ppGpp signaling plays a critical role in virulence of Acinetobacter baumannii

Virulence. 2021 Dec;12(1):2122-2132. doi: 10.1080/21505594.2021.1961660.

Abstract

Acinetobacter baumannii, a major nosocomial pathogen, survives in diverse hospital environments, and its multidrug resistance is a major concern. The ppGpp-dependent stringent response mediates the reprogramming of genes with diverse functions in several bacteria. We investigated whether ppGpp is involved in A. baumannii's pathogenesis by examining biofilm formation, surface motility, adhesion, invasion, and mouse infection studies. Transcriptome analysis of early stationary phase cultures revealed 498 differentially-expressed genes (≥ 2-fold change) in a ppGpp-deficient A. baumannii strain; 220 and 278 genes were up and downregulated, respectively. Csu operon expression, important in pilus biosynthesis during early biofilm formation, was significantly reduced in the ppGpp-deficient strain. Our findings suggest that ppGpp signaling influences A. baumannii biofilm formation, surface motility, adherence, and virulence. We showed the association between ppGpp and pathogenicity in A. baumannii for the first time; ppGpp may be a novel antivirulence target in A. baumannii.

Keywords: Acinetobacter baumannii; biofilm; ppGpp; transcriptome; virulence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acinetobacter baumannii* / genetics
  • Acinetobacter baumannii* / pathogenicity
  • Animals
  • Biofilms
  • Fimbriae, Bacterial
  • Gene Expression Regulation, Bacterial
  • Guanosine Tetraphosphate / metabolism*
  • Mice
  • Operon
  • Transcriptome
  • Virulence*

Substances

  • Guanosine Tetraphosphate

Grants and funding

This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education [2016R1D1A1B01008960].