Zhao Chong-Yi, Li Xiao, Zhao Ting, Liu Ying, Xia Xue-Shan, Wu Xiao-Mei
Department of Gynecology, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, China.
Medical School, Kunming University of Science and Technology, Kunming, China.
Front Microbiol. 2025 Mar 5;15:1516808. doi: 10.3389/fmicb.2024.1516808. eCollection 2024.
The aim of this study is to examine the functional role and resistance mechanisms of the () peptidoglycan transpeptidase gene, , in resistance to melittin.
The resistance of strains with either knockout or overexpression of the gene to melittin was initially assessed. The differences in melittin absorption between these two strains were evaluated following depletion and heterologous expression of the gene. Subsequently, peptidoglycan was extracted from the strains to determine its capacity to adsorb melittin. Finally, the morphological changes in different strains induced by melittin exposure were examined under scanning electron microscopy. These analyses served to validate the role of peptidoglycan transpeptidase in melittin resistance and to hypothesize its potential resistance mechanism.
The results clearly indicated a direct correlation between the degree of peptidoglycan cross-linking in and its enhanced resistance to melittin. Specifically, we found that increased cross-linking of peptidoglycan led to a thickening of the bacterial cell wall and a reduction in pore size. These structural changes potentially decrease the damage to the cell wall caused by melittin, as the thicker cell wall and smaller pores reduce the ability of melittin to penetrate and access the interior of bacterial cells. This mechanism effectively limits the contact between melittin and bacterial components, minimizing its destructive effects, and thereby conferring resistance to melittin in the bacteria.
This study is the first to elucidate the role of peptidoglycan in the cell wall of in the context of antimicrobial peptide resistance. Novel ideas have been proposed for the development of antibacterial drugs targeting the peptidoglycan of Gram-negative bacteria.
本研究旨在探讨（）肽聚糖转肽酶基因在抵抗蜂毒素中的功能作用及耐药机制。
首先评估基因敲除或过表达的菌株对蜂毒素的耐药性。在基因缺失和异源表达后，评估这两种菌株在蜂毒素吸收方面的差异。随后，从菌株中提取肽聚糖以确定其吸附蜂毒素的能力。最后，在扫描电子显微镜下检查蜂毒素暴露诱导的不同菌株的形态变化。这些分析旨在验证肽聚糖转肽酶在蜂毒素耐药性中的作用，并推测其潜在的耐药机制。
结果清楚地表明中肽聚糖交联程度与其对蜂毒素的增强耐药性之间存在直接相关性。具体而言，我们发现肽聚糖交联增加导致细菌细胞壁增厚和孔径减小。这些结构变化可能会减少蜂毒素对细胞壁的损伤，因为较厚的细胞壁和较小的孔减少了蜂毒素穿透和进入细菌细胞内部的能力。这种机制有效地限制了蜂毒素与细菌成分之间的接触，将其破坏作用降至最低，从而赋予细菌对蜂毒素的抗性。
本研究首次阐明了肽聚糖在抗微生物肽耐药性背景下在细胞壁中的作用。针对革兰氏阴性菌肽聚糖开发抗菌药物提出了新的思路。
