Variable staphyloxanthin production by Staphylococcus aureus drives strain-dependent effects on diabetic wound-healing outcomes.
Variable staphyloxanthin production by Staphylococcus aureus drives strain-dependent effects on diabetic wound-healing outcomes.
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DOI：
10.1016/j.celrep.2023.113281
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发表时间：
2023-10-31
期刊：
影响因子：
8.8
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中科院分区：
文献类型：
--
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金黄色葡萄球菌的菌株水平变异是导致皮肤病和慢性伤口疾病负担和临床结局的一个因素。然而，驱动这些可变的主机响应的微生物机制知之甚少。为了确定菌株特异性结果的潜在机制，我们对S.从糖尿病足溃疡培养的金黄色葡萄球菌分离物。来自不愈合伤口的分离物产生更多的葡萄黄素，一种细胞膜色素。在小鼠糖尿病伤口中，与葡萄球菌缺陷型菌株相比，葡萄球菌产生型菌株显著延迟伤口闭合。葡萄球菌黄素促进抗氧化应激和增强细菌在中性粒细胞中的存活。对具有不同葡萄球菌黄素表型的遗传相似的临床分离株进行比较基因组学和转录组学分析，揭示了sigma B操纵子的突变，导致应激反应基因表达的显著差异。我们的工作说明了一个框架，以确定性状的基础菌株水平变化的疾病负担，并提出了更精确的目标，治疗干预S。金色阳性伤口坎贝尔等人研究了S.从糖尿病伤口培养的金黄色葡萄球菌分离物。葡萄黄素是一种黄色抗氧化色素，其产生与延迟愈合有关。作为人类糖尿病伤口中菌株特异性结果的潜在机制，葡萄球菌黄素促进细菌存活并损害小鼠糖尿病伤口愈合。
Strain-level variation in Staphylococcus aureus is a factor that contributes to disease burden and clinical outcomes in skin disorders and chronic wounds. However, the microbial mechanisms that drive these variable host responses are poorly understood. To identify mechanisms underlying strain-specific outcomes, we perform high-throughput phenotyping screens on S. aureus isolates cultured from diabetic foot ulcers. Isolates from non-healing wounds produce more staphyloxanthin, a cell membrane pigment. In murine diabetic wounds, staphyloxanthin-producing isolates delay wound closure significantly compared with staphyloxanthin-deficient isolates. Staphyloxanthin promotes resistance to oxidative stress and enhances bacterial survival in neutrophils. Comparative genomic and transcriptomic analysis of genetically similar clinical isolates with disparate staphyloxanthin phenotypes reveals a mutation in the sigma B operon, resulting in marked differences in stress response gene expression. Our work illustrates a framework to identify traits that underlie strain-level variation in disease burden and suggests more precise targets for therapeutic intervention in S. aureus-positive wounds. Campbell et al. investigate the phenotypic and genomic diversity of S. aureus isolates cultured from diabetic wounds. Production of staphyloxanthin, a yellow antioxidant pigment, associates with delayed healing. Identified as a mechanism underlying strain-specific outcomes in human diabetic wounds, staphyloxanthin promotes bacterial survival and impairs murine diabetic wound healing.
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影响因子：
3.1
作者：
Dale, SE;Doherty-Kirby, A;Heinrichs, DE
通讯作者：
Heinrichs, DE
影响因子：
5.2
作者：
Everett E;Mathioudakis N
通讯作者：
Mathioudakis N
影响因子：
2.7
作者：
Gardiner M;Vicaretti M;Sparks J;Bansal S;Bush S;Liu M;Darling A;Harry E;Burke CM
通讯作者：
Burke CM
影响因子：
14.9
作者：
Haft DH;DiCuccio M;Badretdin A;Brover V;Chetvernin V;O'Neill K;Li W;Chitsaz F;Derbyshire MK;Gonzales NR;Gwadz M;Lu F;Marchler GH;Song JS;Thanki N;Yamashita RA;Zheng C;Thibaud-Nissen F;Geer LY;Marchler-Bauer A;Pruitt KD
通讯作者：
Pruitt KD
影响因子：
6.4
作者：
Fey PD;Endres JL;Yajjala VK;Widhelm TJ;Boissy RJ;Bose JL;Bayles KW
通讯作者：
Bayles KW