Department of Dermatology & Microbiology, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania, USA.
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania , Philadelphia, Pennsylvania, USA.
mSphere. 2023 Aug 24;8(4):e0017723. doi: 10.1128/msphere.00177-23. Epub 2023 Jul 5.
The microbiota mediate multiple aspects of skin barrier function, including colonization resistance to pathogens such as . The endogenous skin microbiota limits colonization via competition and direct inhibition. Novel mechanisms of colonization resistance are promising therapeutic targets for drug-resistant infections, such as those caused by methicillin-resistant (MRSA). Here, we developed and characterized a swine model of topical microbiome perturbation and MRSA colonization. As in other model systems, topical antimicrobial treatment had a little discernable effect on community diversity though the overall microbial load was sensitive to multiple types of intervention, including swabbing. In parallel, we established a porcine skin culture collection and screened 7,700 isolates for MRSA inhibition. Using genomic and phenotypic criteria, we curated three isolates to investigate whether prophylactic colonization would inhibit MRSA colonization . The three-member consortium together, but not individually, provided protection against MRSA colonization, suggesting cooperation and/or synergy among the strains. Inhibitory isolates were represented across all major phyla of the pig skin microbiota and did not have a strong preference for inhibiting closely related species, suggesting that relatedness is not a condition of antagonism. These findings reveal the porcine skin as an underexplored reservoir of skin commensal species with the potential to prevent MRSA colonization and infection. IMPORTANCE The skin microbiota is protective against pathogens or opportunists such as , the most common cause of skin and soft tissue infections. can colonize normal skin and nasal passages, and colonization is a risk factor for infection, especially on breach of the skin barrier. Here, we established a pig model to study the competitive mechanisms of the skin microbiota and their role in preventing colonization by MRSA. This drug-resistant strain is also a livestock pathogen, and swine herds can be reservoirs of MRSA carriage. From 7,700 cultured skin isolates, we identified 37 unique species across three phyla that inhibited MRSA. A synthetic community of three inhibitory isolates provided protection together, but not individually, in a murine model of MRSA colonization. These findings suggest that antagonism is widespread in the pig skin microbiota, and these competitive interactions may be exploited to prevent MRSA colonization.
微生物组介导皮肤屏障功能的多个方面，包括对 等病原体的定植抵抗。内源性皮肤微生物组通过竞争和直接抑制来限制 定植。定植抵抗的新机制是治疗耐药感染（如耐甲氧西林金黄色葡萄球菌（MRSA）引起的感染）的有前途的治疗靶点。在这里，我们开发并表征了一种猪模型，用于研究局部微生物组扰动和 MRSA 定植。与其他模型系统一样，局部抗菌治疗对群落多样性几乎没有明显影响，尽管整体微生物负荷对多种干预措施（包括擦拭）敏感。同时，我们建立了猪皮肤培养物集合，并筛选了 7700 个分离物以抑制 MRSA。使用基因组和表型标准，我们培养了三个分离物以研究预防性定植是否会抑制 MRSA 定植。三个成员的联合体共同但不是单独地提供了对 MRSA 定植的保护，表明菌株之间存在合作和/或协同作用。抑制性分离物代表了猪皮肤微生物组的所有主要门，并且对抑制密切相关的物种没有强烈的偏好，这表明亲缘关系不是拮抗作用的条件。这些发现揭示了猪皮肤作为具有预防 MRSA 定植和感染潜力的未充分探索的皮肤共生物种的储存库。
重要性皮肤微生物组可防止 等病原体或机会主义者定植， 是皮肤和软组织感染的最常见原因。 可以定植于正常皮肤和鼻腔，定植是感染的危险因素，尤其是在皮肤屏障受损时。在这里，我们建立了一个猪模型来研究皮肤微生物组的竞争机制及其在预防 MRSA 定植中的作用。这种耐药菌株也是一种牲畜病原体，猪群可能是 MRSA 携带的储库。从 7700 个培养的皮肤分离物中，我们在三个门中鉴定出了 37 个独特的抑制 MRSA 的物种。三个抑制性分离物的合成群落一起提供了保护，但不是单独的，在 MRSA 定植的小鼠模型中。这些发现表明，拮抗作用在猪皮肤微生物组中广泛存在，这些竞争相互作用可能被利用来预防 MRSA 定植。
