Can Biofilm Be Reversed Through Quorum Sensing in Pseudomonas aeruginosa?

Abstract

<i>Pseudomonas aeruginosa</i> is a Gram-negative bacterium causing diseases in plants, animals, and humans, and its drug resistance is a major concern in medical care. Biofilms play an important role in <i>P. aeruginosa</i> drug resistance. Three factors are most important to induce biofilm: quorum sensing (QS), bis-(3'-5')-cyclic diguanosine monophosphate (c-di-GMP), and small RNAs (sRNAs). <i>P. aeruginosa</i> has its own specific QS system (PQS) besides two common QS systems, LasI-LasR and RhlI-RhlR, in bacteria. PQS is interesting not only because there is a negative regulation from RhlR to <i>pqsR</i> but also because the null mutation in PQS leads to a reduced biofilm formation. Furthermore, <i>P. aeruginosa</i> dispersed cells have physiological features that are distinct between the planktonic cells and biofilm cells. In response to a low concentration of c-di-GMP, <i>P. aeruginosa</i> cells can disperse from the biofilms to become planktonic cells. These raise an interesting hypothesis of whether biofilm can be reversed through the QS mechanism in <i>P. aeruginosa</i>. Although a single factor is certainly not sufficient to prevent the biofilm formation, it necessarily explores such possibility. In this hypothesis, the literature is analyzed to determine the negative regulation pathways, and then the transcriptomic data are analyzed to determine whether this hypothesis is workable or not. Unexpectedly, the transcriptomic data reveal a negative regulation between <i>lasI</i> and <i>psqR</i>. Also, the individual cases from transcriptomic data demonstrate the negative regulations of PQS with <i>laslI, laslR</i>, <i>rhlI</i>, and <i>rhlR</i> under different experiments. Based on our analyses, possible strategies to reverse biofilm formation are proposed and their clinic implications are addressed.