UMR-MD-1, Facultés de Médecine et de Pharmacie, IFR 88, Université de la Méditerranée, Marseille, France.
Clin Microbiol Infect. 2012 Jun;18(6):539-45. doi: 10.1111/j.1469-0691.2011.03607.x. Epub 2011 Aug 29.
Imipenem-susceptible E. aerogenes isolates exhibiting extended spectrum β-lactamases, target mutations and a basal efflux expression, were identified in five patients. After imipenem treatment, imipenem-intermediate susceptible (IMI-I) or resistant (IMI-R) isolates emerged in these patients. Alteration in porin synthesis and increase in efflux expression were observed in the IMI-I isolates whereas complete loss of the porins, LPS alteration and efflux overexpression were observed in the IMI-R isolates. Bacterial virulence of the strains was investigated by the Caenorhabditis elegans model. The IMI-R isolates were shown to be significantly less virulent than the IMI-susceptible or IMI-I isolates. The pleiotropic membrane alteration and its associated fitness burden exhibited by E. aerogenes isolates influence their antibiotic resistance and their virulence behaviour. These findings highlight the balance between the low permeability-related resistance and virulence and their relationships with the treatment of resistant pathogens.
在五名患者中发现了对亚胺培南敏感的产气肠杆菌分离株,这些分离株表现出广谱β-内酰胺酶、靶突变和基础外排表达。在这些患者中,在接受亚胺培南治疗后,出现了对亚胺培南中介(IMI-I)或耐药(IMI-R)的分离株。在 IMI-I 分离株中观察到孔蛋白合成的改变和外排表达的增加,而在 IMI-R 分离株中观察到孔蛋白完全缺失、LPS 改变和外排过度表达。通过秀丽隐杆线虫模型研究了菌株的细菌毒力。结果表明,IMI-R 分离株的毒力明显低于 IMI-敏感或 IMI-I 分离株。产气肠杆菌分离株表现出的多效性膜改变及其相关的适应性负担,影响了它们的抗生素耐药性和毒力行为。这些发现强调了低渗透性相关耐药性和毒力之间的平衡,以及它们与耐药病原体治疗的关系。