AUTHOR=Chapalain Annelise , Groleau Marie-Christine , Le Guillouzer Servane , Miomandre Aurélie , Vial Ludovic , Milot Sylvain , Déziel Eric 

TITLE=Interplay between 4-Hydroxy-3-Methyl-2-Alkylquinoline and N-Acyl-Homoserine Lactone Signaling in a Burkholderia cepacia Complex Clinical Strain

JOURNAL=Frontiers in Microbiology

VOLUME=8

YEAR=2017

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2017.01021

DOI=10.3389/fmicb.2017.01021

ISSN=1664-302X

ABSTRACT=<p>Species from the <italic>Burkholderia cepacia</italic> complex (Bcc) share a canonical LuxI/LuxR quorum sensing (QS) regulation system named CepI/CepR, which mainly relies on the acyl-homoserine lactone (AHL), octanoyl-homoserine lactone (C<sub>8</sub>-HSL) as signaling molecule. <italic>Burkholderia ambifaria</italic> is one of the least virulent Bcc species, more often isolated from rhizospheres where it exerts a plant growth-promoting activity. However, clinical strains of <italic>B. ambifaria</italic> display distinct features, such as phase variation and higher virulence properties. Notably, we previously reported that under laboratory conditions, only clinical strains of the <italic>B. ambifaria</italic> species produced 4-hydroxy-3-methyl-2-alkylquinolines (HMAQs) <italic>via</italic> expression of the <italic>hmqABCDEFG</italic> operon. HMAQs are the methylated counterparts of the 4-hydroxy-2-alkylquinolines (HAQs) produced by the opportunistic human pathogen <italic>Pseudomonas aeruginosa</italic>, in which they globally contribute to the bacterial virulence and survival. We have found that unlike <italic>P. aeruginosa</italic>’s HAQs, HMAQs do not induce their own production. However, they indirectly regulate the expression of the <italic>hmqABCDEFG</italic> operon. In <italic>B. ambifaria</italic>, a strong link between CepI/CepR-based QS and HMAQs is proposed, as we have previously reported an increased production of C<sub>8</sub>-HSL in HMAQ-negative mutants. Here, we report the identification of all AHLs produced by the clinical <italic>B. ambifaria</italic> strain HSJ1, namely C<sub>6</sub>-HSL, C<sub>8</sub>-HSL, C<sub>10</sub>-HSL, 3OHC<sub>8</sub>-HSL, 3OHC<sub>10</sub>-HSL, and 3OHC<sub>12</sub>-HSL. Production of significant levels of hydroxylated AHLs prompted the identification of a second complete LuxI/LuxR-type QS system relying on 3OHC<sub>10</sub>-HSL and 3OHC<sub>12</sub>-HSL, that we have named CepI2/CepR2. The connection between these two QS systems and the <italic>hmqABCDEFG</italic> operon, responsible for HMAQs biosynthesis, was investigated. The CepI/CepR system strongly induced the operon, while the second system appears moderately involved. On the other hand, a HMAQ-negative mutant overproduces AHLs from both QS systems. Even if HMAQs are not classical QS signals, their effect on AHL-based QS system still gives them a part to play in the QS circuitry in <italic>B. ambifaria</italic> and thus, on regulation of various phenotypes.</p>