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<p>While <i>Staphylococcus aureus</i> is a commensal of healthy human tissue (nose and skin) it can inhabit various sites around the body to cause disease. The basis for this impressive diversity of colonization sites is a plasticity of its metabolism. This includes a switch in metabolic states when assaulted by physical or chemical stressors. Adopting quasi-dormant growth states, such as the Small Colony Variant (SCV) state, enables a sub-population of its cells to tolerate antibiotics and hide from the immune system. There have been numerous studies on clinical samples and isolates of <i>S. aureus</i> which have investigated the genetic changes as cells shift to a SCV state. It is clinically important to understand how <i>S. aureus</i> in patients with diabetic foot ulcers (DFU) proceed to infections and then progress into the bone (osteomyelitis). We have assaulted such isolates using different assays and antibiotics (including ciprofloxacin, tobramycin, rifampicin and oxacillin) and have seen that in some cases, strains switch to alternative colony types (white colony variants (WCV) and SCVs). We then applied metabolomics profiling to investigate the changes in metabolic pathways in these alternative cell types compared to their parental <i>S. aureus</i>. We noted, regardless of source of isolate or antibiotic stress, these cells possessed common metabolic pathways that were lowered in activity such as TCA cycle, alanine and aspartate metabolism, and glycine metabolism.</p>

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Metabolomics to characterise changes within small colony variants of Staphylococcus aureus that have been induced by antibiotics

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月10日

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  • Lixing Xu,
  • Stephen P. Kidd

摘要

While Staphylococcus aureus is a commensal of healthy human tissue (nose and skin) it can inhabit various sites around the body to cause disease. The basis for this impressive diversity of colonization sites is a plasticity of its metabolism. This includes a switch in metabolic states when assaulted by physical or chemical stressors. Adopting quasi-dormant growth states, such as the Small Colony Variant (SCV) state, enables a sub-population of its cells to tolerate antibiotics and hide from the immune system. There have been numerous studies on clinical samples and isolates of S. aureus which have investigated the genetic changes as cells shift to a SCV state. It is clinically important to understand how S. aureus in patients with diabetic foot ulcers (DFU) proceed to infections and then progress into the bone (osteomyelitis). We have assaulted such isolates using different assays and antibiotics (including ciprofloxacin, tobramycin, rifampicin and oxacillin) and have seen that in some cases, strains switch to alternative colony types (white colony variants (WCV) and SCVs). We then applied metabolomics profiling to investigate the changes in metabolic pathways in these alternative cell types compared to their parental S. aureus. We noted, regardless of source of isolate or antibiotic stress, these cells possessed common metabolic pathways that were lowered in activity such as TCA cycle, alanine and aspartate metabolism, and glycine metabolism.