Pseudomonas Aeruginosa Theft Biofilm Require Host Lipids of Cutaneous Wound.
Pseudomonas Aeruginosa Theft Biofilm Require Host Lipids of Cutaneous Wound.
复制标题
DOI：
10.1097/sla.0000000000005252
复制
发表时间：
2023-03-01
影响因子：
9
通讯作者：
中科院分区：
文献类型：
--
作者：
这项工作解决了伤口感染的复杂性，旨在测试细菌病原体铜绿假单胞菌（PA）对宿主皮肤脂质的依赖性，以形成具有病理后果的生物膜。PA生物膜导致伤口慢性化。CDC和NIH都认为生物膜感染是导致伤口慢性化的威胁。下肢慢性创伤常导致截肢手术。使用经PA或铜绿假单胞菌神经酰胺酶突变体（PA β Cer）感染的已建立的临床前猪慢性伤口生物膜模型。我们观察到细菌从宿主脂质中汲取资源以诱导PA神经酰胺酶表达三个数量级。PA利用宿主神经酰胺催化剂的产物来增强PA神经酰胺酶的转录。生物膜的形成更强大的PA相比，PA CANCer。这种代谢的下游产物如鞘氨醇和鞘氨醇-1-磷酸分别直接参与神经酰胺酶的诱导和过氧化物酶体增殖物激活受体（PPAR）δ的抑制。PA生物膜以陶瓷-艾达斯汀敏感的方式也通过诱导miR-106 b沉默PPAR δ。低的PPAR δ限制ABCA 12表达，导致皮肤脂质稳态的破坏。伤口部位的屏障功能因此受损。这项工作表明，微生物病原体必须增选宿主皮肤脂质释放生物膜致病性。抗生物膜策略不一定总是靶向微生物，靶向有感染风险的宿主脂质可能是有效的。这项工作可以被视为第一步，奠定基本的机械基础，朝着生物膜管理的范式转变。
This work addressing complexities in wound infection, seeks to test the reliance of bacterial pathogen Pseudomonas aeruginosa (PA) on host skin lipids to form biofilm with pathological consequences. PA biofilm causes wound chronicity. Both CDC as well as NIH recognizes biofilm infection as a threat leading to wound chronicity. Chronic wounds on lower extremities often lead to surgical limb amputation. An established preclinical porcine chronic wound biofilm model, infected with PA or Pseudomonas aeruginosa ceramidase mutant (PA∆Cer), was used. We observed that bacteria drew resource from host lipids to induce PA ceramidase expression by three orders of magnitude. PA utilized product of host ceramide catabolism to augment transcription of PA ceramidase. Biofilm formation was more robust in PA compared to PA∆Cer. Downstream products of such metabolism such as sphingosine and sphingosine-1-phosphate were both directly implicated in the induction of ceramidase and inhibition of peroxisome proliferator-activated receptor (PPAR)δ, respectively. PA biofilm, in a ceram-idastin-sensitive manner, also silenced PPARδ via induction of miR-106b. Low PPARδ limited ABCA12 expression resulting in disruption of skin lipid homeostasis. Barrier function of the wound-site was thus compromised. This work demonstrates that microbial pathogens must co-opt host skin lipids to unleash biofilm pathogenicity. Anti-biofilm strategies must not necessarily always target the microbe and targeting host lipids at risk of infection could be productive. This work may be viewed as a first step, laying fundamental mechanistic groundwork, toward a paradigm change in biofilm management.