Applications of small molecule activators and inhibitors of quorum sensing in Gram-negative bacteria

2012 ◽  
Vol 20 (9) ◽  
pp. 449-458 ◽  
Author(s):  
Warren R.J.D. Galloway ◽  
James T. Hodgkinson ◽  
Steven Bowden ◽  
Martin Welch ◽  
David R. Spring
Keyword(s):  
Quorum Sensing ◽  
Small Molecule ◽  
Gram Negative Bacteria ◽  
Gram Negative

Quorum Sensing in Gram-Negative Bacteria: Small-Molecule Modulation of AHL and AI-2 Quorum Sensing Pathways

2011 ◽  
Vol 111 (1) ◽  
pp. 28-67 ◽  
Author(s):  
Warren R. J. D. Galloway ◽  
James T. Hodgkinson ◽  
Steven D. Bowden ◽  
Martin Welch ◽  
David R. Spring
Keyword(s):  
Quorum Sensing ◽  
Small Molecule ◽  
Gram Negative Bacteria ◽  
Gram Negative

Chemical probe of AHL modulators on quorum sensing in Gram-Negative Bacteria and as antiproliferative agents: A review

2021 ◽  
Vol 226 ◽  
pp. 113864
Author(s):  
Maxwell Ampomah-Wireko ◽  
Chunying Luo ◽  
Yaquan Cao ◽  
Huanhuan Wang ◽  
Lauraine Nininahazwe ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Gram Negative Bacteria ◽  
Chemical Probe ◽  
Antiproliferative Agents ◽  
Gram Negative

scholarly journals β-Cyclodextrin Interaction with N-Hexanoyl Homoserine Lactone as Quorum Sensing Signal Produced in Gram-Negative Bacteria

2012 ◽  
Vol 37 (2) ◽  
pp. 315-318 ◽  
Author(s):  
Chigusa Okano ◽  
Marina Arai ◽  
Eri Nasuno ◽  
Ken-ichi Iimura ◽  
Tomohiro Morohoshi ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Homoserine Lactone ◽  
Gram Negative Bacteria ◽  
Gram Negative

scholarly journals Autoinducer 2 Signaling via the Phosphotransferase FruA Drives Galactose Utilization by Streptococcus pneumoniae , Resulting in Hypervirulence

mBio ◽  
2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Claudia Trappetti ◽  
Lauren J. McAllister ◽  
Austen Chen ◽  
Hui Wang ◽  
Adrienne W. Paton ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Quorum Sensing ◽  
Capsular Polysaccharide ◽  
The Body ◽  
Gram Negative Bacteria ◽  
Phosphotransferase System ◽  
Gram Positive ◽  
Gram Negative ◽  
Autoinducer 2 ◽  
Leloir Pathway

ABSTRACT Communication between bacterial cells is crucial for the coordination of diverse cellular processes that facilitate environmental adaptation and, in the case of pathogenic species, virulence. This is achieved by the secretion and detection of small signaling molecules called autoinducers, a process termed quorum sensing. To date, the only signaling molecule recognized by both Gram-positive and Gram-negative bacteria is autoinducer 2 (AI-2), synthesized by the metabolic enzyme LuxS ( S -ribosylhomocysteine lyase) as a by-product of the activated methyl cycle. Homologues of LuxS are ubiquitous in bacteria, suggesting a key role in interspecies, as well as intraspecies, communication. Gram-negative bacteria sense and respond to AI-2 via the Lsr ABC transporter system or by the LuxP/LuxQ phosphorelay system. However, homologues of these systems are absent from Gram-positive bacteria and the AI-2 receptor is unknown. Here we show that in the major human pathogen Streptococcus pneumoniae , sensing of exogenous AI-2 is dependent on FruA, a fructose-specific phosphoenolpyruvate-phosphotransferase system that is highly conserved in Gram-positive pathogens. Importantly, AI-2 signaling via FruA enables the bacterium to utilize galactose as a carbon source and upregulates the Leloir pathway, thereby leading to increased production of capsular polysaccharide and a hypervirulent phenotype. IMPORTANCE S. pneumoniae is a Gram-positive bacterium frequently carried asymptomatically in the human nasopharynx. However, in a proportion of cases, it can spread to other sites of the body, causing life-threatening diseases that translate into massive global morbidity and mortality. Our data show that AI-2 signaling via FruA promotes the transition of the pneumococcus from colonization to invasion by facilitating the utilization of galactose, the principal sugar available in the upper respiratory tract. AI-2-mediated upregulation of Leloir pathway enzymes results in increased production of capsular polysaccharide and hypervirulence in a murine intranasal challenge model. This identifies the highly conserved FruA phosphotransferase system as a target for new antimicrobials based on the disruption of this generic quorum-sensing system.

