Virulence role of the outer membrane protein CarO in carbapenem-resistant Acinetobacter baumannii

Virulence

Carlos S. Casimiro-Soriguer¹  Antonio J. Pérez-Pulido¹  Rocío Álvarez-Marín²  Gema Labrador-Herrera²  María Eugenia Pachón-Ibáñez²  Tania Cebrero-Cangueiro³  Jerónimo Pachón⁴  Alejandro M. Viale⁵  Jorgelina Morán-Barrio⁵ 

[1] Andalusian Centre for Developmental Biology (CABD, UPO-CSIC-JA), Faculty of Experimental Sciences (Genetics Area), Pablo de Olavide University, Seville, Spai;Clinical Unit of Infectious Diseases, Microbiology, and Preventive Medicine, University Hospital Virgen del Rocío, Seville, Spai;Institute of Biomedicine of Seville (IBiS), University of Seville/CSIC/University Hospital Virgen del Rocío, Seville, Spai;Clinical Unit of Infectious Diseases, Microbiology, and Preventive Medicine, University Hospital Virgen del Rocío, Seville, Spai;Institute of Biomedicine of Seville (IBiS), University of Seville/CSIC/University Hospital Virgen del Rocío, Seville, Spai;Department of Medicine, University of Seville, Seville, Spai;Institute of Biomedicine of Seville (IBiS), University of Seville/CSIC/University Hospital Virgen del Rocío, Seville, Spai;Department of Medicine, University of Seville, Seville, Spai;Instituto de Biología Molecular y Celular de Rosario (IBR), Departamento de Microbiología, Facultad de Ciencias Bioquímicas y Farmacéuticas, CONICET, Universidad Nacional de Rosario (UNR), Rosario, Argentin;

关键词: Acinetobacter baumannii;    bloodstream infections;    carbapenem-resistance;    whole-genome sequencing;    virulence factor;    CarO;   

DOI  :  10.1080/21505594.2020.1855912

来源: Taylor & Francis

【 摘 要 】

Novel approaches to treat carbapenem-resistant Acinetobacter baumannii (CRAB) infections are urgently needed and anti-virulence drugs represent promising alternatives, but our knowledge on potential targets is scarce. We searched for potential A. baumannii virulence factors by whole-genome sequencing-based comparisons of CRAB clinical isolates causing bloodstream infections secondary to ventilator-associated pneumonia from demographics and clinically homogeneous patients, who received optimal treatment but with different clinical outcomes. Thus, the carO gene was interrupted in CRAB isolates from surviving patients, while it was intact in isolates from non-surviving patients, and proteomic/immunoblot techniques corroborated it. When the virulence role of A. baumannii CarO was analyzed in model systems, isogenic ΔcarO mutants and a CRAB clinical isolate with truncated CarO, showed lower ability to adhere and invade A549 cells and in vivo virulence. This unnoticed virulence role for CarO postulate this A. baumannii outer membrane protein as a potential target for new therapies against CRAB infections.

【 授权许可】

CC BY