Research ArticleMicrobiology

Constitutive production of c-di-GMP is associated with mutations in a variant of Pseudomonas aeruginosa with altered membrane composition

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Sci. Signal.  14 Apr 2015:
Vol. 8, Issue 372, pp. ra36
DOI: 10.1126/scisignal.2005943

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Making bacteria sticky

When free-swimming bacteria encounter a surface, such as the inner lining of a catheter or an airway in a patient with cystic fibrosis (CF), they aggregate to form a biofilm, which is an encapsulated, multicellular structure that has increased resistance to environmental conditions and antimicrobial compounds. Blanka et al. sequenced a small colony variant of the opportunistic pathogen Pseudomonas aeruginosa, isolated from the lung of a patient with CF, and found a mutation in a gene cluster that encodes a multisubunit enzyme responsible for fatty acid biosynthesis, which altered the composition of the P. aeruginosa plasma membrane. The altered membrane composition resulted in the constitutive production of the second messenger c-di-GMP, which promotes biofilm formation. Understanding the opportunistic adaptations that promote biofilm formation may help in designing therapies to treat biofilm-associated infections.

Abstract

Most bacteria can form multicellular communities called biofilms on biotic and abiotic surfaces. This multicellular response to surface contact correlates with an increased resistance to various adverse environmental conditions, including those encountered during infections of the human host and exposure to antimicrobial compounds. Biofilm formation occurs when freely swimming (planktonic) cells encounter a surface, which stimulates the chemosensory-like, surface-sensing system Wsp and leads to generation of the intracellular second messenger 3′,5′-cyclic-di-guanosine monophosphate (c-di-GMP). We identified adaptive mutations in a clinical small colony variant (SCV) of Pseudomonas aeruginosa and correlated their presence with self-aggregating growth behavior and an enhanced capacity to form biofilms. We present evidence that a point mutation in the 5′ untranslated region of the accBC gene cluster, which encodes components of an enzyme responsible for fatty acid biosynthesis, was responsible for a stabilized mRNA structure that resulted in reduced translational efficiency and an increase in the proportion of short-chain fatty acids in the plasma membrane. We propose a model in which these changes in P. aeruginosa serve as a signal for the Wsp system to constitutively produce increased amounts of c-di-GMP and thus play a role in the regulation of adhesion-stimulated bacterial responses.

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