Global Transcriptomic Analysis During Murine Pneumonia Infection Reveals New Virulence Factors in Acinetobacter baumannii

J Infect Dis. 2021 Apr 23;223(8):1356-1366. doi: 10.1093/infdis/jiaa522.

Abstract

Background: Infections caused by multidrug-resistant pathogens such as Acinetobacter baumannii constitute a major health problem worldwide. In this study we present a global in vivo transcriptomic analysis of A. baumannii isolated from the lungs of mice with pneumonia infection.

Methods: Mice were infected with A. baumannii ATCC 17978 and AbH12O-A2 strains and the total bacterial RNA were analyzed by RNA sequencing. Lists of differentially expressed genes were obtained and 14 of them were selected for gene deletion and further analysis.

Results: Transcriptomic analysis revealed a specific gene expression profile in A. baumannii during lung infection with upregulation of genes involved in iron acquisition and host invasion. Mutant strains lacking feoA, mtnN, yfgC, basB, hisF, oatA, and bfnL showed a significant loss of virulence in murine pneumonia. A decrease in biofilm formation, adherence to human epithelial cells, and growth rate was observed in selected mutants.

Conclusions: This study provides an insight into A. baumannii gene expression profile during murine pneumonia infection. Data revealed that 7 in vivo upregulated genes were involved in virulence and could be considered new therapeutic targets.

Keywords: Acinetobacter baumannii; animal infection models; in vivo transcriptome; murine pneumonia; pathogenesis; virulence factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acinetobacter Infections* / microbiology
  • Acinetobacter baumannii* / genetics
  • Animals
  • Bacterial Adhesion
  • Cells, Cultured
  • Epithelial Cells / microbiology
  • Humans
  • Mice
  • Pneumonia, Bacterial* / microbiology
  • Transcriptome*
  • Virulence Factors* / genetics

Substances

  • Virulence Factors