Abstract
The emergence and the dissemination of multidrug-resistant bacteria constitute a major public health issue. Among incriminated Gram-negative bacteria, Pseudomonas aeruginosa has been designated by the WHO as a critical priority threat. During the infection process, this pathogen secretes various virulence factors in order to adhere and colonize host tissues. Furthermore, P. aeruginosa has the capacity to establish biofilms that reinforce its virulence and intrinsic drug resistance. The regulation of biofilm and virulence factor production of this micro-organism is controlled by a specific bacterial communication system named Quorum Sensing (QS). The development of anti-virulence agents targeting QS that could attenuate P. aeruginosa pathogenicity without affecting its growth seems to be a promising new therapeutic strategy. This could prevent the selective pressure put on bacteria by the conventional antibiotics that cause their death and promote resistant strain survival. This review describes the QS-controlled pathogenicity of P. aeruginosa and its different specific QS molecular pathways, as well as the recent advances in the development of innovative QS-quenching anti-virulence agents to fight anti-bioresistance.
Highlights
The emergence and the dissemination of multidrug-resistant (MDR) bacteria constitute a major public health issue
Biofilm development plays an important role in the transmission of exogenous and endogenous nosocomial infections, providing to pathogens the ability to persist on abiotic surfaces, such as in the adhesion to mucous membranes, proteolytic enzymes and siderophores favouring the colonization of tissues, exotoxins, different exoenzymes released by sophisticated secretion systems, rhamnolipids, and hydrogen cyanide, ensuring bacterial persistence by countering the immune system
The signal transmission by las and rhl circuits relies on the secretion of acyl-homoserine lactone (AHL)-type AIs: the N-(3-oxododecanoyl)-L-homoserine lactone for las system and the N-butanoyl-L-homoserine lactone (BHL) for the rhl one (Scheme 2)
Summary
The emergence and the dissemination of multidrug-resistant (MDR) bacteria constitute a major public health issue. In order to regulate biofilm development, this pathogen uses a specific bacterial communication system named Quorum Sensing (QS) This sophisticated network of intra- and inter-species interactions relies on the secretion and perception of small signalling molecules called autoinducers (AIs) [7]. Its cell wall is surrounded by a weakly permeable outer membrane which constitutes of lipopolysaccharide (LPS) endotoxins and selective porins This is associated with a flagella and pili, ensuring its adhesion to the substratum and its mobility; and, different sophisticated secretion systems are implicated in the production of virulence factors. Host tissue colonization is promoted by numerous QS-orchestrated microbial interactions These include collaborative or competitive relationships between P. aeruginosa and other species or strains of pathogens or with microbiota. These include collaborative or competitive relationships between P. aeruginosa and other species or strains of pathogens or with microbiota. (Figure 1)
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