Competition Studies Confirm Two Major Barriers That Can Preclude the Spread of Resistance to Quorum-Sensing Inhibitors in Bacteria

被引:92
作者
Gerdt, Joseph P. [1 ]
Blackwell, Helen E. [1 ]
机构
[1] Univ Wisconsin, Dept Chem, Madison, WI 53706 USA
关键词
PSEUDOMONAS-AERUGINOSA VIRULENCE; GRAM-NEGATIVE BACTERIA; TARGETING VIRULENCE; SOCIAL EVOLUTION; COOPERATION; GENE; BIOFILM; PROMOTES; DNA;
D O I
10.1021/cb5004288
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The growing threat of antibiotic resistance necessitates the development of novel antimicrobial therapies. Antivirulence agents that target group-beneficial traits in microorganisms (i.e., phenotypes that help the cells surrounding the producer cell instead of selfishly benefiting only the producer cell) represent a new antimicrobial approach that may be robust against the spread of resistant mutants. One prominent group-beneficial antivirulence target in bacteria is quorum sensing (QS). While scientists are producing new QS inhibitors (QSIs) at an increasing pace for use as research tools and potential therapeutic leads, substantial work remains in empirically demonstrating a robustness against resistance. Herein we report the results of in vitro competition studies in Pseudomonas aeruginosa that explicitly confirm that two separate barriers can impede the spread of resistance to QSIs: (1) insufficient native QS signal levels prevent rare QSI-resistant bacteria from expressing their QS regulon, and (2) group-beneficial QS-regulated phenotypes produced by resistant bacteria are susceptible to cheating by QSI-sensitive neighbors, even when grown on a solid substrate with limited mixing to mimic infected tissue. These results underscore the promise of QSIs and other antivirulence molecules that target group beneficial traits as resistance-robust antimicrobial treatments and provide support for their further development.
引用
收藏
页码:2291 / 2299
页数:9
相关论文
共 59 条
[51]   Social cheating in Pseudomonas aeruginosa quorum sensing [J].
Sandoz, Kelsi M. ;
Mitzimberg, Shelby M. ;
Schuster, Martin .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (40) :15876-15881
[52]   A network of networks:: Quorum-sensing gene regulation in Pseudomonas aeruginosa [J].
Schuster, M ;
Greenberg, EP .
INTERNATIONAL JOURNAL OF MEDICAL MICROBIOLOGY, 2006, 296 (2-3) :73-81
[53]   Antibiotics and the resistant microbiome [J].
Sommer, Morten O. A. ;
Dantas, Gautam .
CURRENT OPINION IN MICROBIOLOGY, 2011, 14 (05) :556-563
[54]   Selective Chemical Inhibition of agr Quorum Sensing in Staphylococcus aureus Promotes Host Defense with Minimal Impact on Resistance [J].
Sully, Erin K. ;
Malachowa, Natalia ;
Elmore, Bradley O. ;
Alexander, Susan M. ;
Femling, Jon K. ;
Gray, Brian M. ;
DeLeo, Frank R. ;
Otto, Michael ;
Cheung, Ambrose L. ;
Edwards, Bruce S. ;
Sklar, Larry A. ;
Horswill, Alexander R. ;
Hall, Pamela R. ;
Gresham, Hattie D. .
PLOS PATHOGENS, 2014, 10 (06)
[55]   A Quorum-Sensing Antagonist Targets Both Membrane-Bound and Cytoplasmic Receptors and Controls Bacterial Pathogenicity [J].
Swem, Lee R. ;
Swem, Danielle L. ;
O'Loughlin, Colleen T. ;
Gatmaitan, Raleene ;
Zhao, Bixiao ;
Ulrich, Scott M. ;
Bassler, Bonnie L. .
MOLECULAR CELL, 2009, 35 (02) :143-153
[56]   Highly Potent Inhibitors of Quorum Sensing in Staphylococcus aureus Revealed Through a Systematic Synthetic Study of the Group-III Autoinducing Peptide [J].
Tal-Gan, Yftah ;
Stacy, Danielle M. ;
Foegen, Mary K. ;
Koenig, David W. ;
Blackwell, Helen E. .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2013, 135 (21) :7869-7882
[57]   Spatial Population Expansion Promotes the Evolution of Cooperation in an Experimental Prisoner's Dilemma [J].
Van Dyken, J. David ;
Mueller, Melanie J. I. ;
Mack, Keenan M. L. ;
Desai, Michael M. .
CURRENT BIOLOGY, 2013, 23 (10) :919-923
[58]   Cooperation and cheating in Pseudomonas aeruginosa: the roles of the las, rhl and pqs quorum-sensing systems [J].
Wilder, Cara N. ;
Diggle, Stephen P. ;
Schuster, Martin .
ISME JOURNAL, 2011, 5 (08) :1332-1343
[59]   Synthetic furanones inhibit quorum-sensing and enhance bacterial clearance in Pseudomonas aeruginosa lung infection in mice [J].
Wu, H ;
Song, Z ;
Hentzer, M ;
Andersen, JB ;
Molin, S ;
Givskov, M ;
Hoiby, N .
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 2004, 53 (06) :1054-1061