Coagulase-negative staphylococci (CoNS) and Staphylococcus aureus are part of the natural flora of humans and other mammals. We found that spent media from the CoNS species Staphylococcus caprae can inhibit agr-mediated quorum sensing by all classes of S. aureus. A biochemical assessment of the inhibitory activity suggested that the S. caprae autoinducing peptide (AIP) was responsible, and mass spectrometric analysis identified the S. caprae AIP as an eight-residue peptide (YSTCSYYF). Using a murine model of intradermal MRSA infection, the therapeutic efficacy of synthetic S. caprae AIP was evident by a dramatic reduction in both dermonecrotic injury and cutaneous bacterial burden relative to controls. Competition experiments between S. caprae and MRSA demonstrated a significant reduction in MRSA burden using murine models of both skin colonization and intradermal infection. Our findings indicate that important interactions occur between commensals that can impact disease outcomes and potentially shape the composition of the natural flora.

凝固酶阴性葡萄球菌 (CoNS) 和金黄色葡萄球菌是人类和其他哺乳动物自然菌群的一部分。我们发现来自 CoNS 物种山羊葡萄球菌的废培养基可以抑制所有金黄色葡萄球菌类别的agr介导的群体感应。对抑制活性的生化评估表明，山羊链球菌自诱导肽（AIP）是起作用的，并且质谱分析确定山羊链球菌AIP是八残基肽（YSTCSYYF）。使用皮内 MRSA 感染的小鼠模型，合成山羊葡萄球菌AIP 的治疗效果显而易见，与对照相比，皮肤坏死损伤和皮肤细菌负荷显着减少。山羊链球菌和 MRSA之间的竞争实验表明，使用皮肤定植和皮内感染的小鼠模型，MRSA 负担显着减少。我们的研究结果表明，共生体之间发生了重要的相互作用，可以影响疾病结果并可能塑造自然菌群的组成。