Role of quorum sensing in bacterial infections

Abstract

Quorum sensing (QS) is cell communication that is widely used by bacterial pathogens to coordinate the expression of several collective traits, including the production of multiple virulence factors, biofilm formation, and swarming motility once a population threshold is reached. Several lines of evidence indicate that QS enhances virulence of bacterial pathogens in animal models as well as in human infections; however, its relative importance for bacterial pathogenesis is still incomplete. In this review, we discuss the present evidence from in vitro and in vivo experiments in animal models, as well as from clinical studies, that link QS systems with human infections. We focus on two major QS bacterial models, the opportunistic Gram negative bacteria Pseudomonas aeruginosa and the Gram positive Staphylococcus aureus, which are also two of the main agents responsible of nosocomial and wound infections. In addition, QS communication systems in other bacterial, eukaryotic pathogens, and even immune and cancer cells are also reviewed, and finally, the new approaches proposed to combat bacterial infections by the attenuation of their QS communication systems and virulence are also discussed.

Keywords: Animal models; Infections; Pseudomonas aeruginosa; Quorum sensing; Staphylococcus aureus; Virulence.

Figure 1

Structures of representative quorum sensing signal molecules of Pseudomonas aeruginosa. A: 3-oxo-C12-homoserine lactone; B: N-butyryl-L-homoserine lactone; C: 2-heptyl-3-hydroxy-4-quinolone; D: DSF-like fatty acids, cis-2-decenoic acid) and S. aureus (E: AIP group I).

Figure 2

Structures of quorum sensing inhibitors evaluated in animal models. A: Meta-bromo-thiolactone; B: Phenylacetic acid; C: 2,5-piperazinedione; D: Cucurmin; E: Furanone C-30; F: Furanone C-56; G: Ajoene 4,5,9,-trithiadodeca-1,6,11-triene-9-oxide; H: 2-amino-6-chlorobenzoic acid; I: 2-amino-6-fluorobenzoic acid; J: 2-amino-4-chlorobenzoic acid; K: AIP-II; L: RIP (H-Tyr-Ser-Pro-Trp-Thr-Asn-Phe-NH₂); M: FS8 (H-Tyr-Ser-Pro-Trp-Thr-Asn-Ala-NH₂).

Figure 3

Structures of representative quorum quenching molecules of Pseudomonas aeruginosa. A: Indole; B: 7-hidroxy indole; C: 7-fluoroindole; D: 5-fluorouracil; E: 2-chloro-N-methyl-maleimide; F: 1,3-benzoxazol-2(3H)-one; G: 5-cloro-1,3-benzoxazol-2(3H)-one (clorzoxazone); H: 5-methyl-1,3-benzoxazol-2(3H)-one; I: 6-methyl-1,3-benzoxazol-2(3H)-one; J: PD12; K: V-06-018; L: Niclosamide; M: Thimerosal; N: Phenylmercuric nitrate; O: Baicalein; P: 5-imino-4,6-dihydro-3H-1,2,3-triazolo[5,4-d]pyrimidin-7-one; Q: Patulin; R: Salicylic acid; S: 3-oxo-C12-(2-aminophenol); T: Nifuroxazide; U: 4-nitropyridine-N-oxide; V: Pyrimidine; W: N-decanoyl-L-homoserine benzyl ester; X: V23; Y: V30; Z: P1; A1: NAP; B1: PJ97A; C1: 6-CN; D1: 6-CF3; E1: 6-NO2; F1: Lyngbyoic acid; G1: Andrographolide 14-(5-cyclopentylvaleryl); H1: Emodin; I1: Goyazensolide-type; J1: Isogoyazensolide-type; K1: Iberin; L1: Allicin; M1: [6]-gingerol; N1: [6]-shogaol; O1: Zingerone and S. aureus; P1: Diflunisal; Q1: Hamamelitannin; R1: Cis-nerolidol; S1: Trans-stilbene; T1: Resveratrol.