Assessing the inflammatory response to in vitro polymicrobial wound biofilms in a skin epidermis model.

Assessing the inflammatory response to in vitro polymicrobial wound biofilms in a skin epidermis model.
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DOI:
10.1038/s41522-022-00286-z
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发表时间:
2022-04-07
影响因子:
9.2
通讯作者:
Ramage G
Ramage G
中科院分区:
生物学1区
文献类型:
--
作者:
Brown JL;Townsend E;Short RD;Williams C;Woodall C;Nile CJ;Ramage G

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伤口通常会被含有细菌和真菌微生物的多微生物生物膜感染。伤口的微生物定植会干扰充分的愈合和修复,导致某些个体的慢性化率较高,这在全球范围内可能会带来巨大的社会经济负担。缓解慢性伤口生物膜形成的一种途径是使用局部伤口清洗剂和软膏对感染区域进行充分治疗。因此,这里的主要目的是创建一个复杂的体外生物膜模型,其中包含一系列通常从感染伤口环境中分离出来的微生物。这些多微生物生物膜用三种常规的抗生物膜伤口清洗剂——氯己定(CHX)、聚维酮碘(PVP - I)和过氧化氢(H₂O₂)进行处理,并使用实时/死细胞定量聚合酶链反应(qPCR)评估对微生物的疗效。所有处理都降低了生物膜的活性,尽管发现过氧化氢是最有效的治疗方式。然后将这些生物膜与3D皮肤表皮共同培养,以评估组织内的炎症特征。在生物膜刺激后,收集了表皮的详细转录和蛋白质组图谱。在转录水平上,所有处理都将炎症标志物的表达降低到基线水平(未处理的组织对照)。欧林克(Olink)技术揭示了在未处理和经氯己定处理的生物膜刺激后组织中独特的蛋白质组反应。这突出表明临床医生的治疗选择可能取决于组织对这种生物膜治疗的反应,而不仅仅是治疗在杀死生物膜方面的有效性。
Wounds can commonly become infected with polymicrobial biofilms containing bacterial and fungal microorganisms. Microbial colonization of the wound can interfere with sufficient healing and repair, leading to high rates of chronicity in certain individuals, which can have a huge socioeconomic burden worldwide. One route for alleviating biofilm formation in chronic wounds is sufficient treatment of the infected area with topical wound washes and ointments. Thus, the primary aim here was to create a complex in vitro biofilm model containing a range of microorganisms commonly isolated from the infected wound milieu. These polymicrobial biofilms were treated with three conventional anti-biofilm wound washes, chlorhexidine (CHX), povidone-iodine (PVP-I), and hydrogen peroxide (H2O2), and efficacy against the microorganisms assessed using live/dead qPCR. All treatments reduced the viability of the biofilms, although H2O2 was found to be the most effective treatment modality. These biofilms were then co-cultured with 3D skin epidermis to assess the inflammatory profile within the tissue. A detailed transcriptional and proteomic profile of the epidermis was gathered following biofilm stimulation. At the transcriptional level, all treatments reduced the expression of inflammatory markers back to baseline (untreated tissue controls). Olink technology revealed a unique proteomic response in the tissue following stimulation with untreated and CHX-treated biofilms. This highlights treatment choice for clinicians could be dictated by how the tissue responds to such biofilm treatment, and not merely how effective the treatment is in killing the biofilm.
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