Abstract
Though a definitive link between small colony variants (SCVs) and implant-related staphylococcal infections has been well-established, the specific underlying mechanism remains an ill-explored field. The present study analyzes the role SCVs play in catheter infection by performing genomic and metabolic analyses, as well as analyzing biofilm formation and impacts of glycine on growth and peptidoglycan-linking rate, on a clinically typical Staphylococcus epidermidis case harboring stable SCV, normal counterpart (NC) and nonstable SCV. Our findings reveal that S. epidermidis stable SCV carries mutations involved in various metabolic processes. Metabolome analyses demonstrate that two biosynthetic pathways are apparently disturbed in SCV. One is glycine biosynthesis, which contributes to remarkable glycine shortage, and supplementation of glycine restores growth and peptidoglycan-linking rate of SCV. The other is overflow of pyruvic acid and acetyl-CoA, leading to excessive acetate. SCV demonstrates higher biofilm-forming ability due to rapid autolysis and subsequent eDNA release. Despite a remarkable decline in cell viability, SCV can facilitate in vitro biofilm formation and in vivo survival of NC when co-infected with its normal counterparts. This work illustrates an intriguing strategy utilized by a glycine-auxotrophic clinical S. epidermidis SCV isolate to facilitate biofilm-related infections, and casts a new light on the role of SCV in persistent infections.
Highlights
Though a definitive link between small colony variants (SCVs) and implant-related staphylococcal infections has been well-established, the specific underlying mechanism remains an ill-explored field
21.9% of catheter infections were due to multispecies, the most common coinfection pattern was S. epidermidis related (14/28, 50%), which further demonstrates the dominant role of S. epidermidis in catheter infections (Fig. 1a)
Collectively, the present work deciphers a unique and intriguing strategy exploited by a glycine-auxotrophic clinical S. epidermidis stable SCV isolate in the persistence of biofilm-related infections (Fig. 8)
Summary
Though a definitive link between small colony variants (SCVs) and implant-related staphylococcal infections has been well-established, the specific underlying mechanism remains an ill-explored field. The present study analyzes the role SCVs play in catheter infection by performing genomic and metabolic analyses, as well as analyzing biofilm formation and impacts of glycine on growth and peptidoglycan-linking rate, on a clinically typical Staphylococcus epidermidis case harboring stable SCV, normal counterpart (NC) and nonstable SCV. With the advent of the omics era, the burgeoning omics technologies have provided a wider scope of information about SCVs, highlighting the fact that the proteomic and mutational profiles of clinical SCVs are both distinct from and more complicated than those of genetically defined ETC mutants[33,34] Such diversity in their phenotypes further underscores the significance of clinical SCVs based investigation, which is more clinically relevant and translatable to the management of persistent infections associated with SCVs. Metabolic dysfunction and SCVs have always been inextricably intertwined[35,36]. Inexplicable phenotypes of clinical SCVs still persist[22,38], indicating that the currently known mechanisms underlying the pathogenicity of SCVs are far from being comprehensive
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