Is Quorum Sensing Interference a Viable Alternative to Treat Pseudomonas aeruginosa Infections?
Quorum sensing (QS) coordinates the expression of multiple virulence factors in Pseudomonas aeruginosa; hence its inhibition has been postulated as a new alternative to treat its infections. In particular, QS interference approaches claim that they attenuate bacterial virulence without directly decreasing bacterial growth and suggest that in vivo the immune system would control the infections. Moreover, since in vitro experiments performed in rich medium demonstrate that interfering with QS decreases the production of virulence factors without affecting bacterial growth it was assumed than in vivo therapies will minimize the selection of resistant strains. Therefore, the underlying assumptions toward an effective implementation of a successful Quorum sensing interference (QSI) therapy for treating P. aeruginosa infections are that (i) QS only exerts important effects in the regulation of virulence genes but it does not affect metabolic processes linked to growth, (ii) the expression of virulence factors is only positively regulated by QS, (iii) inhibition of virulence factors in vivo do not affect bacterial growth, (iv) the immune system of the infected patients will be able to get rid of the infections, and (v) the therapy will be effective in the strains that are actively producing the infections. Nevertheless, for QSI in P. aeruginosa, substantial experimental evidence against the validity of most of these assumptions has accumulated during the past years, suggesting that a far better understanding of its virulence and its behavior during infections is needed in order to design truly solid QSI therapeutic alternatives to combat this remarkable pathogen.
Department of Microbiology and Parasitology, Faculty of Medicine, National Autonomous University of Mexico Mexico City, Mexico.
Rodolfo
R
García-Contreras
Pseudomonas infections; clinical isolates; quorum quenching; quorum sensing (QS); resistance
Am J Physiol Gastrointest Liver Physiol. 2007 Jan;292(1):G134-42
16901993
Infect Immun. 2005 Apr;73(4):2504-14
15784597
Antimicrob Agents Chemother. 2007 Oct;51(10):3677-87
17620382
Infect Immun. 2002 Jun;70(6):3085-93
12011002
J Bacteriol. 2005 Jul;187(14):4875-83
15995202
PLoS One. 2014 Feb 12;9(2):e88743
24533146
Front Microbiol. 2011 Apr 05;2:65
21747788
Pathog Dis. 2015 Aug;73(6):ftv040
26048733
J Bacteriol. 2005 Jul;187(13):4327-37
15968041
PLoS Pathog. 2010 Jul 08;6(7):e1000989
20628566
Indian J Microbiol. 2016 Mar;56(1):1-18
26843692
Microbiology. 2007 Jul;153(Pt 7):2312-20
17600075
J Immunol. 2012 Jan 1;188(1):386-93
22131330
Nature. 2000 Aug 31;406(6799):959-64
10984043
EMBO J. 2003 Aug 1;22(15):3803-15
12881415
Crit Care Med. 2006 Mar;34(3):823-8
16505663
Microbiol Mol Biol Rev. 2012 Mar;76(1):46-65
22390972
ISME J. 2015 Jan;9(1):115-25
24936763
Pathog Dis. 2015 Mar;73(2):1-4
25722489
Antimicrob Agents Chemother. 2012 May;56(5):2314-25
22314537
Wei Sheng Wu Xue Bao. 2009 Sep;49(9):1158-64
20030052
J Bacteriol. 2003 Apr;185(7):2080-95
12644477
PLoS Pathog. 2010 May 06;6(5):e1000883
20463812
Protein Cell. 2015 Jan;6(1):26-41
25249263
PLoS Pathog. 2007 Sep 14;3(9):1229-39
17941706
Genome Biol. 2006;7(10):R90
17038190
J Am Chem Soc. 2015 Feb 4;137(4):1510-9
25574853
J Burn Care Rehabil. 1999 Jan-Feb;20(1 Pt 1):42-9
9934636
Microbiology. 2009 Mar;155(Pt 3):712-23
19246742
Infect Immun. 1999 Nov;67(11):5854-62
10531240
Nat Rev Microbiol. 2009 Sep;7(9):654-65
19680249
Environ Microbiol. 2015 Apr;17(4):960-8
24528485
Rev Infect Dis. 1983 Nov-Dec;5 Suppl 5:S998-1004
6419322
Infect Immun. 2014 Aug;82(8):3417-25
24891106
Microb Ecol. 2014 Jul;68(1):13-23
24194099
Mol Microbiol. 1999 Dec;34(5):1082-93
10594832
Antimicrob Agents Chemother. 2010 May;54(5):2219-24
20194693
J Clin Invest. 2003 Nov;112(10):1460-5
14617745
Proc Natl Acad Sci U S A. 2007 Oct 2;104(40):15876-81
17898171
J Bacteriol. 2007 Nov;189(22):8079-87
17873029
Int J Med Microbiol. 2010 Dec;300(8):534-43
20947426
Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):3129-34
11854465
J Biol Chem. 2012 Aug 3;287(32):27095-105
22665491
Crit Rev Microbiol. 2010 Nov;36(4):349-60
20846031
World J Clin Cases. 2015 Jul 16;3(7):575-98
26244150
Microbiology. 2005 Feb;151(Pt 2):373-83
15699188
Infect Immun. 2007 Oct;75(10):4885-90
17620352
Microbiology. 2010 Aug;156(Pt 8):2271-82
20488878
Microb Biotechnol. 2012 Jul;5(4):560-72
22414222
ISME J. 2016 Jan;10 (1):4-10
26023871
J Biomed Sci. 2008 Nov;15(6):731-41
18688758
ISME J. 2012 Mar;6(3):493-501
21918575
J Bacteriol. 2003 Apr;185(7):2066-79
12644476
BMC Genomics. 2014 Apr 28;15:318
24773920
PLoS Pathog. 2010 Mar 12;6(3):e1000810
20300606
J Bacteriol. 2005 Jun;187(11):3898-902
15901720
Proc Natl Acad Sci U S A. 2009 Apr 14;106(15):6327-32
19369215
J Med Microbiol. 1984 Aug;18(1):125-33
6431109
Proc Natl Acad Sci U S A. 2013 Oct 29;110(44):17981-6
24143808
Pathog Dis. 2013 Jun;68(1):8-11
23620228
JAMA. 2003 Oct 1;290(13):1749-56
14519709
BMC Microbiol. 2004 Jul 02;4:25
15233843
J Antimicrob Chemother. 2004 Jun;53(6):1054-61
15117922
Nature. 2007 Nov 15;450(7168):411-4
18004383
Appl Environ Microbiol. 2013 Nov;79(22):6840-6
24014536
Am J Respir Cell Mol Biol. 2007 Jan;36(1):1-7
16888286
J Bacteriol. 2015 Jun 15;197(12):2072-82
25868647