Colistin is an important cationic antimicrobial peptide (CAMP) in the fight against Pseudomonas aeruginosa infection in cystic fibrosis (CF) lungs. The effects of subinhibitory concentrations of colistin on gene expression in P. aeruginosa were investigated by transcriptome and functional genomic approaches. Analysis revealed altered expression of 30 genes representing a variety of pathways associated with virulence and bacterial colonization in chronic infection. These included response to osmotic stress, motility, and biofilm formation, as well as genes associated with LPS modification and quorum sensing (QS). Most striking was the upregulation of Pseudomonas quinolone signal (PQS) biosynthesis genes, including pqsH, pqsB and pqsE, and the phenazine biosynthesis operon. Induction of this central component of the QS network following exposure to subinhibitory concentrations of colistin may represent a switch to a more robust population, with increased fitness in the competitive environment of the CF lung.
BrazasM. D.,
HancockR. E.2005; Ciprofloxacin induction of a susceptibility determinant in Pseudomonas aeruginosa
. Antimicrob Agents Chemother 49:3222–3227
BredenbruchF.,
GeffersR.,
NimtzM.,
BuerJ.,
HäusslerS.2006; The Pseudomonas aeruginosa quinolone signal (PQS) has an iron-chelating activity. Environ Microbiol 8:1318–1329
CaoH.,
KrishnanG.,
GoumnerovB.,
TsongalisJ.,
TompkinsR.,
RahmeL. G.2001; A quorum sensing-associated virulence gene of Pseudomonas aeruginosa encodes a LysR-like transcription regulator with a unique self-regulatory mechanism. Proc Natl Acad Sci U S A 98:14613–14618
DézielE.,
LépineF.,
MilotS.,
HeJ.,
MindrinosM. N.,
TompkinsR. G.,
RahmeL. G.2004; Analysis of Pseudomonas aeruginosa 4-hydroxy-2-alkylquinolines (HAQs) reveals a role for 4-hydroxy-2-heptylquinoline in cell-to-cell communication. Proc Natl Acad Sci U S A 101:1339–1344
DiggleS. P.,
WinzerK.,
ChhabraS. R.,
WorrallK. E.,
CamaraM.,
WilliamsP.2003; The Pseudomonas aeruginosa quinolone signal molecule overcomes the cell density-dependency of the quorum sensing hierarchy, regulates rhl-dependent genes at the onset of stationary phase and can be produced in the absence of LasR. Mol Microbiol 50:29–43
DiggleS. P.,
MatthijsS.,
WrightV. J.,
FletcherM. P.,
ChhabraS. R.,
LamontI. L.,
KongX.,
HiderR. C.,
CornelisP.other authors2007; The Pseudomonas aeruginosa 4-quinolone signal molecules HHQ and PQS play multifunctional roles in quorum sensing and iron entrapment. Chem Biol 14:87–96
EvansM. E.,
FeolaD. J.,
RappR. P.1999; Polymyxin B sulfate and colistin: old antibiotics for emerging multiresistant Gram-negative bacteria. Ann Pharmacother 33:960–967
FletcherM. P.,
DiggleS. P.,
CamaraM.,
WilliamsP.2007; Biosensor-based assays for PQS, HHQ and related 2-alkyl-4-quinolone quorum sensing signal molecules. Nat Protoc 2:1254–1262
GerberM.,
WalchC.,
LöfflerB.,
TischendorfK.,
ReischlU.,
AckermannG.2008; Effect of sub-MIC concentrations of metronidazole, vancomycin, clindamycin and linezolid on toxin gene transcription and production in Clostridium difficile
. J Med Microbiol 57:776–783
GohE. B.,
YimG.,
TsuiW.,
McClureJ.,
SuretteM. G.,
DaviesJ.2002; Transcriptional modulation of bacterial gene expression by subinhibitory concentrations of antibiotics. Proc Natl Acad Sci U S A 99:17025–17030
GuinaT.,
PurvineS. O.,
YiE. C.,
EngJ.,
GoodlettD. R.,
AebersoldR.,
MillerS. I.2003; Quantitative proteomic analysis indicates increased synthesis of a quinolone by Pseudomonas aeruginosa isolates from cystic fibrosis airways. Proc Natl Acad Sci U S A 100:2771–2776
HäusslerS.,
BeckerT.2008; The pseudomonas quinolone signal (PQS) balances life and death in Pseudomonas aeruginosa populations. PLoS Pathog 4:e1000166
HawleyJ. S.,
MurrayC. K.,
JorgensenJ. H.2008; Colistin heteroresistance in Acinetobacter and its association with previous colistin therapy. Antimicrob Agents Chemother 52:351–352
HaysE. E.,
WellsI. C.,
KatzmanP. A.,
CainC. K.,
JacobsF. A.,
ThayerS. A.,
DoisyE. A.,
GabyW. L.,
