen Yan Y Yu Yunsong Y

Nature communications 20220722 1

Staphylococcus capitis, which causes bloodstream infections in neonatal intensive care units, is a common cause of healthcare-associated infections. Thus, a standardized high-resolution typing method to document the transmission and dissemination of multidrug-resistant S. capitis isolates is required. We aimed to establish a core genome multilocus sequence typing (cgMLST) scheme to surveil S. capitis. The cgMLST scheme was defined based on primary and validation genome sets and tested with outbr ...[more]

PMID: 35869070

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Project description:BackgroundBacteria undergo adaptive mutation in the host. However, the specific effect of antimicrobial use on bacterial evolution and genome mutations related to bacterial survival within a patient is unclear.Materials and methodsThree S. capitis strains were sequentially isolated from cerebrospinal fluid of a clinical inpatient. Antimicrobial susceptibility, growth rate, biofilm formation and whole blood survival of these strains were measured. Relative fitness was calculated. The virulence was examined in the Galleria mellonella model. Whole-genome sequencing and in silico analysis were performed to explore the genetic mechanisms of the changes in antimicrobial resistance phenotype. Hypothetical proteins are cloned, expressed and characterized by detection the susceptibility to gentamycin.ResultsThe first isolate was susceptible to rifampin (MIC=0.25 μg/mL), resistant to gentamicin (MIC=16 μg/mL), while the later two isolates were resistant to rifampin (MIC >64 μg/mL), susceptible to gentamicin (MIC=4 μg/mL). For the latter two strains, compared to the first, frameshift mutation in a hypothetical protein encoding gene and base substitutions (in genes saeR, moaA and rpoB) were discovered. The mutation of rpoB gene caused rifampicin resistance. Mutations in saeR, moaA and hypothetical gene are associated with changes in other biological traits. Amino acid sequence-based structure and function identification of the hypothetical protein indicated that a mutation in the encoding gene might be associated with altered aminoglycoside susceptibility. Growth curve showed that the later two isolates grew faster than the first isolate with a positive fitness advantage of 13.5%, and 14.8%, accordingly. Biofilm form ability and whole blood survival of the derivative mutants were also enhanced. No significant differences of virulence in the G. mellonella model were observed.ConclusionWe report here for the first time that short-term clinical antibiotic use was associated with resistance mutations, collateral sensitivity, and positive in vivo fitness advantages to S. capitis during infection.

Dataset Information

Development of a novel core genome MLST scheme for tracing multidrug resistant Staphylococcus capitis.

Publications

Development of a novel core genome MLST scheme for tracing multidrug resistant Staphylococcus capitis.

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