1 Barcelona Institute for Global Health (ISGlobal) Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.
2 National Institute of Health and Medical Research, U1047, Montpellier University, Nîmes, France.
Microb Drug Resist. 2019 Jun;25(5):752-760. doi: 10.1089/mdr.2018.0182. Epub 2019 Jan 11.
This study analyzed the virulence of several strains expressing different resistance mechanisms using the infection model. Strains susceptible/resistant to carbapenems (presenting class D (OXA-23, OXA-24), class B metallo-β-lactamase (MBL) (NDM-1), penicillin binding protein (PBP) altered and decreased expression of Omp 33-36 kDa) and isogenic strains susceptible/resistant to colistin (presenting loss of lipopolysaccharide (LPS) and A mutations) were included to evaluate the virulence using the infection model. The nematode killing assay, bacterial ingestion in worms, and bacterial lawn avoidance assay were performed with the Fer-15 mutant line. strains generally presented low virulence, showing no difference between carbapenem-resistant strains (expressing class D, MBLs, or altered PBP) and their isogenic susceptible strains. In contrast, the absence of the Omp 33-36 kDa protein in the was associated with a decrease of virulence, and a significant difference was observed between colistin-resistant mutants and their susceptible counterpart when the mechanism of resistance was associated with the loss of LPS but not with its modification. Resistance to carbapenems in associated with the production of OXA-type or NDM-type enzymes does not seem to affect their virulence in the infection model. In contrast, the presence of Omp 33-36 kDa, and high level resistance to colistin related with the loss of LPS, might contribute with the virulence profile in
本研究使用感染模型分析了表达不同耐药机制的几种菌株的毒力。纳入了对碳青霉烯类药物敏感/耐药（表现为 D 类（OXA-23、OXA-24）、B 型金属β-内酰胺酶（MBL）（NDM-1）、青霉素结合蛋白（PBP）改变和 Omp 33-36 kDa 表达降低）和对多黏菌素敏感/耐药的同源菌株（表现为脂多糖（LPS）丢失和 A 突变），以使用感染模型评估毒力。使用 Fer-15 突变株进行线虫杀伤试验、蠕虫中细菌摄取和细菌草坪回避试验。通常情况下，这些菌株的毒力较低，碳青霉烯类耐药菌株（表达 D 类、MBL 或改变的 PBP）与其同源敏感菌株之间没有差异。相比之下，Omp 33-36 kDa 蛋白在中的缺失与毒力下降有关，当耐药机制与 LPS 丢失而非修饰相关时，多黏菌素耐药突变体与其敏感对应体之间存在显著差异。与 OXA 型或 NDM 型酶产生相关的耐碳青霉烯类药物似乎不会影响它们在感染模型中的毒力。相比之下，Omp 33-36 kDa 的存在以及与 LPS 丢失相关的高水平多黏菌素耐药可能有助于其在中的毒力特征。
