A structure activity-relationship study of the bacterial signal molecule HHQ reveals swarming motility inhibition in Bacillus atrophaeus

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Date
2015-04-16
Authors
Reen, F. Jerry
Shanahan, Rachel
Cano, Rafael
O'Gara, Fergal
McGlacken, Gerard P.
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The Royal Society of Chemistry
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Abstract
The sharp rise in antimicrobial resistance has been matched by a decline in the identification and clinical introduction of new classes of drugs to target microbial infections. Thus new approaches are being sought to counter the pending threat of a post-antibiotic era. In that context, the use of non-growth limiting small molecules, that target virulence behaviour in pathogens, has emerged as a solution with real clinical potential. We have previously shown that two signal molecules (HHQ and PQS) from the nosocomial pathogen Pseudomonas aeruginosa have modulatory activity towards other microorganisms. This current study involves the synthesis and evaluation of analogues of HHQ towards swarming and biofilm virulence behaviour in Bacillus atrophaeus, a soil bacterium and co-inhibitor with P. aeruginosa. Compounds with altered C6-C8 positions on the anthranilate-derived ring of HHQ, display a surprising degree of biological specificity, with certain candidates displaying complete motility inhibition. In contrast, anti-biofilm activity of the parent molecule was completely lost upon alteration at any position indicating a remarkable degree of specificity and delineation of phenotype.
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Keywords
Bacillus atrophaeus , Quinolones , Anti-microbial agent , Synthesis and evaluation of analogues of HHQ
Citation
REEN, F. J., SHANAHAN, R., CANO, R., O'GARA, F. & MCGLACKEN, G. P. 2015. A structure activity-relationship study of the bacterial signal molecule HHQ reveals swarming motility inhibition in Bacillus atrophaeus. Organic & Biomolecular Chemistry, 13, 5537-5541. http://dx.doi.org/10.1039/C5OB00315F