Loss of CsrA in Acinetobacter baumannii leads to lethal dysregulation of alanine metabolism

Abstract

Significance In the pathogen Acinetobacter baumannii, the posttranscriptional regulator CsrA is required for growth under certain environmental conditions, including rich growth media and infection-relevant conditions like human serum. However, CsrA is dispensable for A. baumannii grown under nutrient limited conditions, such as a minimal medium containing a single carbon source. Using classical genetic approaches to explore this conditional essentiality, we found that CsrA and Lrp, a global transcription regulator, coordinate expression of several genes involved with D-alanine metabolism. Consistent with D-alanine’s importance to peptidoglycan biosynthesis, csrA mutants exhibit impaired cell envelope integrity. Our findings provide a potential mechanism for the essentiality of CsrA in A. baumannii and further highlight how global regulatory networks intersect to promote fitness under changing environmental conditions.