To increase survival and transmission, the pathogen Pseudomonas aeruginosa forms biofilms, or adherent clumps of cells encased in a sticky matrix, in response to environmental stresses. One environmental stressor is hypothermia, such as its transfer from the human host to hospital room temperature, where P. aeruginosa is particularly dangerous to frail patients.
Janice Haney Carr, Centers for Disease Control and Prevention, via Wikimedia Commons
Scanning electron micrograph of Pseudomonas aeruginosa.
Mechanistically, the secondary messenger diguanosine 3′,5′-monophosphate, or c-di-GMP, is increased to promote biofilm formation. While P. aeruginosa expresses several enzymes that regulate c-di-GMP levels, how each enzyme responds to distinct environmental signals remains unclear.
Recently He studies Published in Journal of Biological ChemistryYanran Li from the University of Hong Kong and a team of researchers in China used a mutation screening library to identify SiaD, a cyclic diguanylate enzyme that generates c-di-GMP, as responsible for stimulating biofilm formation in P. aeruginosa during low temperatures.
Measured using a membrane-sensitive probe, lipidomics and RNA sequencing, the researchers found that when the temperature changed from 37°C to 25°C, the P. aeruginosa membrane became disordered, increasing fluidity and curvature. The SiaABCD signal transduction module senses these membrane disturbances and responds to them by promoting biofilm formation. Specifically, upon low temperature, membrane changes activate SiaABCD through the inner membrane phosphorylation SiaA. SiaA dephosphorylates SiaC, a regulator of c-di-GMP, and synthesizes SiaD. SiaD elevates c-di-GMP levels, leading to matrix-forming polysaccharide production and eventual biofilm formation. The authors suggest that blocking signaling through SiaA could be a potential strategy to prevent P. aeruginosa biofilm formation and transmission.
