Bacterial efflux pump OMPs as vaccine candidates against multidrug-resistant Gram-negative bacteria

Author:

Silva Thaynara O12,Bulla Ana Carolina S3,Teixeira Bárbara A1,Gomes Vinnicius Machado Schelk4,Raposo Thiago1,Barbosa Luiza S12,da Silva Manuela Leal34,Moreira Lilian O2,Olsen Priscilla C1ORCID

Affiliation:

1. 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

2. 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

3. Programa de Pós-graduação em Biologia Computacional e Sistemas, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Avenida Brasil 4365, Manguinhos , Rio de Janeiro, RJ, 21040-900 , Brazil

4. Programa de Pós-graduação Multicêntrico em Ciências Fisiológicas, Instituto de Biodiversidade e Sustentabilidade NUPEM, Universidade Federal do Rio de Janeiro, Avenida São José do Barreto, 764. Centro , Macaé, RJ, 27965-045 , Brazil

Abstract

Abstract 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.

Funder

Pew Charitable Trusts Funds

Brazilian Council for Scientific and Technological Development

CNPq

Fundação Carlos Chagas de Amparo à Pesquisa do Estado do Rio de Janeiro

FAPERJ

CAPES

Publisher

Oxford University Press (OUP)

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