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SUMMARY:Cholesterol catabolism: An exploitable weakness in mycobacterial i
 nfections?
DTSTART;VALUE=DATE-TIME:20211125T073600Z
DTEND;VALUE=DATE-TIME:20211125T073700Z
DTSTAMP;VALUE=DATE-TIME:20260306T091245Z
UID:indico-contribution-4212@events01.synchrotron.org.au
DESCRIPTION:Speakers: Daniel Doherty (The University of Adelaide)\nFollowi
 ng the development of modern antibiotics and the net improvement of health
  care systems globally\, tuberculosis (TB)\, a contagious and pathogenic b
 acterial infection caused by *Mycobacterium tuberculosis*\, has been large
 ly eliminated from developed countries. Despite this improvement TB remain
 ed a top 10 cause of death globally in 2020\, which\, when combined with t
 he rise in multi-drug resistant tuberculosis (MDR-TB)\, represents an urge
 nt global health concern. Other pathogenic mycobacteria including *Mycobac
 terium ulcerans*\, the causative agent of Buruli Ulcer and *Mycobacterium 
 abscessus*\, a bacterium that affects cystic fibrosis patients\, are also 
 emerging public health threats. Mycobacteria are unique in their ability t
 o metabolise host cell cholesterol\, and this pathway has become a target 
 for new antibiotic treatments to drug-resistant infections. The cytochrome
  P450 enzymes of the CYP125\, CYP142 and CYP124 families initiate choleste
 rol metabolism. There are different numbers of cholesterol metabolising P4
 50s in each Mycobacterium species. For example\, *Mycobacterium ulcerans* 
 and *Mycobacterium tuberculosis* have one of each CYP125\, CYP142 and CYP1
 24 enzymes\, while *Mycobacterium abscessus* has four different CYP125 enz
 ymes and no copies of CYP142 and CYP124. The reasons for different P450 pr
 ofiles between mycobacteria remain unknown\, as does a mechanistic underst
 anding of the P450-mediated cholesterol oxidation. This project aims to un
 derstand the structural\, evolutionary and mechanistic differences between
  enzymes of these three families. Also\, screening of these enzymes as tar
 gets for a new class of cholesterol-based\, anti-tubercular inhibitors wil
 l be undertaken.\n\nhttps://events01.synchrotron.org.au/event/146/contribu
 tions/4212/
LOCATION:Online
URL:https://events01.synchrotron.org.au/event/146/contributions/4212/
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