Department of Surgery, IU Health Comprehensive Wound Center, Indiana Center for Regenerative Medicine and Engineering, Indiana University School of Medicine, Indianapolis, IN.
Comprehensive Wound Center, The Ohio State University, Columbus, OH.
Ann Surg. 2020 Jun;271(6):1174-1185. doi: 10.1097/SLA.0000000000003053.
The objective of this work was to causatively link biofilm properties of bacterial infection to specific pathogenic mechanisms in wound healing.
Staphylococcus aureus is one of the four most prevalent bacterial species identified in chronic wounds. Causatively linking wound pathology to biofilm properties of bacterial infection is challenging. Thus, isogenic mutant stains of S. aureus with varying degree of biofilm formation ability was studied in an established preclinical porcine model of wound biofilm infection.
Isogenic mutant strains of S. aureus with varying degree (ΔrexB > USA300 > ΔsarA) of biofilm-forming ability were used to infect full-thickness porcine cutaneous wounds.
Compared with that of ΔsarA infection, wound biofilm burden was significantly higher in response to ΔrexB or USA300 infection. Biofilm infection caused degradation of cutaneous collagen, specifically collagen 1 (Col1), with ΔrexB being most pathogenic in that regard. Biofilm infection of the wound repressed wound-edge miR-143 causing upregulation of its downstream target gene matrix metalloproteinase-2. Pathogenic rise of collagenolytic matrix metalloproteinase-2 in biofilm-infected wound-edge tissue sharply decreased collagen 1/collagen 3 ratio compromising the biomechanical properties of the repaired skin. Tensile strength of the biofilm infected skin was compromised supporting the notion that healed wounds with a history of biofilm infection are likely to recur.
This study provides maiden evidence that chronic S. aureus biofilm infection in wounds results in impaired granulation tissue collagen leading to compromised wound tissue biomechanics. Clinically, such compromise in tissue repair is likely to increase wound recidivism.
本研究旨在将细菌感染的生物膜特性与伤口愈合中的特定发病机制建立因果关系。
金黄色葡萄球菌是慢性伤口中最常见的四种细菌之一。将伤口病理学与细菌感染的生物膜特性建立因果关系具有挑战性。因此，在建立的猪慢性伤口生物膜感染临床前模型中，研究了具有不同生物膜形成能力的金黄色葡萄球菌同源突变株。
使用具有不同生物膜形成能力（ΔrexB>USA300>ΔsarA）的金黄色葡萄球菌同源突变株感染全层猪皮肤伤口。
与ΔsarA 感染相比，ΔrexB 或 USA300 感染后的伤口生物膜负担明显更高。生物膜感染导致皮肤胶原，特别是胶原 1（Col1）降解，其中ΔrexB 最具致病性。伤口边缘的 miR-143 被生物膜感染抑制，导致其下游靶基因基质金属蛋白酶-2 的上调。生物膜感染伤口边缘组织中胶原酶基质金属蛋白酶-2 的致病性升高，导致胶原 1/胶原 3 比值急剧下降，从而破坏修复皮肤的生物力学特性。生物膜感染皮肤的拉伸强度降低，这支持了有生物膜感染史的愈合伤口可能会再次复发的观点。
本研究首次提供证据表明，慢性金黄色葡萄球菌生物膜感染伤口会导致肉芽组织胶原减少，从而导致伤口组织生物力学受损。临床上，这种组织修复的缺陷可能会增加伤口复发的风险。
