Laboratório de Estudos em Imunologia, Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho 373, Bloco A 2º Andar sala 05, Cidade Universitária, Ilha do Fundão, Rio de Janeiro, RJ, 21941-902, Brazil.
Laboratório de Bacteriologia e Imunologia Clínica, Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho 373, Bloco A 2º Andar sala 07, Cidade Universitária, Ilha do Fundão, Rio de Janeiro, RJ, 21941-902, Brazil.
J Leukoc Biol. 2024 Nov 27;116(6):1237-1253. doi: 10.1093/jleuko/qiae154.
The emergence and propagation of bacteria resistant to antimicrobial drugs is a serious public health threat worldwide. The current antibacterial arsenal is becoming obsolete, and the pace of drug development is decreasing, highlighting the importance of investment in alternative approaches to treat or prevent infections caused by antimicrobial-resistant bacteria. A significant mechanism of antimicrobial resistance employed by Gram-negative bacteria is the overexpression of efflux pumps that can extrude several compounds from the bacteria, including antimicrobials. The overexpression of efflux pump proteins has been detected in several multidrug-resistant Gram-negative bacteria, drawing attention to these proteins as potential targets against these pathogens. This review will focus on the role of outer membrane proteins from efflux pumps as potential vaccine candidates against clinically relevant multidrug-resistant Gram-negative bacteria, discussing advantages and pitfalls. Additionally, we will explore the relevance of efflux pump outer membrane protein diversity and the possible impact of vaccination on microbiota.
细菌对抗菌药物的耐药性的出现和传播是全球范围内一个严重的公共卫生威胁。目前的抗菌药物库正在逐渐失效,药物开发的速度也在下降,这凸显了投资替代方法来治疗或预防由抗微生物耐药细菌引起的感染的重要性。革兰氏阴性菌采用的一种重要的抗菌药物耐药机制是过度表达外排泵,这些外排泵可以将几种化合物从细菌中排出,包括抗菌药物。在几种多药耐药革兰氏阴性菌中已经检测到外排泵蛋白的过度表达,这使得这些蛋白成为针对这些病原体的潜在靶标。这篇综述将重点介绍外排泵的外膜蛋白作为针对临床相关多药耐药革兰氏阴性菌的潜在疫苗候选物的作用,讨论其优缺点。此外,我们还将探讨外排泵外膜蛋白多样性的相关性以及疫苗接种对微生物组的可能影响。