The quorum quenching antibody RS2-1G9 protects macrophages from the cytotoxic effects of the Pseudomonas aeruginosa quorum sensing signalling molecule N-3-oxo-dodecanoyl-homoserine lactone

Kaufmann, Gunnar F.; Park, Junguk; Mee, Jenny M.; Ulevitch, Richard J.; Janda, Kim D.

doi:10.1016/j.molimm.2008.01.010

Cited by 62 publications

(37 citation statements)

References 40 publications

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“…In order to overcome the small size of AHLs and to potentiate the maximal response for antibody generation, Janda and coworkers (104) pioneered a study where AHLs and AHL analogues were chemically conjugated to keyhole limpet hemocyanin (KLH) or bovine serum albumin (BSA), leading to efficient production of AHL-sequestering antibodies. These antibodies have shown very promising efficacy in protecting mice against P. aeruginosa infections (103,104,135).…”

Section: Targeting Bacterial Signalingmentioning

confidence: 99%

The Multiple Signaling Systems Regulating Virulence in Pseudomonas aeruginosa

Nadal‐Jimenez

Koch

Thompson

et al. 2012

Microbiol Mol Biol Rev

640

626

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SUMMARY Cell-to-cell communication is a major process that allows bacteria to sense and coordinately react to the fluctuating conditions of the surrounding environment. In several pathogens, this process triggers the production of virulence factors and/or a switch in bacterial lifestyle that is a major determining factor in the outcome and severity of the infection. Understanding how bacteria control these signaling systems is crucial to the development of novel antimicrobial agents capable of reducing virulence while allowing the immune system of the host to clear bacterial infection, an approach likely to reduce the selective pressures for development of resistance. We provide here an up-to-date overview of the molecular basis and physiological implications of cell-to-cell signaling systems in Gram-negative bacteria, focusing on the well-studied bacterium Pseudomonas aeruginosa . All of the known cell-to-cell signaling systems in this bacterium are described, from the most-studied systems, i.e., N -acyl homoserine lactones (AHLs), the 4-quinolones, the global activator of antibiotic and cyanide synthesis (GAC), the cyclic di-GMP (c-di-GMP) and cyclic AMP (cAMP) systems, and the alarmones guanosine tetraphosphate (ppGpp) and guanosine pentaphosphate (pppGpp), to less-well-studied signaling molecules, including diketopiperazines, fatty acids (diffusible signal factor [DSF]-like factors), pyoverdine, and pyocyanin. This overview clearly illustrates that bacterial communication is far more complex than initially thought and delivers a clear distinction between signals that are quorum sensing dependent and those relying on alternative factors for their production.

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Section: Targeting Bacterial Signalingmentioning

confidence: 99%

The Multiple Signaling Systems Regulating Virulence in Pseudomonas aeruginosa

Nadal‐Jimenez

Koch

Thompson

et al. 2012

Microbiol Mol Biol Rev

640

626

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“…Experiments confirmed that immunized mice had lower levels of free 3OC12HSL in both serum and lung homogenates than nonimmunized mice, and sera from immunized mice were able to protect macrophages from the cytotoxic effects of 3OC12HSL, suggesting that antibody targeting the AHL was responsible for protection following immunization (110). The MAb RS2-1G9 was also tested for its ability to protect murine macrophages from cytotoxicity effects of 3OC12HSL, and it was demonstrated that RS2-1G9 protected macrophages from 3OC12HSL-induced apoptosis in a concentration-dependent manner (111). As such, antibody sequestration of AHLs may be therapeutically beneficial by two routes, both by inhibiting activation of QS cascades and subsequent production of bacterial virulence factors and also by preventing host cell cytotoxicity induced by the AHL molecules themselves.…”

Section: Nonenzymatic Inactivation and Sequestration Of Qs Signals Usmentioning

confidence: 99%

Exploiting Quorum Sensing To Confuse Bacterial Pathogens

LaSarre

Federle

2013

Microbiol Mol Biol Rev

690

556

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SUMMARY Cell-cell communication, or quorum sensing, is a widespread phenomenon in bacteria that is used to coordinate gene expression among local populations. Its use by bacterial pathogens to regulate genes that promote invasion, defense, and spread has been particularly well documented. With the ongoing emergence of antibiotic-resistant pathogens, there is a current need for development of alternative therapeutic strategies. An antivirulence approach by which quorum sensing is impeded has caught on as a viable means to manipulate bacterial processes, especially pathogenic traits that are harmful to human and animal health and agricultural productivity. The identification and development of chemical compounds and enzymes that facilitate quorum-sensing inhibition (QSI) by targeting signaling molecules, signal biogenesis, or signal detection are reviewed here. Overall, the evidence suggests that QSI therapy may be efficacious against some, but not necessarily all, bacterial pathogens, and several failures and ongoing concerns that may steer future studies in productive directions are discussed. Nevertheless, various QSI successes have rightfully perpetuated excitement surrounding new potential therapies, and this review highlights promising QSI leads in disrupting pathogenesis in both plants and animals.

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“…Microbial processes like biofilm formation, virulence factor expression and bioluminescence are examples of QS-control. Recently, antivirulence therapies have drawn attention as a new strategy to combat microbial infections, and in that context bacterial QS represents a promising therapeutic target (Kaufmann et al, 2008). Even though toothbrushes and toothpastes have found wide usage, natural methods of teethcleaning using chewing sticks from a range of plants have been practiced for thousands of years in Asia, Africa, the Middle East and America.…”

Section: Introductionmentioning

confidence: 99%