Abstract
Pseudomonas aeruginosa employs 2-heptyl-3-hydroxy-4(1H)-quinolone (the Pseudomonas quinolone signal, PQS) and 2-heptyl-4(1H)-quinolone (HHQ) as quorum sensing signal molecules, which contribute to a sophisticated regulatory network controlling the production of virulence factors and antimicrobials. We demonstrate that Mycobacterium abscessusT and clinical M. abscessus isolates are capable of degrading these alkylquinolone signals. Genome sequences of 50 clinical M. abscessus isolates indicated the presence of aqdRABC genes, contributing to fast degradation of HHQ and PQS, in M. abscessus subsp. abscessus strains, but not in M. abscessus subsp. bolletii and M. abscessus subsp. massiliense isolates. A subset of 18 M. a. subsp. abscessus isolates contained the same five single nucleotide polymorphisms (SNPs) compared to the aqd region of the type strain. Interestingly, representatives of these isolates showed faster PQS degradation kinetics than the M. abscessus type strain. One of the SNPs is located in the predicted promoter region of the aqdR gene encoding a putative transcriptional regulator, and two others lead to a variant of the AqdC protein termed AqdCII, which differs in two amino acids from AqdCI of the type strain. AqdC, the key enzyme of the degradation pathway, is a PQS dioxygenase catalyzing quinolone ring cleavage. While transcription of aqdR and aqdC is induced by PQS, transcript levels in a representative of the subset of 18 isolates were not significantly altered despite the detected SNP in the promoter region. However, purified recombinant AqdCII and AqdCI exhibit different kinetic properties, with approximate apparent Km values for PQS of 14 μM and 37 μM, and kcat values of 61 s-1 and 98 s-1, respectively, which may (at least in part) account for the observed differences in PQS degradation rates of the strains. In co-culture experiments of P. aeruginosa PAO1 and M. abscessus, strains harboring the aqd genes reduced the PQS levels, whereas mycobacteria lacking the aqd gene cluster even boosted PQS production. The results suggest that the presence and expression of the aqd genes in M. abscessus lead to a competitive advantage against P. aeruginosa.
Highlights
Pseudomonas aeruginosa is an opportunistic pathogen regulating its virulence via a complex quorum sensing (QS) network
Pseudomonas aeruginosa often dominates the microbiome of the lungs of adult cystic fibrosis (CF) patients, the CF lung is usually colonized with multiple pathogens
Alkylquinolones produced by P. aeruginosa, acting as QS signals and antimicrobials, have been detected in the sputum of CF patients (Collier et al, 2002; Barr et al, 2015)
Summary
Pseudomonas aeruginosa is an opportunistic pathogen regulating its virulence via a complex quorum sensing (QS) network. Several QS-regulated exoproducts of P. aeruginosa do contribute to establishing infections of the host, and act as antimicrobials. These may affect other species coexisting with P. aeruginosa in mixed microbial communities such as those infecting the lung of cystic fibrosis (CF) patients. Studies using laboratory co-cultures of P. aeruginosa with other bacteria support the hypothesis that QS-controlled exoproducts are important for competition. Hydrogen cyanide, rhamnolipids, and phenazines together promoted P. aeruginosa competitiveness in co-culture with Burkholderia multivorans, with hydrogen cyanide contributing the greatest effect (Smalley et al, 2015). In polymicrobial communities, bacteria capable of quenching the production of P. aeruginosa antimicrobials by interference with its QS systems should have some advantage for survival and growth
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