Application of Chemical Genomics to Plant–Bacteria Communication: A High-Throughput System to Identify Novel Molecules Modulating the Induction of Bacterial Virulence Genes by Plant Signals

2017 ◽  
pp. 297-314 ◽  
Author(s):  
Elodie Vandelle ◽  
Maria Rita Puttilli ◽  
Andrea Chini ◽  
Giulia Devescovi ◽  
Vittorio Venturi ◽  
...  
Keyword(s):  
High Throughput ◽  
Virulence Genes ◽  
Bacterial Virulence ◽  
Chemical Genomics ◽  
Plant Signals

scholarly journals Redox, amino acid, and fatty acid metabolism intersect with bacterial virulence in the gut

2018 ◽  
Vol 115 (45) ◽  
pp. E10712-E10719 ◽  
Author(s):  
Reed Pifer ◽  
Regan M. Russell ◽  
Aman Kumar ◽  
Meredith M. Curtis ◽  
Vanessa Sperandio
Keyword(s):  
Fatty Acid ◽  
High Throughput ◽  
Fatty Acid Metabolism ◽  
Metabolic Pathways ◽  
Virulence Genes ◽  
Acid Metabolism ◽  
Feedback Mechanism ◽  
Regulatory Pathways ◽  
Successful Infection ◽  
Cellular Circuits

The gut metabolic landscape is complex and is influenced by the microbiota, host physiology, and enteric pathogens. Pathogens have to exquisitely monitor the biogeography of the gastrointestinal tract to find a suitable niche for colonization. To dissect the important metabolic pathways that influence virulence of enterohemorrhagicEscherichia coli(EHEC), we conducted a high-throughput screen. We generated a dataset of regulatory pathways that control EHEC virulence expression under anaerobic conditions. This unraveled that the cysteine-responsive regulator, CutR, converges with the YhaO serine import pump and the fatty acid metabolism regulator FadR to optimally control virulence expression in EHEC. CutR activates expression of YhaO to increase activity of the YhaJ transcription factor that has been previously shown to directly activate the EHEC virulence genes. CutR enhances FadL, which is a pump for fatty acids that represses inhibition of virulence expression by FadR, unmasking a feedback mechanism responsive to metabolite fluctuations. Moreover, CutR and FadR also augment murine infection byCitrobacter rodentium, which is a murine pathogen extensively employed as a surrogate animal model for EHEC. This high-throughput approach proved to be a powerful tool to map the web of cellular circuits that allows an enteric pathogen to monitor the gut environment and adjust the levels of expression of its virulence repertoire toward successful infection of the host.

scholarly journals An AlphaScreenTM-Based High-Throughput Screen to Identify Inhibitors of Hsp90-Cochaperone Interaction

2009 ◽  
Vol 14 (3) ◽  
pp. 273-281 ◽  
Author(s):  
Fang Yi ◽  
Pingjun Zhu ◽  
Noel Southall ◽  
James Inglese ◽  
Christopher P. Austin ◽  
...  
Keyword(s):  
High Throughput ◽  
Drug Target ◽  
Essential Role ◽  
High Throughput Screen ◽  
Chemical Probes ◽  
Chemical Genomics ◽  
Hsp90 Inhibitors ◽  
Hsp90 Function ◽  
Good Agreement

Hsp90 has emerged as an important anticancer drug target because of its essential role in promoting the folding and maturation of many oncogenic proteins. The authors describe the development of the first high-throughput screen, based on AlphaScreen™ technology, to identify a novel type of Hsp90 inhibitors that interrupt its interaction with the cochaperone HOP. The assay used the 20-mer C-terminal peptide of Hsp90 and the TPR2A domain of HOP. Assay specificity was demonstrated by measuring different interactions using synthetic peptides, with measured IC50s in good agreement with reported values. The assay was stable over 12 h and tolerated DMSO up to 5%. The authors first validated the assay by screening against 20,000 compounds in a 384-well format. After further optimization into a 1536-well format, it was screened against an NIH Chemical Genomics Center library of 76,134 compounds, with a signal-to-background ratio of 78 and Z′ factor of 0.77. The present assay can be used for discovery of novel small-molecule Hsp90 inhibitors that can be used as chemical probes to investigate the role of cochaperones in Hsp90 function. Such molecules have the potential to be developed into novel anticancer drugs, for use alone or in combination with other Hsp90 inhibitors. ( Journal of Biomolecular Screening 2009:273-281)

scholarly journals Phage-mediated Dispersal of Biofilm and Distribution of Bacterial Virulence Genes Is Induced by Quorum Sensing

2015 ◽  
Vol 11 (2) ◽  
pp. e1004653 ◽  
Author(s):  
Friederike S. Rossmann ◽  
Tomas Racek ◽  
Dominique Wobser ◽  
Jacek Puchalka ◽  
Elaine M. Rabener ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Virulence Genes ◽  
Bacterial Virulence

