title: Pseudomonas quinolone signalling system: a component of quorum sensing cascade is a crucial player in the acute urinary tract infection caused by Pseudomonas aeruginosa.
abstract: Pseudomonas aeruginosa is an opportunistic pathogen which employs quorum sensing system to regulate several genes required for its survival and pathogenicity within the host. Besides acylhomoserine lactone (AHL) mediated las and rhl systems, this organism possesses Pseudomonas quinolone signalling (PQS) system based on alkyl quinolone signal molecules. The quinolone system represents another layer of sophistication in the complex quorum sensing cascade. Therefore, in the present study, we evaluated the contribution of the PQS system in the establishment of acute urinary tract infection (UTI) in the mouse model. For this, wild-type parent strain of P. aeruginosa MPAO1 and its isogenic single transposon mutant strains pqsH and pqsA were employed to induce UTI in mice. PQS molecules in the tissue homogenates of mice were detected by high performance thin layer chromatography (HP-TLC) method. Virulence of strains was assessed in terms of bacteriological count, histopathological lesions in the renal and bladder tissue and generation of pathological index markers like reactive nitrogen intermediates and malondialdehyde. HP-TLC analysis showed presence of PQS molecules in the renal and bladder tissue of mice infected with MPAO1 while no PQS was detected in case of pqsH and pqsA mutant strains. Results indicated that MPAO1 possessing fully functional PQS biosynthetic genes was highly virulent and caused acute pyelonephritis with severe inflammation and tissue destruction. On the contrary, significant reduction in the log count, mild tissue damage and declined levels of pathological markers were observed in mice infected with mutant strains as compared to MPAO1. Further among mutants, all these parameters were maximally impaired in the pqsA mutant in which synthesis of alkyl quinolones was completely abolished due to the transposon mutation in respective gene. Virulence of the pqsH mutant strain was lesser than that of the MPAO1 but higher than pqsA mutant. In addition, the levels of locally generated pro- and anti-inflammatory cytokines were also found to be low in the renal homogenates of mice infected with the mutant strains. Further, supplementation of strains with PQS resulted in significant enhancement in the virulence as indicated by increased bacterial load, severe histopathological damage and enhanced levels of pro-inflammatory cytokines. These findings provide a new insight into the relevant importance of the Pseudomonas quinolone signalling system in the acute UTI caused by P. aeruginosa. This system can be a potential target for futuristic anti-infective approach against this organism.
authors.affiliation: Department of Microbiology, BMS Block, Panjab University, Sector 14, Chandigarh 160014, India.
authors.forename: Anju
authors.initials: A
authors.lastname: Bala
authors.affiliation: Department of Microbiology, BMS Block, Panjab University, Sector 14, Chandigarh 160014, India.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Chhibber
authors.affiliation: Department of Microbiology, BMS Block, Panjab University, Sector 14, Chandigarh 160014, India. Electronic address: kusum_harjai@hotmail.com.
authors.forename: Kusum
authors.initials: K
authors.lastname: Harjai
mesh_terms: D000818:Animals; D058491:Bacterial Load; D004251:DNA Transposable Elements; D004195:Disease Models, Animal; D005260:Female; D055786:Gene Knockout Techniques; D006651:Histocytochemistry; D007668:Kidney / Q000382:microbiology / Q000473:pathology; D051379:Mice; D016254:Mutagenesis, Insertional; D011552:Pseudomonas Infections / Q000382:microbiology* / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology*; D015363:Quinolones / Q000378:metabolism*; D053038:Quorum Sensing; D012720:Severity of Illness Index; D015398:Signal Transduction; D001743:Urinary Bladder / Q000382:microbiology / Q000473:pathology; D014552:Urinary Tract Infections / Q000382:microbiology* / Q000473:pathology; D014774:Virulence
chemical_list: D004251:DNA Transposable Elements; D015363:Quinolones
keywords: Acute urinary tract infection; Pathogenicity; Pseudomonas aeruginosa; Pseudomonas quinolone signal; Quorum sensing