An exploration of mechanisms underlying Desemzia incerta colonization resistance to methicillin-resistant Staphylococcus aureus on the skin.
An exploration of mechanisms underlying Desemzia incerta colonization resistance to methicillin-resistant Staphylococcus aureus on the skin.
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探索 Desemzia incerta 对皮肤上耐甲氧西林金黄色葡萄球菌定植的抵抗机制。
DOI：
10.1101/2023.10.11.561853
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Grice,ElizabethA
中科院分区：
文献类型：
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作者：
Wei,Monica;Knight,SimonAb;Fazelinia,Hossein;Spruce,Lynn;Roof,Jennifer;Chu,Emily;Walsh,Jasmine;Flowers,Laurice;Kim,DanielY;Zhu,Jun;Grice,ElizabethA
耐甲氧西林金黄色葡萄球菌（MRSA）在人体皮肤和鼻孔定植，导致MRSA的社区传播。MRSA在人类和牲畜之间的传播加剧了这种传播，特别是猪。在这里，我们利用人类和猪皮肤之间的共同特征，包括共同的MRSA定植，来研究MRSA定植抗性的新型细菌介质。我们专注于研究较少的细菌物种Desemzia incerta，我们发现它通过分泌产物发挥抗菌活性，并在活体尿液皮肤模型中表现出对MRSA的定植抗性。通过平行的基因组学和生化研究，我们发现D. incertasecretes一种抗微生物蛋白。序列蛋白纯化和蛋白质组学分析确定了24个候选抑制蛋白，包括一个有前途的肽聚糖水解酶候选。借助D.与MRSA共培养时，我们发现暴露于D.不确定性导致MRSA生物膜产生减少。这些结果强调了在宿主范围内探索微生物群落的价值，这可以导致新的治疗药物以及增加对微生物竞争的理解。重要的是，耐甲氧西林金黄色葡萄球菌（MRSA）造成了重大的医疗负担，并可以通过牲畜传播传播到人群。皮肤微生物组的成员可以通过一种被称为定植抗性的知之甚少的现象来防止MRSA定植。本文研究了S.金黄色葡萄球菌细菌抑制剂先前从猪皮肤模型中鉴定。我们确定了一种猪皮寄生虫，Desemzia incerta，在小鼠模型中减少MRSA定植。我们采用基因组学、蛋白质组学和转录组学相结合的分析方法来探讨D. incertaandS.金黄色。我们确定了24个候选抗菌蛋白分泌的D。这可能是其抗菌活性的原因。我们还发现，暴露于D。不确定性导致减少。金黄色生物膜形成。这些发现表明，MRSA的家畜传播可以用来揭示MRSA定植抗性的新机制。
Colonization of human skin and nares by methicillin-resistantStaphylococcus aureus(MRSA) leads to the community spread of MRSA. This spread is exacerbated by the transfer of MRSA between humans and livestock, particularly swine. Here, we capitalized on the shared features between human and porcine skin, including shared MRSA colonization, to study novel bacterial mediators of MRSA colonization resistance. We focused on the poorly studied bacterial speciesDesemzia incerta, which we found to exert antimicrobial activity through a secreted product and exhibited colonization resistance against MRSA in anin vivomurine skin model. Using parallel genomic and biochemical investigation, we discovered thatD. incertasecretes an antimicrobial protein. Sequential protein purification and proteomics analysis identified 24 candidate inhibitory proteins, including a promising peptidoglycan hydrolase candidate. Aided by transcriptional analysis ofD. incertaand MRSA cocultures, we found that exposure toD. incertaleads to decreased MRSA biofilm production. These results emphasize the value of exploring microbial communities across a spectrum of hosts, which can lead to novel therapeutic agents as well as an increased understanding of microbial competition.IMPORTANCEMethicillin-resistantStaphylococcus aureus(MRSA) causes a significant healthcare burden and can be spread to the human population via livestock transmission. Members of the skin microbiome can prevent MRSA colonization via a poorly understood phenomenon known as colonization resistance. Here, we studied the colonization resistance ofS. aureusby bacterial inhibitors previously identified from a porcine skin model. We identify a pig skin commensal,Desemzia incerta, that reduced MRSA colonization in a murine model. We employ a combination of genomic, proteomic, and transcriptomic analyses to explore the mechanisms of inhibition betweenD. incertaandS. aureus. We identify 24 candidate antimicrobial proteins secreted byD. incertathat could be responsible for its antimicrobial activity. We also find that exposure toD. incertaleads to decreasedS. aureusbiofilm formation. These findings show that the livestock transmission of MRSA can be exploited to uncover novel mechanisms of MRSA colonization resistance.