Institute of Medical Microbiology, Jena University Hospital, Jena, Germany.
Institute of Physiological Chemistry and Pathobiochemistry, Germany; Cells-in-Motion Cluster of Excellence, University of Muenster, Muenster, Germany.
Int J Med Microbiol. 2018 Oct;308(7):761-769. doi: 10.1016/j.ijmm.2018.05.004. Epub 2018 May 22.
Staphylococcus aureus is the most frequent pathogen causing diabetic foot infections. Here, we investigated the degree of bacterial virulence required to establish invasive tissue infections in diabetic organisms. Staphylococcal isolates from diabetic and non-diabetic foot ulcers were tested for their virulence in in vitro functional assays of host cell invasion and cytotoxicity. Isolates from diabetes mellitus type I/II patients exhibited less virulence than isolates from non-diabetic patients, but were nevertheless able to establish severe infections. In some cases, non-invasive isolates were detected deep within diabetic wounds, even though the strains were non-pathogenic in cell culture models. Testing of defined isolates in murine footpad injection models revealed that both low- and high-virulent bacterial strains persisted in higher numbers in diabetic compared to non-diabetic hosts, suggesting that hyperglycemia favors bacterial survival. Additionally, the bacterial load was higher in NOD mice, which have a compromised immune system, compared to C57Bl/6 mice. Our results reveal that high as well as low-virulent staphylococcal strains are able to cause soft tissue infections and to persist in diabetic humans and mice, suggesting a reason for the frequent and endangering infections in patients with diabetes.
金黄色葡萄球菌是引起糖尿病足感染最常见的病原体。在这里，我们研究了导致糖尿病机体发生侵袭性组织感染所需的细菌毒力程度。从糖尿病和非糖尿病足部溃疡中分离的葡萄球菌分离株在体外宿主细胞侵袭和细胞毒性的功能测定中检测其毒力。与非糖尿病患者分离株相比，I/II 型糖尿病患者的分离株的毒力较低，但仍能引起严重感染。在某些情况下，即使在细胞培养模型中这些菌株没有致病性，也会在糖尿病伤口深处检测到非侵袭性分离株。在鼠足垫注射模型中测试特定分离株表明，低毒力和高毒力细菌株在糖尿病宿主中比在非糖尿病宿主中持续存在的数量更多，这表明高血糖有利于细菌存活。此外，与 C57Bl/6 小鼠相比，免疫系统受损的 NOD 小鼠的细菌载量更高。我们的结果表明，高毒力和低毒力的葡萄球菌株均能引起软组织感染，并在糖尿病患者中持续存在，这可能是糖尿病患者频繁发生危险感染的原因。
