Kim Jane H, Ruegger Paul R, Lebig Elyson Gavin, VanSchalkwyk Samantha, Jeske Daniel R, Hsiao Ansel, Borneman James, Martins-Green Manuela
Molecular, Cell and Systems Biology Department, University of California, Riverside, Riverside, CA, United States.
Microbiology and Plant Pathology Department, University of California, Riverside, Riverside, CA, United States.
Front Cell Infect Microbiol. 2020 Jun 3;10:259. doi: 10.3389/fcimb.2020.00259. eCollection 2020.
Diabetics chronic wounds are characterized by high levels of oxidative stress (OS) and are often colonized by biofilm-forming bacteria that severely compromise healing and can result in amputation. However, little is known about the role of skin microbiota in wound healing and chronic wound development. that high OS levels lead to chronic wound development by promoting the colonization of biofilm-forming bacteria over commensal/beneficial bacteria. To test this hypothesis, we used our mouse model for chronic wounds where pathogenic biofilms develop naturally after induction of high OS immediately after wounding. We sequenced the bacterial rRNA internal transcribed spacer (ITS) gene of the wound microbiota from wound initiation to fully developed chronic wounds. Indicator species analysis, which considers a species' fidelity and specificity, was used to determine which bacterial species were strongly associated with healing wounds or chronic wounds. We found that healing wounds were colonized by a diverse and dynamic bacterial microbiome that never developed biofilms even though biofilm-forming bacteria were present. Several clinically relevant species that are present in human chronic wounds, such as sp., sp., and , were highly associated with healing wounds. These bacteria may serve as bioindicators of healing and may actively participate in the processes of wound healing and preventing pathogenic bacteria from colonizing the wound. In contrast, chronic wounds, which had high levels of OS, had low bacterial diversity and were colonized by several clinically relevant, biofilm-forming bacteria such as , and sp. We observed unique population trends: for example, associated with aggressive biofilm development, whereas was only present early after injury. These findings show that high levels of OS in the wound significantly altered the bacterial wound microbiome, decreasing diversity and promoting the colonization of bacteria from the skin microbiota to form biofilm. , bacteria associated with non-chronic or chronic wounds could function as bioindicators of healing or non-healing (chronicity), respectively. Moreover, a better understanding of bacterial interactions between pathogenic and beneficial bacteria within an evolving chronic wound microbiota may lead to .
糖尿病患者的慢性伤口具有高水平的氧化应激(OS)特征,并且常常被形成生物膜的细菌定植,这些细菌严重损害伤口愈合并可能导致截肢。然而,关于皮肤微生物群在伤口愈合和慢性伤口发展中的作用知之甚少。有研究认为高OS水平通过促进形成生物膜的细菌而非共生/有益细菌的定植导致慢性伤口的发展。为了验证这一假设,我们使用了慢性伤口小鼠模型,在受伤后立即诱导高OS,致病生物膜会自然形成。我们对从伤口起始到完全发展为慢性伤口的伤口微生物群的细菌rRNA内转录间隔区(ITS)基因进行了测序。使用考虑物种保真度和特异性的指示物种分析来确定哪些细菌物种与愈合伤口或慢性伤口密切相关。我们发现愈合伤口被多样且动态的细菌微生物群定植,即使存在形成生物膜的细菌,也从未形成生物膜。人类慢性伤口中存在的几种临床相关物种,如某某菌、某某菌和某某菌,与愈合伤口高度相关。这些细菌可能作为愈合的生物指标,并可能积极参与伤口愈合过程以及防止病原菌定植于伤口。相比之下,具有高OS水平的慢性伤口细菌多样性低,并被几种临床相关的形成生物膜的细菌定植,如某某菌、某某菌和某某菌。我们观察到独特的种群趋势:例如,某某菌与侵袭性生物膜形成相关,而某某菌仅在受伤后早期出现。这些发现表明伤口中的高OS水平显著改变了伤口细菌微生物群,降低了多样性并促进了皮肤微生物群中的细菌定植以形成生物膜。此外,与非慢性或慢性伤口相关的细菌可分别作为愈合或不愈合(慢性)的生物指标。此外,更好地理解不断演变的慢性伤口微生物群中致病细菌和有益细菌之间的相互作用可能会带来……