Assessing the Role of Cold-Shock Protein C: a Novel Regulator of Acinetobacter baumannii Biofilm Formation and Virulence

Brooke R. Tomlinson, Grant A. Denham, Nathanial J. Torres, Robert S. Brzozowski, Jessie L. Allen, Jessica K. Jackson, Prahathees J. Eswara, Lindsey N. Shaw

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Acinetobacter baumannii is a formidable opportunistic pathogen that is notoriously difficult to eradicate from hospital settings. This resilience is often attributed to a proclivity for biofilm formation, which facilitates a higher tolerance toward external stress, desiccation, and antimicrobials. Despite this, little is known regarding the mechanisms orchestrating A. baumannii biofilm formation. Here, we performed RNA sequencing (RNA-seq) on biofilm and planktonic populations for the multidrugresistant isolate AB5075 and identified 438 genes with altered expression. To assess the potential role of genes upregulated within biofilms, we tested the biofilm-forming capacity of their respective mutants from an A. baumannii transposon library. In so doing, we uncovered 24 genes whose disruption led to reduced biofilm formation. One such element, cold shock protein C (cspC), had a highly mucoid colony phenotype, enhanced tolerance to polysaccharide degradation, altered antibiotic tolerance, and diminished adherence to abiotic surfaces. RNA-seq of the cspC mutant revealed 201 genes with altered expression, including the downregulation of pili and fimbria genes and the upregulation of multidrug efflux pumps. Using transcriptional arrest assays, it appears that CspC mediates its effects, at least in part, through RNA chaperone activity, influencing the half-life of several important transcripts. Finally, we show that CspC is required for survival during challenge by the human immune system and is key for A. baumannii dissemination and/or colonization during systemic infection. Collectively, our work identifies a cadre of new biofilm-associated genes within A. baumannii and provides unique insight into the global regulatory network of this emerging human pathogen.

Original languageEnglish
JournalInfection and Immunity
Volume90
Issue number10
DOIs
StatePublished - Oct 2022

Keywords

  • A. baumannii
  • Csp
  • biofilms

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