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Virulence role of the outer membrane protein CarO in carbapenem-resistant Acinetobacter baumannii
Gema Labrador-Herrera1,2, Antonio J Pérez-Pulido3, Rocío Álvarez-Marín1,2
1Clinical Unit of Infectious Diseases, Microbiology, and Preventive Medicine, University Hospital Virgen del Rocío , Seville, Spain.
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.
Insights
Carbapenem-resistant Acinetobacter baumannii (CRAB) infections require new treatments. The CarO protein, previously unnoticed, may be a target for anti-virulence drugs against CRAB.
Area of Science:
- Microbiology
- Infectious Diseases
- Genomics
Background:
- Novel therapies are crucial for treating carbapenem-resistant Acinetobacter baumannii (CRAB) infections.
- Anti-virulence drugs offer a promising alternative to traditional antibiotics, but target identification remains limited.
Purpose of the Study:
- To identify potential virulence factors of CRAB by comparing clinical isolates from patients with different outcomes.
- To investigate the role of the CarO protein in A. baumannii virulence.
Main Methods:
- Whole-genome sequencing of CRAB clinical isolates from patients with ventilator-associated pneumonia.
- Proteomic and immunoblot analyses to corroborate gene findings.
- In vitro (cell adhesion and invasion assays) and in vivo virulence studies of A. baumannii mutants.
Main Results:
- The carO gene was found to be interrupted in CRAB isolates from surviving patients, but intact in isolates from non-surviving patients.
- Isogenic ΔcarO mutants and CRAB isolates with truncated CarO exhibited reduced adherence to and invasion of A549 cells.
- A. baumannii lacking functional CarO showed decreased in vivo virulence.
Conclusions:
- The outer membrane protein CarO plays a previously unrecognized role in A. baumannii virulence.
- CarO is a potential therapeutic target for developing novel anti-virulence strategies against CRAB infections.
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