Nitric Oxide Signaling inPseudomonas aeruginosaBiofilms Mediates Phosphodiesterase Activity, Decreased Cyclic Di-GMP Levels, and Enhanced Dispersal

Abstract

Bacterial biofilms are highly dynamic communities which display a range of differentiated phenotypes during the course of development. By exchange of cell-cell signals, subpopulations of cells can coordinate their activity and undertake particular metabolic tasks or defense strategies (56). At times, the bacterial community releases single cells that escape from the biofilm and revert to a free-swimming, planktonic mode of growth, leaving behind hollow voids in the biofilm architecture (5, 37, 57). This process, referred to as dispersal, completes the biofilm life cycle and is thought to be important for successful colonization of new surfaces. Although the mechanisms underlying these events remain to be fully elucidated, previous studies of various species, including the opportunistic pathogen Pseudomonas aeruginosa, have revealed that dispersal events correlate with the induction of a specific phenotype that involves cellular motility (37, 42).In P. aeruginosa, biofilm dispersal can be triggered by environmental factors, including nutrient (42, 45) and iron (4, 36) availability, and has recently been linked to the intracellular second messenger cyclic di-GMP (c-di-GMP) (45, 47). Numerous studies revealed that decreased c-di-GMP levels are related to a motile mode of growth and to cell dispersal in eubacteria. In this second messenger system, diguanylate cyclases (DGCs) and specific phosphodiesterases (PDEs) are responsible for the biosynthesis and the degradation of c-di-GMP, respectively. DGCs and PDEs contribute to a genetic network that responds to a broad range of environmental cues and/or cell-cell signals and modulate intracellular levels of c-di-GMP, which has been shown to regulate various cellular functions, including biofilm formation, virulence, and dispersal, in many bacterial species (47,(51)(52)(53). Recently, we identified the gas nitric oxide (NO) as an important factor in the regulation of dispersal in P. aeruginosa biofilms (5). Exogenous addition of nontoxic concentrations of NO, typically in the low nanomolar range, was found to stimulate motility and biofilm dispersal in P. aeruginosa. A role for anaerobic metabolism and NO in biofilm dispersal and survival was further supported by other studies of P. aeruginosa (54, 61), Staphylococcus aureus (44), and various single and multispecies biofilms (6).NO is a water-soluble, hydrophobic free radical that can freely diffuse in biological systems. At high concentrations (micromolar to millimolar range), NO

Sticky Situations: Key Components That Control Bacterial Surface Attachment

“…First described to control extracellular cellulose biosynthesis in Acetobacter xylinum, high c-di-GMP levels are now known to correlate with the motile-sessile transition in several microorganisms (32, 69, 112, 136-138, 142, 152). Modulation of c-di-GMP has furthermore been linked to biofilm dispersion (9,50,112,152), a mechanism used by biofilm bacteria to successfully transition to the planktonic growth state (140). C-di-GMP production and degradation are controlled by diguanylate cyclases (DGCs) and phosphodiesterases (PDEs), respectively, with overexpression of these enzymes generally causing global effects.…”

The role of quorum sensing signalling in EPS production and the assembly of a sludge community into aerobic granules

“…The formation and dispersal of structured bacterial biofilms or aggregates occur in response to a range of environmental cues and signals, such as changes in nutrient concentrations, oxygen, temperature, as well as chemicals and predatory stresses (Bassler et al, 1993;Matz et al, 2004;McDougald et al, 2011;Mitri et al, 2011). In many cases, the signal transduction pathways, the associated changes in gene expression and the involvement of second messenger systems have also begun to be unravelled (Barraud et al, 2009;Petrova and Sauer, 2012). For example, it is now well appreciated that many bacteria rely on a regulatory system based on the production, secretion and response to signalling molecules, termed quorum sensing (QS), as a mechanism to control biofilm development for bacterial populations and this form of control is also postulated to occur within bacterial communities (Williams et al, 2007).…”

Dispersed cells represent a distinct stage in the transition from bacterial biofilm to planktonic lifestyles

“…Bacterial cells can adjust their intracellular c-di-GMP content rapidly to adapt to complex and changing environmental conditions. During exposure to stress, including starvation and nitrosative conditions, bacterial cells can reduce their intracellular c-di-GMP content by activating specific PDEs, resulting in biofilm dispersal [12][13][14] . The active process of dispersing cells is specific and regulated, in contrast to mechanical and passive dispersal, which involves sloughing off biofilm cells.…”