Halogenated furanones from the red alga,Delisea pulchra, inhibit carbapenem antibiotic synthesis and exoenzyme virulence factor production in the phytopathogenErwinia carotovora

Vibrio cholerae has been shown to produce a cyclic dipeptide, cyclo(phenylalanine–proline) (cFP), that functions to repress virulence factor production. The objective of this study was to determine if heterologous cyclic dipeptides could repress V. cholerae virulence factor production. To that end, three synthetic cyclic dipeptides that differed in their side chains from cFP were assayed for virulence inhibitory activity in V. cholerae. The results revealed that cyclo(valine–valine) (cVV) inhibited virulence factor production by a ToxR-dependent process that resulted in the repression of the virulence regulator aphA. cVV-dependent repression of aphA was found to be independent of known aphA regulatory genes. The results demonstrated that V. cholerae was able to respond to exogenous cyclic dipeptides and implicated the hydrophobic amino acid side chains on both arms of the cyclo dipeptide scaffold as structural requirements for inhibitory activity. The results further suggest that cyclic dipeptides have potential as therapeutics for cholera treatment.

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Impact ofd-amino acid dehydrogenase on virulence factor production by aPseudomonas aeruginosa

Canadian Journal of Microbiology ◽

10.1139/cjm-2013-0289 ◽

2013 ◽

Vol 59 (9) ◽

pp. 598-603 ◽

Cited By ~ 1

Author(s):

Kathryn E. Oliver ◽

Laura Silo-Suh

Keyword(s):

Amino Acid ◽

Virulence Factor ◽

Bacterial Pathogen ◽

Optimal Production ◽

Acid Dehydrogenase ◽

Amino Acid Dehydrogenase ◽

Factor Production ◽

Lung Dysfunction ◽

Production Of Hydrogen ◽

Virulence Factor Production

Chronic Pseudomonas aeruginosa infections remain the leading cause of lung dysfunction and mortality for cystic fibrosis (CF) patients. Many other bacteria inhabit the CF lung, but P. aeruginosa utilizes novel strategies that allow it to colonize this environment as the predominant bacterial pathogen. d-Amino acid dehydrogenase encoded by dadA is highly expressed by P. aeruginosa within the CF lung, and it is required for optimal production of hydrogen cyanide by some CF-adapted isolates. To better understand the increased significance of d-amino acid dehydrogenase in P. aeruginosa physiology, we characterized the contribution of the dad operon to virulence factor production. In this study, we determined that DadA is required for optimal production of pyocyanin, pyoverdine, and rhamnolipid by CF-adapted and non-CF-adapted isolates of P. aeruginosa. In addition, DadA is required for optimal production of alginate, biofilm formation, and virulence of a CF-adapted isolated of P. aeruginosa in an alfalfa seedling model of infection. Taken together, the results indicate that DadA plays a pleiotropic role in the production of important virulence factors by P. aeruginosa.

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The Vibrio cholerae RND efflux systems impact virulence factor production and adaptive responses via periplasmic sensor proteins

PLoS Pathogens ◽

10.1371/journal.ppat.1006804 ◽

2018 ◽

Vol 14 (1) ◽

pp. e1006804 ◽

Cited By ~ 15

Author(s):

X. Renee Bina ◽

Mondraya F. Howard ◽

Dawn L. Taylor-Mulneix ◽

Vanessa M. Ante ◽

Dillon E. Kunkle ◽

...

Keyword(s):

Vibrio Cholerae ◽

Virulence Factor ◽

Adaptive Responses ◽

Factor Production ◽

Sensor Proteins ◽

Virulence Factor Production

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Total Synthesis of Xanthoangelol B and Its Various Fragments: Toward Inhibition of Virulence Factor Production of Staphylococcus aureus

Journal of Medicinal Chemistry ◽

10.1021/acs.jmedchem.8b01012 ◽

2018 ◽

Vol 61 (23) ◽

pp. 10473-10487 ◽

Cited By ~ 1

Author(s):

Pushpak Mizar ◽

Rekha Arya ◽

Truc Kim ◽

Soyoung Cha ◽

Kyoung-Seok Ryu ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Total Synthesis ◽

Virulence Factor ◽

Factor Production ◽

Virulence Factor Production

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Indole Inhibits ToxR Regulon Expression inVibrio cholerae

Infection and Immunity ◽

10.1128/iai.00776-18 ◽

2019 ◽

Vol 87 (3) ◽

Cited By ~ 7

Author(s):

Mondraya F. Howard ◽

X. Renee Bina ◽

James E. Bina

Keyword(s):

Virulence Factor ◽

Virulence Gene ◽

Dependent Manner ◽

Content Type ◽

Virulence Gene Expression ◽

Type Vi Secretion ◽

Biofilm Production ◽

Factor Production ◽

Periplasmic Domain ◽

Virulence Factor Production

ABSTRACTIndole is a degradation product of tryptophan that functions as a signaling molecule in many bacteria. This includesVibrio cholerae, where indole was shown to regulate biofilm and type VI secretion in nontoxigenic environmental isolates. Indole is also produced by toxigenicV. choleraestrains in the human intestine, but its significance in the host is unknown. We investigated the effects of indole on toxigenicV. choleraeO1 El Tor during growth under virulence inducing conditions. The indole transcriptome was defined by RNA sequencing and showed widespread changes in the expression of genes involved in metabolism, biofilm production, and virulence factor production. In contrast, genes involved in type VI secretion were not affected by indole. We subsequently found that indole repressed genes involved inV. choleraepathogenesis, including the ToxR virulence regulon. Consistent with this, indole inhibited cholera toxin and toxin-coregulated pilus production in a dose-dependent manner. The effects of indole on virulence factor production and biofilm were linked to ToxR and the ToxR-dependent regulator LeuO. The expression ofleuOwas increased by exogenous indole and linked to repression of the ToxR virulence regulon. This process was dependent on the ToxR periplasmic domain, suggesting that indole was a ToxR agonist. This conclusion was further supported by results showing that the ToxR periplasmic domain contributed to indole-mediated increased biofilm production. Collectively, our results suggest that indole may be a niche-specific cue that can function as a ToxR agonist to modulate virulence gene expression and biofilm production inV. cholerae.

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