Exploring the Links between Nucleotide Signaling and Quorum Sensing Pathways in Regulating Bacterial Virulence

Abstract

The survival of all organisms depends on implementation of appropriate phenotypic responses upon perception of relevant environmental stimuli. Sensory inputs are propagated via interconnected biochemical and/or electrical cascades mediated by diverse signaling molecules, including gases, metal cations, lipids, peptides, and nucleotides. These networks often comprise second messenger signaling systems in which a ligand (the primary messenger) binds an extracellular receptor, thereby altering the intracellular concentration of a second messenger molecule which ultimately modulates gene expression through interaction with various effectors. The identification of intersections of these signaling pathways, such as nucleotide second messengers and quorum sensing, provides new insights into the mechanisms by which bacteria use multiple inputs to regulate cellular metabolism and phenotypes. Further investigations of the overlap between bacterial signaling pathways may yield new targets and methods to control bacterial behavior, such as biofilm formation and virulence.

Pseudomonas aeruginosa Presents Multiple Vital Changes in Its Proteome in the Presence of 3-Hydroxyphenylacetic Acid, a Promising Antimicrobial Agent

“… 31 Accordingly, DNA binding transcriptional regulator NtrC ( ntrC ), which has a role in nitrogen utilization, was also undetected, which might show the reduction in nitrogen assimilation in bacteria. The phosphate regulon transcriptional regulatory protein PhoB ( phoB ), which is the major transcription factor that functions in the phosphate limitation of the bacteria, 32 was newly detected ( Table 3 ). Since rpoN , ntrC , and phoB show strong interactions ( Figure 4 B), the treatment of P. aeruginosa with 3-HPAA might cause the bacteria to experience nitrogen and phosphate starvation and, eventually, bacterial growth inhibition.…”

Biofilm matrix proteome of clinical strain of P. aeruginosa

“…Digestion and consumption of polymeric extracellular nucleic acids requires at least extracellular nucleases. Also, nucleosides act as signal molecules and involved in regulation of bacterial community inside biofilm [50], so targeting of proteins involved in these processes is theoretically possible, but at the present time is not clear.…”

Advances in Pulmonary Drug Delivery Targeting Microbial Biofilms in Respiratory Diseases

“…Another approach to prevent biofilm formation focuses on disrupting the signaling pathways of bacterial cell that coordinate with the genes responsible for biofilm development. For instance, the (p)ppGpp, cyclic-di-GMP inhibitors and quorum sensing (QS) signaling have shown positive results in the prevention of biofilm formation and could also potentially lead to novel therapeutic strategies [23].…”