金黄色葡萄球菌（Staphylococcus aureus LukMF）以中性粒细胞为目标，促进皮肤和软组织感染

IF 12.5 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Advances Pub Date : 2025-07-04 DOI:10.1126/sciadv.adr5240

Daiane Boff, Ravishankar Chandrasekaran, Gregory Putzel, Rachel M. Kratofil, Xuhui Zheng, Ashley Castellaw, Kody Mansfield, Ikjot Sidhu, Avantika Dhabaria, Keenan A. Lacey, Sandra Gonzalez, Filadelfia Tadjibaeva, Beatrix Ueberheide, Cynthia Loomis, Alejandro Pironti, Silva Holtfreter, Shruti Naik, Victor J. Torres

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引用次数: 0

摘要

病原体已经进化到高度适应其自然宿主。例如，社区相关性耐甲氧西林金黄色葡萄球菌USA300是导致人类皮肤和软组织感染（SSTIs）流行的一个谱系。由于其对人类的亲和性，使USA300成为主要皮肤病原体的机制仍未完全确定。通过利用啮齿动物适应的金黄色葡萄球菌菌株，我们开发了SSTIs的自然模型。我们发现LukMF '，一种与人类特异性LukSF-PV毒素同源的成孔白细胞素，在小鼠中驱动皮肤病理。LukMF通过趋化因子受体CCR1裂解中性粒细胞，进而促进感染病灶内的炎症病理和微生物存活。消融CCR1、中性粒细胞耗竭或接种LukMF都能保护小鼠免受皮肤病变。因此，这些数据支持了将杀白细胞素与人类性传播感染联系起来的流行病学研究，并强调了自然模型在发现减少感染的潜在靶点方面的力量。

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Staphylococcus aureus LukMF′ targets neutrophils to promote skin and soft tissue infection

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Staphylococcus aureus LukMF′ targets neutrophils to promote skin and soft tissue infection

Pathogens have evolved to be highly adapted to their natural host. Community-associated methicillin-resistant Staphylococcus aureus USA300, for instance, is a lineage responsible for the epidemic of skin and soft tissue infections (SSTIs) in humans. Owing to its human tropism, mechanisms that enabled the rise of USA300 as a major skin pathogen remain incompletely defined. By leveraging a rodent-adapted strain of S. aureus, we developed a natural model of SSTIs. We found that LukMF′, a pore-forming leukocidin homolog to the human-specific LukSF-PV toxin, drives skin pathology in mice. LukMF′ lyses neutrophils via the chemokine receptor CCR1, which in turn fuels inflammatory pathology and microbial survival within the infectious nidus. Ablation of CCR1, depletion of neutrophils, or vaccination with LukMF′ all protected mice from skin pathology. Thus, these data support epidemiological studies linking leukocidins with human SSTIs and highlight the power of natural models to unearth potential targets to curtail infections.

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来源期刊

Science Advances 综合性期刊-综合性期刊

CiteScore

21.40

自引率

1.50%

发文量

1937

审稿时长

29 weeks

期刊介绍： Science Advances, an open-access journal by AAAS, publishes impactful research in diverse scientific areas. It aims for fair, fast, and expert peer review, providing freely accessible research to readers. Led by distinguished scientists, the journal supports AAAS's mission by extending Science magazine's capacity to identify and promote significant advances. Evolving digital publishing technologies play a crucial role in advancing AAAS's global mission for science communication and benefitting humankind.