Bacteriophage-mediated spread of bacterial virulence genes

2015 ◽  
Vol 23 ◽  
pp. 171-178 ◽  
Author(s):  
José R Penadés ◽  
John Chen ◽  
Nuria Quiles-Puchalt ◽  
Nuria Carpena ◽  
Richard P Novick
Keyword(s):  
Virulence Genes ◽  
Bacterial Virulence

scholarly journals ASSAYS TO DETERMINE CHERRY ROOTSTOCK TOLERANCE TO “BACTERIAL CANKER” (PSEUDOMONAS SYRINGAE PV. SYRINGAE)

HortScience ◽  
1990 ◽  
Vol 25 (9) ◽  
pp. 1123f-1123
Author(s):  
Elzbieta Krzesinska ◽  
Anita Nina Miller
Keyword(s):  
Pseudomonas Syringae ◽  
Virulence Genes ◽  
Avirulent Strain ◽  
Bacterial Canker ◽  
Aqueous Extracts ◽  
Virulent Strains ◽  
Plant Signals ◽  
One Year

An excised twig assay was developed to evaluate cherry genotypes for their tolerance to Pseudomonas syringae pv. syringae. One-year-old wood was collected at monthly intervals from Oct. until Jan. of `Napoleon', `Corum', and a number of cherry rootstock. The rootstock included F/12-1, Giessen (GI), and M×M selections. Twigs were inoculated with one avirulent and three virulent strains. Evaluation of incision browning, callus, and gummosis production were made after incubation for 3 weeks. Based on gummosis is and browning ratings, all the rootstocks tested were found to be more tolerant than `Napoleon' and `Corum' to the 3 strains of Pseudomonas syringae used. No gummosis or browning was observed on twigs inoculated with water or the avirulent strain.Plant signals extracted from cherry leaves have been shown to control expression of virulence genes in P. syringae. Crude aqueous extracts from `Napoleon' twigs induced the syrB::1acZ fusion in P. syringae strain B3AR132 Other rootstocks are currently being evaluated for their ability to induce virulence in P. syringae pv. syringae,

scholarly journals High-Throughput Approaches for the Identification of Pseudomonas aeruginosa Antivirulents

mBio ◽  
2021 ◽  
Vol 12 (3) ◽  
Author(s):  
Donghoon Kang ◽  
Liyang Zhang ◽  
Natalia V. Kirienko
Keyword(s):  
Pseudomonas Aeruginosa ◽  
High Throughput ◽  
Bacterial Virulence ◽  
Special Focus ◽  
Content Type ◽  
Opportunistic Human Pathogen ◽  
New Treatments ◽  
High Throughput Screens ◽  
Synthetic Small Molecule ◽  
New Strategies

ABSTRACT Antimicrobial resistance is a serious medical threat, particularly given the decreasing rate of discovery of new treatments. Although attempts to find new treatments continue, it has become clear that merely discovering new antimicrobials, even if they are new classes, will be insufficient. It is essential that new strategies be aggressively pursued. Toward that end, the search for treatments that can mitigate bacterial virulence and tilt the balance of host-pathogen interactions in favor of the host has become increasingly popular. In this review, we will discuss recent progress in this field, with a special focus on synthetic small molecule antivirulents that have been identified from high-throughput screens and on treatments that are effective against the opportunistic human pathogen Pseudomonas aeruginosa.

scholarly journals Identification and analysis of bacterial virulence genes in vivo

2000 ◽  
Vol 355 (1397) ◽  
pp. 613-622 ◽  
Author(s):  
Kate E. Unsworth ◽  
David W. Holden
Keyword(s):  
Type Iii Secretion ◽  
Virulence Genes ◽  
Screening Method ◽  
Secretion System ◽  
Bacterial Virulence ◽  
Microbial Pathogens ◽  
Temperature Sensitive ◽  
Approaches To Study

Signature–tagged mutagenesis is a mutation–based screening method for the identification of virulence genes of microbial pathogens. Genes isolated by this approach fall into three classes: those with known biochemical function, those of suspected function and some whose functions cannot be predicted from database searches. A variety of in vitro and in vivo methods are available to elucidate the function of genes of the second and third classes. We describe the use of some of these approaches to study the function of the Salmonella pathogenicity island 2 type III secretion system of Salmonella typhimurium . This virulence determinant is required for intracellular survival. Secretion by this system is induced by an acidic pH, and its function may be to alter trafficking of the Salmonella –containing vacuole. Use of a temperature–sensitive non–replicating plasmid and competitive index tests with other genes show that in vivo phenotypes do not always correspond to those predicted from in vitro studies.

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