Cho Youn Hee, Renouf Michael J, Omotoso Oluwafikemi, McPhee Joseph B
Department of Chemistry and Biology, Toronto Metropolitan University (Formerly Ryerson University), 350 Victoria St., Toronto, ON M5B 2K3, Canada.
FEMS Microbiol Lett. 2022 Oct 26;369(1). doi: 10.1093/femsle/fnac098.
Adherent-invasive Escherichia coli (AIEC) are isolated from inflammatory bowel disease (IBD) patients at a higher rate than from control patients. Using a collection of E. coli strains collected from Crohn's disease (CD), ulcerative colitis (UC), or non-IBD control patients, antibiotic and resistance to the antimicrobial peptides HBD-3 and LL-37 was assessed. Carriage of bacterial-encoded omptin protease genes was assessed by PCR and omptin protease activity was measured using a whole-cell based fluorescence assay. Elevated resistance to antibiotics and host defense peptides in IBD-associated AIEC were observed. IBD-associated strains showed increased (but statistically non-significant) antibiotic resistance. CD-associated strains showed greater (but statistically non-significant) resistance to HBD3-mediated killing while UC-associated strains showed statistically greater resistance to LL-37 mediated killing. High-level resistance to LL-37 was associated with carriage of omptin protease genes and with increased omptin protease activity. Antimicrobial host defense peptide resistance may be an adaptive feature of AIEC leading to enhanced pathogenesis during the initiation or progression of IBD.
与非炎症性肠病（IBD）患者相比，粘附侵袭性大肠杆菌（AIEC）在炎症性肠病（IBD）患者中的分离率更高。使用从克罗恩病（CD）、溃疡性结肠炎（UC）或非IBD对照患者中收集的大肠杆菌菌株集合，评估了抗生素以及对抗菌肽HBD-3和LL-37的耐药性。通过PCR评估细菌编码的omptin蛋白酶基因的携带情况，并使用基于全细胞的荧光测定法测量omptin蛋白酶活性。观察到IBD相关AIEC对抗生素和宿主防御肽的耐药性升高。IBD相关菌株显示出抗生素耐药性增加（但在统计学上无显著差异）。CD相关菌株对HBD3介导的杀伤表现出更高（但在统计学上无显著差异）的耐药性，而UC相关菌株对LL-37介导的杀伤表现出统计学上更高的耐药性。对LL-37的高水平耐药性与omptin蛋白酶基因的携带以及omptin蛋白酶活性增加有关。抗菌宿主防御肽耐药性可能是AIEC的一种适应性特征，导致IBD发生或进展期间发病机制增强。
