Analysis of quorum sensing-dependent virulence factor production and its relationship with antimicrobial susceptibility in Pseudomonas aeruginosa respiratory isolates

Abstract

Pseudomonas aeruginosa is an opportunistic pathogen causing severe respiratory infections. The pathogenesis of these infections is multifactorial and the production of many virulence factors is regulated by quorum sensing (QS), a cell-to-cell communication mechanism. The two well defined QS systems in P. aeruginosa, the las and rhl systems, rely on N-acyl homoserine lactone signal molecules, also termed autoinducers. We assessed the activity of QS-dependent virulence factors (including elastase, alkaline protease, pyocyanin and biofilm production) in respiratory isolates of P. aeruginosa and their relationship with antimicrobial susceptibility. We identified sixteen isolates displaying impaired phenotypic activity; among them, eleven isolates were also defective in autoinducer production, and therefore considered QS-deficient. Six of the QS-deficient isolates failed to amplify one or more of the four QS regulatory genes (lasI, lasR, rhlI, rhlR) with PCR: one isolate was negative for rhlR, two isolates were negative for rhlI and rhlR and three isolates were negative for all four genes. The isolates that were negative for virulence factor production were generally less susceptible to the antimicrobials and statistically significant correlations were observed between the lack of elastase production and resistance to piperacillin and ceftazidime; between failure in alkaline protease production and resistance to tobramycin, piperacillin, piperacillin-tazobactam, cefepime, imipenem and ciprofloxacin; and between failure in pyocyanin production and resistance to amikacin, tobramycin, ceftazidime, ciprofloxacin and ofloxacin. The results obtained indicate that, despite the pivotal role of QS in the pathogenesis of P. aeruginosa respiratory infections, QS-deficient strains are still capable of causing infections and tend to be less susceptible to antimicrobials.

A complex hierarchical quorum-sensing circuitry modulates phenazine gene expression in Pseudomonas aeruginosa

“…In the light of the published genomic data, further support for the idea that the las system positively regulates the expression of both rhlR and rhlI have been defined [5]. Other studies reported the regulation of pyocyanin by QS previously [10,15,16]. It was also documented that pseudomonas strains can express increased pyocyanin levels despite decreased expressions in one or both QS systems.…”

Anti-pathogenic Potential of Coral Associated Bacteria Isolated from Gulf of Mannar Against Pseudomonas aeruginosa

“…It has been reported that QS controls the regulation of virulence and biofilm formation that are 1000-fold more resistant to antibiotics [1].…”

“…Pseudomonas aeruginosa, an opportunistic pathogen causes infections in cystic fibrosis (CF), burns, wounds and pneumonia patients [1]. QS plays a major role in controlling the virulence of P. aeruginosa by regulating various virulence traits viz.…”

“…QS plays a major role in controlling the virulence of P. aeruginosa by regulating various virulence traits viz. LasA protease, LasB elastase, superoxide dismutase, alkaline protease, hydrogen cyanide, pyocyanin, pyoverdin, rhamnolipid and biofilm formation [1].…”

P. aeruginosa Quorum Sensing System and the Experimental Model of Chronic Respiratory Infection: Scientific Letter

“…In the study car ri ed out with cli ni cal spe ci mens, Ka ra tu na and Yagci no ted that even tho ugh QS had a key ro le in the res pi ra tory tract in fec ti ons ca u sed by P. ae ru gi no sa, the QS mu tant stra ins ha ving low sen si ti vity to an ti mic ro bi al agents might al so le ad to in fec ti on. 25 Ka ra man et al de ve lo ped pul mo nary in fec ti on mo del in rats by using PA O1 ve PA O JP2 (∆la sI/∆rhlI) re fe ren ce la bo ra tory stra ins with agar be ads met hod. 26 As a re sult of the qu an ti ta ti ve culti va ti on of bronc ho al ve o lar la va ge (BAL) and lung tis su es on the 14th day of the in fec ti on, re se arc hers re por ted a sig ni fi cant in cre a se in the bac te ri al count of the gro up in fec ted with wild-type stra ins com pa red to the gro up in fec ted with mu tant strains.…”