Nutrient Sensing and Biofilm Modulation: The Example of L-arginine in Pseudomonas

Abstract

Bacterial biofilm represents a multicellular community embedded within an extracellular matrix attached to a surface. This lifestyle confers to bacterial cells protection against hostile environments, such as antibiotic treatment and host immune response in case of infections. The Pseudomonas genus is characterised by species producing strong biofilms difficult to be eradicated and by an extraordinary metabolic versatility which may support energy and carbon/nitrogen assimilation under multiple environmental conditions. Nutrient availability can be perceived by a Pseudomonas biofilm which, in turn, readapts its metabolism to finally tune its own formation and dispersion. A growing number of papers is now focusing on the mechanism of nutrient perception as a possible strategy to weaken the biofilm barrier by environmental cues. One of the most important nutrients is amino acid L-arginine, a crucial metabolite sustaining bacterial growth both as a carbon and a nitrogen source. Under low-oxygen conditions, L-arginine may also serve for ATP production, thus allowing bacteria to survive in anaerobic environments. L-arginine has been associated with biofilms, virulence, and antibiotic resistance. L-arginine is also a key precursor of regulatory molecules such as polyamines, whose involvement in biofilm homeostasis is reported. Given the biomedical and biotechnological relevance of biofilm control, the state of the art on the effects mediated by the L-arginine nutrient on biofilm modulation is presented, with a special focus on the Pseudomonas biofilm. Possible biotechnological and biomedical applications are also discussed.

Keywords: ArgR; Pseudomonas; RmcA; arginine; biofilm; c-di-GMP; metabolism; nutrients.

Figure 1

L-Arginine metabolism in Pseudomonas aeruginosa in a metro-style map. Nodes represent the most relevant metabolite(s) while different colors represent different metabolic categories. Each route represents the metabolic pathway named in the Figure with the same color, linking different nodes. The color code used for the nodes: (i) magenta and light navy nodes for C and N source metabolites, respectively; (ii) green for energy production; (iii) rust orange for other N metabolites. 2NHCO℗: carbamoyl phosphate.

Figure 2

Simplified model of the regulatory network connecting L-arginine metabolism, c-di-GMP signaling and biofilm formation in P. putida KT2440. In the presence of arginine, ArgR positively controls arginine transport and negatively controls de novo arginine biosynthesis; intracellular arginine indirectly influences the c-di-GMP levels (and, therefore, biofilm formation) and, in turn, c-di-GMP modulates the expression of argR, thus establishing a feedback loop [63].

Figure 3

Simplified model of the P. aeruginosa RmcA activation in response to environmental stimuli such as arginine (on the left), which activates the phosphodiesterase activity [64], or electron availability (on the right), whose accumulation leads to reduced c-di-GMP hydrolysis [67]. The question marks indicate missing mechanistic details.