AUTHOR=Birmes Franziska S. , Wolf Timo , Kohl Thomas A. , Rüger Kai , Bange Franz , Kalinowski Jörn , Fetzner Susanne 

TITLE=Mycobacterium abscessus subsp. abscessus Is Capable of Degrading Pseudomonas aeruginosa Quinolone Signals

JOURNAL=Frontiers in Microbiology

VOLUME=8

YEAR=2017

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2017.00339

DOI=10.3389/fmicb.2017.00339

ISSN=1664-302X

ABSTRACT=<p><italic>Pseudomonas aeruginosa</italic> employs 2-heptyl-3-hydroxy-4(1<italic>H</italic>)-quinolone (the <italic>Pseudomonas</italic> quinolone signal, PQS) and 2-heptyl-4(1<italic>H</italic>)-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 <italic>Mycobacterium abscessus</italic><sup>T</sup> and clinical <italic>M. abscessus</italic> isolates are capable of degrading these alkylquinolone signals. Genome sequences of 50 clinical <italic>M. abscessus</italic> isolates indicated the presence of <italic>aqdRABC</italic> genes, contributing to fast degradation of HHQ and PQS, in <italic>M. abscessus</italic> subsp. <italic>abscessus</italic> strains, but not in <italic>M. abscessus</italic> subsp. <italic>bolletii</italic> and <italic>M. abscessus</italic> subsp. <italic>massiliense</italic> isolates. A subset of 18 <italic>M. a</italic>. subsp. <italic>abscessus</italic> isolates contained the same five single nucleotide polymorphisms (SNPs) compared to the <italic>aqd</italic> region of the type strain. Interestingly, representatives of these isolates showed faster PQS degradation kinetics than the <italic>M. abscessus</italic> type strain. One of the SNPs is located in the predicted promoter region of the <italic>aqdR</italic> gene encoding a putative transcriptional regulator, and two others lead to a variant of the AqdC protein termed AqdC<sup>II</sup>, which differs in two amino acids from AqdC<sup>I</sup> of the type strain. AqdC, the key enzyme of the degradation pathway, is a PQS dioxygenase catalyzing quinolone ring cleavage. While transcription of <italic>aqdR</italic> and <italic>aqdC</italic> 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 AqdC<sup>II</sup> and AqdC<sup>I</sup> exhibit different kinetic properties, with approximate apparent <italic>K</italic><sub>m</sub> values for PQS of 14 μM and 37 μM, and <italic>k</italic><sub>cat</sub> values of 61 s<sup>-1</sup> and 98 s<sup>-1</sup>, respectively, which may (at least in part) account for the observed differences in PQS degradation rates of the strains. In co-culture experiments of <italic>P. aeruginosa</italic> PAO1 and <italic>M. abscessus</italic>, strains harboring the <italic>aqd</italic> genes reduced the PQS levels, whereas mycobacteria lacking the <italic>aqd</italic> gene cluster even boosted PQS production. The results suggest that the presence and expression of the <italic>aqd</italic> genes in <italic>M. abscessus</italic> lead to a competitive advantage against <italic>P. aeruginosa</italic>.</p>