Quorum sensing between Gram-negative bacteria responsible for methane production in a complex waste sewage sludge consortium

2018 ◽  
Vol 103 (3) ◽  
pp. 1485-1495 ◽  
Author(s):  
Phuong Dong Thi Nguyen ◽  
Nurul Asyifah Mustapha ◽  
Kiwao Kadokami ◽  
Rodolfo Garcia-Contreras ◽  
Thomas K. Wood ◽  
...  
Keyword(s):  
Sewage Sludge ◽  
Quorum Sensing ◽  
Methane Production ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Waste Sewage Sludge

Variations on a Theme: Diverse N-Acyl Homoserine Lactone-Mediated Quorum Sensing Mechanisms in Gram-Negative Bacteria

2006 ◽  
Vol 89 (3-4) ◽  
pp. 167-211 ◽  
Author(s):  
Debra Smith ◽  
Jin-Hong Wang ◽  
Jane E. Swatton ◽  
Peter Davenport ◽  
Bianca Price ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Homoserine Lactone ◽  
Acyl Homoserine Lactone ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Variations On A Theme

scholarly journals A small-molecule inhibitor of BamA impervious to efflux and the outer membrane permeability barrier

2019 ◽  
Vol 116 (43) ◽  
pp. 21748-21757 ◽  
Author(s):  
Elizabeth M. Hart ◽  
Angela M. Mitchell ◽  
Anna Konovalova ◽  
Marcin Grabowicz ◽  
Jessica Sheng ◽  
...  
Keyword(s):  
Outer Membrane ◽  
Small Molecule ◽  
Cytoplasmic Membrane ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Permeability Barrier ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Bam Complex ◽  
Induced Aggregation

The development of new antimicrobial drugs is a priority to combat the increasing spread of multidrug-resistant bacteria. This development is especially problematic in gram-negative bacteria due to the outer membrane (OM) permeability barrier and multidrug efflux pumps. Therefore, we screened for compounds that target essential, nonredundant, surface-exposed processes in gram-negative bacteria. We identified a compound, MRL-494, that inhibits assembly of OM proteins (OMPs) by the β-barrel assembly machine (BAM complex). The BAM complex contains one essential surface-exposed protein, BamA. We constructed a bamA mutagenesis library, screened for resistance to MRL-494, and identified the mutation bamAE470K. BamAE470K restores OMP biogenesis in the presence of MRL-494. The mutant protein has both altered conformation and activity, suggesting it could either inhibit MRL-494 binding or allow BamA to function in the presence of MRL-494. By cellular thermal shift assay (CETSA), we determined that MRL-494 stabilizes BamA and BamAE470K from thermally induced aggregation, indicating direct or proximal binding to both BamA and BamAE470K. Thus, it is the altered activity of BamAE470K responsible for resistance to MRL-494. Strikingly, MRL-494 possesses a second mechanism of action that kills gram-positive organisms. In microbes lacking an OM, MRL-494 lethally disrupts the cytoplasmic membrane. We suggest that the compound cannot disrupt the cytoplasmic membrane of gram-negative bacteria because it cannot penetrate the OM. Instead, MRL-494 inhibits OMP biogenesis from outside the OM by targeting BamA. The identification of a small molecule that inhibits OMP biogenesis at the cell surface represents a distinct class of antibacterial agents.

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