RobertsE. C. & other authors; 1945; Antibiotic substances produced by Pseudomonas aeruginosa
. J Biol Chem 159:725–750
HermsenE. D.,
SullivanC. J.,
RotschaferJ. C.2003; Polymyxins: pharmacology, pharmacokinetics, pharmacodynamics, and clinical applications. Infect Dis Clin North Am 17:545–562
LabroM. T.,
el BennaJ.,
JemniA.1992; Alteration of bacteria induced by subinhibitory concentrations of cefixime: consequences on bactericidal activity of human polynuclear neutrophils. Pathol Biol(Paris )
40:427–432
LépineF.,
DézielE.,
MilotS.,
RahmeL. G.2003; A stable isotope dilution assay for the quantification of the Pseudomonas quinolone signal in Pseudomonas aeruginosa cultures. Biochim Biophys Acta 1622:36–41
LiangH.,
LiL.,
DongZ.,
SuretteM. G.,
DuanK.2008; The YebC family protein PA0964 negatively regulates the Pseudomonas aeruginosa quinolone signal system and pyocyanin production. J Bacteriol 190:6217–6227
LinaresJ. F.,
GustafssonI.,
BaqueroF.,
MartinezJ. L.2006; Antibiotics as intermicrobial signaling agents instead of weapons. Proc Natl Acad Sci U S A 103:19484–19489
MarkouN.,
ApostolakosH.,
KoumoudiouC.,
AthanasiouM.,
KoutsoukouA.,
AlamanosI.,
GregorakosL.2003; Intravenous colistin in the treatment of sepsis from multi-resistant Gram-negative bacilli in critically ill patients. Crit Care 7:R78–R83
MavrodiD. V.,
BonsallR. F.,
DelaneyS. M.,
SouleM. J.,
PhillipsG.,
ThomashowL. S.2001; Functional analysis of genes for biosynthesis of pyocyanin and phenazine-1-carboxamide from Pseudomonas aeruginosa PAO1. J Bacteriol 183:6454–6465
McGrathS.,
WadeD. S.,
PesciE. C.2004; Dueling quorum sensing systems in Pseudomonas aeruginosa control the production of the Pseudomonas quinolone signal (PQS. FEMS Microbiol Lett 230:27–34
MitovaM. I.,
LangG.,
WieseJ.,
ImhoffJ. F.2008; Subinhibitory concentrations of antibiotics induce phenazine production in a marine Streptomyces sp. J Nat Prod 71:824–827
OhJ. T.,
CajalY.,
SkowronskaE. M.,
BelkinS.,
ChenJ.,
Van DykT. K.,
SasserM.,
JainM. K.2000; Cationic peptide antimicrobials induce selective transcription of micF and osmY in Escherichia coli
. Biochim Biophys Acta146343–54
PesciE. C.,
MilbankJ. B.,
PearsonJ. P.,
McKnightS.,
KendeA. S.,
GreenbergE. P.,
IglewskiB. H.1999; Quinolone signaling in the cell-to-cell communication system of Pseudomonas aeruginosa
. Proc Natl Acad Sci U S A 96:11229–11234
RahmeL. G.,
AusubelF. M.,
CaoH.,
DrenkardE.,
GoumnerovB. C.,
LauG. W.,
Mahajan-MiklosS.,
PlotnikovaJ.,
TanM. W.other authors2000; Plants and animals share functionally common bacterial virulence factors. Proc Natl Acad Sci U S A 97:8815–8821
SavliH.,
KaradenizliA.,
KolayliF.,
GundesS.,
OzbekU.,
VahabogluH.2003; Expression stability of six housekeeping genes: a proposal for resistance gene quantification studies of Pseudomonas aeruginosa by real-time quantitative RT-PCR. J Med Microbiol 52:403–408
SpainkH. P.,
OkkerR. J. H.,
WijffelmanC. A.,
PeesE.,
LugtenbergB. J. J.1987; Promoters of nodulation region of the Rhizobium leguminosarum Sym plasmid pRL1J1. Plant Mol Biol 9:27–39
WadeD. S.,
CalfeeM. W.,
RochaE. R.,
LingE. A.,
EngstromE.,
ColemanJ. P.,
PesciE. C.2005; Regulation of Pseudomonas quinolone signal synthesis in Pseudomonas aeruginosa
. J Bacteriol 187:4372–4380
WaiteR. D.,
PapakonstantinopoulouA.,
LittlerE.,
CurtisM. A.2005; Transcriptome analysis of Pseudomonas aeruginosa growth: comparison of gene expression in planktonic cultures and developing and mature biofilms. J Bacteriol 187:6571–6576
WellsI. C.,
ElliottW. H.,
ThayerS. A.,
DoisyE. A.1952; Ozonization of some antibiotic substances produced by Pseudomonas aeruginosa
. J Biol Chem 196:321–330
WhiteleyM.,
BangeraM. G.,
BumgarnerR. E.,
ParsekM. R.,
TeitzelG. M.,
LoryS.,
GreenbergE. P.2001; Gene expression in Pseudomonas aeruginosa biofilms. Nature 413:860–864
YangL.,
BarkenK. B.,
SkindersoeM. E.,
ChristensenA. B.,
GivskovM.,
Tolker-NielsenT.2007; Effects of iron on DNA release and biofilm development by Pseudomonas aeruginosa
. Microbiology 153:1318–1328