# Nutrient Sensing and Biofilm Modulation: The Example of L-arginine in _Pseudomonas_
## 6 Concluding Remarks  
Bacterial biofilms represent a biomedical and industrial issue, being related to chronic and nosocomial infections, antibiotic resistance, pipeline deterioration and goods contamination/degradation [94]. Although diverse, species belonging to _Pseudomonas_ are relevant in all such issues due to their extraordinary metabolic versatility which confers high adaptability to these bacteria [95]. Nevertheless, the _Pseudomonas_ biofilm may represent a biocontrol tool to protect against other microorganisms, including pathogens [96]. As robust, self-immobilised and self-regenerating biocatalysts, _Pseudomonas_ biofilm-based bioreactors can be applied for waste treatment in biodegradation and bioremediation processes or used for fermentative biotransformation [97; 98]. Particularly, _P. putida_ is acknowledged as a possible cell factory through an engineering catalytic biofilm [99].  
The environmental setting is crucial to sustain biofilm maintenance and dispersion, in particular nutrient availability [24]. In the _P. aeruginosa_ biofilm, dispersal is inducible by nutrients, especially by increasing the amount of carbon sources [100]. In general, resource limitation and hostile environment promote biofilm formation in this bacterium [101].  
It is now accepted that natural anti-biofilm agents, including metabolites, sensitie _P. aeruginosa_ to antibiotics, and their use in combination with more traditional drugs is promising [102].  
Among the most promising nutrients to tackle threatening human biofilms, L-arginine is one of the most versatile, being known to affect biofilm homeostasis and, simultaneously, augment the host's defense by sustaining NO production.  
Despite the large repertoire of literature data, the molecular mechanisms linking L-arginine perception and utilization to c-di-GMP and biofilms are starting to emerge [44; 63; 102]. Identifying the sensory domains of chemoreceptors specific for L-arginine and the regulatory elements involved in the connection between the amino acid and second messenger pools will provide new insights in biofilm adaptation strategies and the metabolic state of bacteria within a biofilm.  
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.  
Considering all this, the future dissection of the molecular mechanisms controlling the L-arginine-dependent metabolic reprogramming in _Pseudomonas_ will be helpful for both biomedical and biotechnological applications.  
[PERSON] and [PERSON] designed the outline and wrote the paper; [PERSON] and [PERSON] contributed to writing and supported the bibliographic search and bibliography layout; [PERSON]. ([PERSON]) projected and made the Figure; [PERSON]. ([PERSON]) and F.C. supported for host-pathogen interaction topic. All authors have read and agreed to the published version of the manuscript.  
The authors would like to acknowledge the Sapienza University of Rome (RM120172A7 AD98 EB to S.R. and AR12117A63 EE6037 to C.S.R.) for financial support; the support from grant PID2019-109372 GB-I00 funded by MCIN/ AEI/10.13039/501100011033 and \"ERDF. A way of making Europe\" by the European Union are also acknowledged. [PERSON] is the recipient of a postdoctoral fellowship from Fundacion Alfonso Martin Escudero.  
The authors declare no conflict of interest.