Biofilm Formation and Antibiotic Resistance Are Regulated by Quorum Sensing in Bacterial Pathogenicity.

Abstract

Background:
Quorum sensing (QS) is a multifaceted and tightly orchestrated cell-to-cell communiqué network that lets  microorganisms to detect their cell mass and coordinate the appearance of a group of genes by secreting, releasing and detecting small molecules called autoinducers. This regulatory network enables bacterial populations to perform as a multi-cellular system by coordinating physiological activity only at a critical cell density. Gram-negative bacteria typically use N-acyl homoserine lactones (AHLs) as the mediators of QS, whereas Gram-positive bacteria mainly rely on processed oligopeptides. The complexity and adaptability of microbial social behavior is further highlighted by the fact that the same microbial signaling molecule, called autoinducer-2 (AI-2), is involved in interspecies communication. This matrix provides physical and chemical barrier to antibiotic penetration, poor immune system recognition and heterogeneous microenvironments, which allows for bacterial persistence. The metabolic state of the microbial cells changes in biofilms, such as sluggish increasing or inactive “persister” cells that stand very resilient to antimicrobials and promote chronic and recurrent infections. The development and growth of biofilms are strictly regulated by genes associated with adhesion factors, EPS production, motility and stress response by QS systems. Importantly, QS also regulates the expression of virulence factors (toxins, enzymes, secretion systems etc.) which increases pathogenicity during infection. QS networks have been found to be central to the establishment of persistent infections, especially in the hospital environment where device-associated infections (e.g., catheters, ventilators, implants) are prevalent. The dense cellular agglomeration and extracellular DNA in the EPS matrix can contribute to processes of horizontal gene transfer (HGT) by transformation, transduction, and conjugation. QS can also trigger efflux pump systems, alter membrane permeability and induce activation of stress response pathways, all of which contribute to increasing the broadmindedness and confrontation of bacteria to antimicrobial agents. These mechanisms are especially a problem in multidrug-resistant (MDR) infections, in which traditional antibiotics are unable to kill biofilm-associated bacteria.