| Summary: | Pseudomonas aeruginosa is an opportunistic pathogen with a wide host range. It causes serious infection in cyctic fibrosis patients and patients with suppressed immunity. Most of the virulence and adaptational characters of this pathogen are controlled by quorum sensing. Quorum sensing in P. aeruginosa has two types of system, the first quorum sensing system is facilitated by N-acyl homoserine lactones which is further constituted by two system las and rhl system. The second type of quorum sensing system is facilitated by alkyl quinolones (AQ) and thus called the AQ signalling system. The AQ quorum sensing system plays a vital role in P. aeruginosa as it holds regulatory control over the rhl system and also is associated with the virulence factors such as pyocyanin, lectin and biofilm maturation. This system includes the phnA/B genes which produce the precursor molecule anthranilate and the pqsABCDE operon, which produces the first signal molecule 2-heptyl-4-quinolone (HHQ). HHQ gets converted to 2-heptyl-3hydroxy-4-quinolone also called Pseudomonas quinolone signal (PQS) which is the second signal molecule. The conversion of HHQ to PQS is facilitated by PqsH, an oxygen dependent monooxygenase which is not part of the pqsABCDE operon. PqsR, a transcriptional regulator of the LysR family of transcriptional regulator, holds transcriptional control over the phnA/B genes and pqsABCDDE operon. Avirulent phenotypes were observed with P. aeruginosa strains lacking PqsR, suggesting its important role in virulence. The cloning, expression, purification and crystal structure solution of PqsR coinducer binding domain has been described in this thesis. The structure of PqsR CBO shows a typical LTIR fold with 6 helices and 8 ~-strands. The structure also shows a unique dimer interface, unique hydrophobic pocket. In the apo-structure, two MPO molecules stabilised the hydrophobic pocket. The PqsR CBO - NHQ complex structure shows the ligand bound to the hydrophobic pocket with the quinolone head group buried deep within the protein and the alkyl chain bent and extending parallel to the dimer interface. PqsR is a potential anti-quorum sensing
|
|---|
