Phosphorylation and Processing of the Quorum-Sensing Molecule Autoinducer-2 in Enteric Bacteria

2007 ◽  
Vol 2 (2) ◽  
pp. 128-136 ◽  
Author(s):  
Karina B. Xavier ◽  
Stephen T. Miller ◽  
Wenyun Lu ◽  
Jeong Hwan Kim ◽  
Joshua Rabinowitz ◽  
...  
2019 ◽  
Vol 20 (12) ◽  
pp. 3112 ◽  
Author(s):  
Viviana Gatta ◽  
Polina Ilina ◽  
Alison Porter ◽  
Stuart McElroy ◽  
Päivi Tammela

Since quorum sensing (QS) is linked to the establishment of bacterial infection, its inactivation represents one of the newest strategies to fight bacterial pathogens. LsrK is a kinase playing a key role in the processing of autoinducer-2 (AI-2), a quorum-sensing mediator in gut enteric bacteria. Inhibition of LsrK might thus impair the quorum-sensing cascade and consequently reduce bacterial pathogenicity. Aiming for the development of a target-based assay for the discovery of LsrK inhibitors, we evaluated different assay set-ups based on ATP detection and optimized an automation-compatible method for the high-throughput screening of chemical libraries. The assay was then used to perform the screening of a 2000-compound library, which provided 12 active compounds with an IC50 ≤ 10 µM confirming the effectiveness and sensitivity of our assay. Follow-up studies on the positive hits led to the identification of two compounds, harpagoside and rosolic acid, active in a cell-based AI-2 QS interference assay, which are at the moment the most promising candidates for the development of a new class of antivirulence agents based on LsrK inhibition.


Microbiology ◽  
2003 ◽  
Vol 149 (7) ◽  
pp. 1859-1869 ◽  
Author(s):  
Joanne E. Dove ◽  
Kazutoyo Yasukawa ◽  
Colin R. Tinsley ◽  
Xavier Nassif

Neisseria meningitidis is a Gram-negative bacterium which is an important causative agent of septicaemia and meningitis. LuxS has been shown to be involved in the biosynthesis of a quorum sensing molecule, autoinducer-2 (AI-2), known to play a role in virulence in Escherichia coli, as well as other bacteria. Evidence that serogroup B of N. meningitidis produces AI-2, along with the observation that a luxS mutant of this strain had attenuated virulence in an infant rat model of bacteraemia, led to further investigation of the role of this quorum sensing molecule in N. meningitidis. In this study, it is demonstrated that AI-2 is not involved in regulating growth of meningococci, either in culture or in contact with epithelial cells. Furthermore, transcriptional profiling using DNA microarrays shows an absence of the concerted regulation seen in other bacteria. Taken together, these data suggest that in N. meningitidis, AI-2 may be a metabolic by-product and not a cell-to-cell signalling molecule.


2021 ◽  
Vol 20 (5) ◽  
pp. 1285-1295
Author(s):  
Bolin Fan ◽  
Lixia Pan ◽  
Zhongliang Wang ◽  
Eakapol Wangkahart ◽  
Yuchong Huang ◽  
...  

2015 ◽  
Vol 11 (12) ◽  
pp. e1005307 ◽  
Author(s):  
Sylvia Simon ◽  
Ursula Schell ◽  
Natalie Heuer ◽  
Dominik Hager ◽  
Michael F. Albers ◽  
...  

2008 ◽  
Vol 74 (6) ◽  
pp. 1798-1804 ◽  
Author(s):  
Henriette Geier ◽  
Serge Mostowy ◽  
Gerard A. Cangelosi ◽  
Marcel A. Behr ◽  
Timothy E. Ford

ABSTRACT Mycobacterium avium is an environmental organism and opportunistic pathogen with inherent resistance to drugs, environmental stresses, and the host immune response. To adapt to these disparate conditions, M. avium must control its transcriptional response to environmental cues. M. avium forms biofilms in various environmental settings, including drinking water pipes and potable water reservoirs. In this study, we investigated the role of the universal signaling molecule autoinducer-2 (AI-2) in biofilm formation by M. avium. The addition of the compound to planktonic M. avium cultures resulted in increased biofilm formation. Microarray and reverse transcriptase PCR studies revealed an upregulation of the oxidative stress response upon addition of AI-2. This suggests that the response to AI-2 might be related to oxidative stress, rather than quorum sensing. Consistent with this model, addition of hydrogen peroxide, a known stimulus of the oxidative stress response, to M. avium cultures resulted in elevated biofilm formation. These results suggest that AI-2 does not act as a quorum-sensing signal in M. avium. Instead, biofilm formation is triggered by environmental stresses of biotic and abiotic origins and AI-2 may exert effects on that level.


2004 ◽  
Vol 43 (16) ◽  
pp. 2106-2108 ◽  
Author(s):  
Michael M. Meijler ◽  
Louis G. Hom ◽  
Gunnar F. Kaufmann ◽  
Kathleen M. McKenzie ◽  
Chengzao Sun ◽  
...  

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