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

Virulence. 2020 Dec;11(1):1727-1737. doi: 10.1080/21505594.2020.1855912.

Abstract

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.

Keywords: Acinetobacter baumannii; CarO; bloodstream infections; carbapenem-resistance; virulence factor; whole-genome sequencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Acinetobacter Infections / blood
  • Acinetobacter Infections / microbiology*
  • Acinetobacter baumannii / drug effects
  • Acinetobacter baumannii / genetics*
  • Acinetobacter baumannii / pathogenicity*
  • Adult
  • Aged
  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Bacterial Adhesion
  • Bacterial Outer Membrane Proteins / genetics*
  • Bacterial Outer Membrane Proteins / metabolism*
  • Carbapenems / pharmacology*
  • Drug Resistance, Multiple, Bacterial / genetics*
  • Female
  • Genome, Bacterial
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microbial Sensitivity Tests
  • Middle Aged
  • Porins / genetics*
  • Porins / metabolism*
  • Proteomics
  • Virulence
  • Virulence Factors / genetics
  • Whole Genome Sequencing

Substances

  • Anti-Bacterial Agents
  • Bacterial Outer Membrane Proteins
  • CarO protein, Acinetobacter baumannii
  • Carbapenems
  • Porins
  • Virulence Factors

Grants and funding

This work was supported by the Instituto de Salud Carlos III, Proyectos de Investigación en Salud under grant [PI12/0255]; Plan Nacional de I+D+i 2013‐2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades under grant [BFU2016-77297-P]; Plan Nacional de I+D+i 2013‐2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases under grant [REIPI RD16/0016/0009] ‐ co‐financed by European Development Regional Fund “A way to achieve Europe,” Operative program Intelligent Growth 2014‐2020; and Agencia Nacional de Promoción Científica y Tecnológica, ANPCyT, Argentina, under grants [PICT-2015-1072 and PICT-2017-3536]. G.L.H. was supported by the program i-PFIS (Doctorados IIS-Empresa en Ciencias y Tecnologías de la Salud), Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades under grant [IFI15/00128]. T.C.C. is supported by the V Plan Propio of the University of Seville with a postdoctoral contract. M.E.P.I. is a postdoctoral researcher belonging to the program “Nicolás Monardes” (C1-0038-2019), Servicio Andaluz de Salud, Junta de Andalucía, Spain. This study has previously been presented in part at the 11th International Symposium on the Biology of Acinetobacter as oral communication (September 2017; Seville, Spain; abstract O6-1), at the 29th European Congress of Clinical Microbiology & Infectious Diseases as poster (April 2019; Amsterdam, Netherlands; abstract P0916), and at the 12th International Symposium on the Biology of Acinetobacter as oral communication (September 2019; Frankfurt, Germany; abstract O2-2).