Delving into the Latest Updates on Bactobolin with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms-

Target

Folate x thymidine kinase

Mechanism

Folate inhibitors, thymidine kinase inhibitors(Thymidine kinase inhibitors)

Therapeutic Areas

Infectious Diseases

Active Indication

MRSA - Methicillin resistant Staphylococcus aureus infection

Inactive Indication-

Originator Organization

University of Missouri-Kansas City

Active Organization

University of Missouri-Kansas City

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

AbstractToxins are believed to play a crucial role inBurkholderia pseudomalleipathogenicity, however to date, only a few have been identified. The discovery of additional toxic molecules is limited by the lack of a sensitive indicator ofB. pseudomalleitoxicity. Previously, from a whole genome transcriptome analysis ofB. pseudomallei-infectedCaenorhabditis elegans, we noted significant overexpression of a number of worm genes encoding detoxification enzymes, indicating the host’s attempt to clear bacterial toxic molecules. One of these genes,ugt–29, a family member of UDP-glucuronosyltransferases, was the most robustly induced phase II detoxification gene. In this study, we show that strong induction ofugt–29is restricted to infections by the most virulent species among the pathogens tested. We also noted thatugt–29is activated upon disruption of host protein synthesis. Hence, we propose that UGT–29 could be a promising biosensor to detectB. pseudomalleitoxins that compromise host protein synthesis. The identification of bactobolin, a polyketide-peptide hybrid molecule, as a toxic molecule ofB. pseudomalleifurther verifies the utilization of this surveillance system to search for bacterial toxins. Hence, augt–29based reporter should be useful in screening for other molecules that inhibit host protein synthesis.

100 Deals associated with Bactobolin

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