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Second messenger signalling governs Escherichia coli biofilm induction upon ribosomal stress
Author(s) -
Boehm Alex,
Steiner Samuel,
Zaehringer Franziska,
Casanova Alain,
Hamburger Fabienne,
Ritz Daniel,
Keck Wolfgang,
Ackermann Martin,
Schirmer Tilman,
Jenal Urs
Publication year - 2009
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/j.1365-2958.2009.06739.x
Subject(s) - biofilm , biology , ribosome , stringent response , second messenger system , escherichia coli , bacterial adhesin , protein biosynthesis , microbiology and biotechnology , ribosomal protein , biochemistry , bacteria , signal transduction , rna , gene , genetics
Summary Biofilms are communities of surface‐attached, matrix‐embedded microbial cells that can resist antimicrobial chemotherapy and contribute to persistent infections. Using an Escherichia coli biofilm model we found that exposure of bacteria to subinhibitory concentrations of ribosome‐targeting antibiotics leads to strong biofilm induction. We present evidence that this effect is elicited by the ribosome in response to translational stress. Biofilm induction involves upregulation of the polysaccharide adhesin poly‐β‐1,6‐N‐acetyl‐glucosamine (poly‐GlcNAc) and two components of the poly‐GlcNAc biosynthesis machinery, PgaA and PgaD. Poly‐GlcNAc control depends on the bacterial signalling molecules guanosine‐bis 3′, 5′(diphosphate) (ppGpp) and bis‐(3′‐5′)‐cyclic di‐GMP (c‐di‐GMP). Treatment with translation inhibitors causes a ppGpp hydrolase (SpoT)‐mediated reduction of ppGpp levels, resulting in specific derepression of PgaA. Maximal induction of PgaD and poly‐GlcNAc synthesis requires the production of c‐di‐GMP by the dedicated diguanylate cyclase YdeH. Our results identify a novel regulatory mechanism that relies on ppGpp signalling to relay information about ribosomal performance to the Pga machinery, thereby inducing adhesin production and biofilm formation. Based on the important synergistic roles of ppGpp and c‐di‐GMP in this process, we suggest that interference with bacterial second messenger signalling might represent an effective means for biofilm control during chronic infections.