Genotypic variations between wild-type and small colony variant of Staphylococcus aureus in prosthetic valve infectious endocarditis: a comparative genomic and transcriptomic analysis.
Staphylococcus aureus small colony variants (SCVs) can cause persistent infections. However, the genomes and transcriptomes of S. aureus SCVs remain poorly understood. A pair of isogenic wild-type and SCV methicillin-resistant S. aureus (MRSA) strains (IE1 and IE2, respectively) were isolated from a patient with prosthetic valve infectious endocarditis. The SCV strain IE2 grew more slowly than the wild-type strain, and serum killing and mouse lethality assays revealed that the virulence of SCV strain IE2 was decreased. Whole-genome sequencing of the SCV and wild-type strains revealed 15 mutations in nine genes associated with metabolism, virulence and DNA repair, including serine/threonine-protein kinase PrkC (prkC), glycerol-3-phosphate acyltransferase (plsY), 2-deoxyribose-5-phosphate aldolase (deoC), extracellular adherence protein (eap), iron compound ABC uptake transporter substrate-binding protein (sstD), RecU Holliday junction resolvase (recU), excinuclease ABC subunit B (uvrB), type I restriction-modification system, M subunit (hsdM) and smooth muscle caldesmon. Sequencing of RNA transcripts revealed that expression levels of 321 genes were upregulated and 582 genes were downregulated in SCV strain IE2 compared with IE1. Most of the differentially expressed genes were involved in metabolism. Expression levels of several genes involved in the pathways to which plsY, deoC, eap and sstD belonged were changed, associated with the metabolism and virulence of S. aureus. In conclusion, the reduced growth rate and decreased virulence of MRSA SCV strains may be related to mutations in and downregulation of genes associated with metabolism and virulence, especially plsY, deoC, eap and sstD.
['Chen|Hongbin|H|', 'Wang|Qi|Q|', 'Yin|Yuyao|Y|', 'Li|Shuguang|S|', 'Niu|Deng-Ke|DK|', 'Wang|Hui|H|']
D000818:Animals D000900:Anti-Bacterial Agents D001426:Bacterial Proteins D002438:Cefoperazone D004696:Endocarditis D005260:Female D020869:Gene Expression Profiling D016680:Genome, Bacterial D005838:Genotype D006350:Heart Valve Prosthesis D006801:Humans D008297:Male D055624:Methicillin-Resistant Staphylococcus aureus D051379:Mice D008807:Mice, Inbred BALB C D020641:Polymorphism, Single Nucleotide D013203:Staphylococcal Infections D013407:Sulbactam D059467:Transcriptome D014640:Vancomycin D014774:Virulence D065093:beta-Lactamase Inhibitors
Small colony variant Staphylococcus aureus Prosthetic valve infectious endocarditis Whole-genome sequencing RNA-Seq