Dataset Information

Raman2005 - Mycolic acid pathway of M. tuberculosis

ABSTRACT: The mycobacterial cell wall is a distinctive thick layer that protects the tubercle bacillus from general antibiotics and the host’s immune system. Mycolic acids, which are long-chain α-alkyl-β-hydroxy fatty acids, are the major constituents of this protective layer, and their synthesis has been shown to be critical for the survival of M. tuberculosis. This model captures the mycolic acid pathway in M. tuberculosis with 197 metabolites participating in 219 reactions catalysed by 28 proteins. The model helps in the rational identification of potential anti-tubercular drug targets.

SUBMITTER: Nicolas Le Novère

PROVIDER: BIOMD0000001046 | BioModels | 2024-09-02

REPOSITORIES: BioModels

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Dataset's files

Source:

			Action	DRS
	BIOMD0000001046?filename=MAP_FROG.zip	Other
	BIOMD0000001046?filename=MAP_MEMOTE.pdf	Pdf
	BIOMD0000001046?filename=MODEL8568434338-biopax2.owl	Owl
	BIOMD0000001046?filename=MODEL8568434338-biopax3.owl	Owl
	BIOMD0000001046?filename=MODEL8568434338.m	Other

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Publications

Flux balance analysis of mycolic acid pathway: targets for anti-tubercular drugs.

Raman Karthik K Rajagopalan Preethi P Chandra Nagasuma N

PLoS computational biology 20051014 5

Mycobacterium tuberculosis is the focus of several investigations for design of newer drugs, as tuberculosis remains a major epidemic despite the availability of several drugs and a vaccine. Mycobacteria owe many of their unique qualities to mycolic acids, which are known to be important for their growth, survival, and pathogenicity. Mycolic acid biosynthesis has therefore been the focus of a number of biochemical and genetic studies. It also turns out to be the pathway inhibited by front-line a ...[more]

PMID: 16261191

Similar Datasets

Project description:The capacity of Mycobacterium tuberculosis (Mtb) to sense, respond and adapt to variable and hostile environment within the host, has made it one of the most successful human pathogens. During different stages of infection, the bacillus is surrounding by a plethora of lipid rich molecules and current evidence points out the relevance of fatty acids during the Mtb infectious process. In this study, we have compared the transcriptional response of Mtb to hypoxia in cultures grown in both, a mix of even long-chain fatty acids and dextrose as carbon sources. Using RNA sequencing, we have identified the differential expressed genes in early and late hypoxia defined according to the in vitro Wayne model and compared the results with the exponential phase of growth in both carbon sources. Our results showed that, different to dextrose, the number of genes overexpressed in hypoxia in the lipid medium was quite low in both, early and late hypoxia in all functional categories describes for Mtb. The exception were the transcripts of stable and non-coding RNAs which were more expressed in the fatty acid medium. We found that SigB and SigE were overexpressed in the early phase of hypoxia, confirming their pivotal role in early adaptation to low oxygen concentration independently of the carbon source. A drastic contrast was found with the transcriptional regulatory factors at early hypoxia. Only 2 transcriptional factors were overexpressed in early hypoxia in the lipid medium compared to 37 that were overexpressed in the dextrose medium. Instead of Rv0081, known to be the central regulator of hypoxia in dextrose, Rv2745c, (ClgR), is playing a main role in hypoxia in the fatty acids medium. The low level of genes associated to stress-response, showed by Mtb during their adaptation to hypoxia in fatty acids, suggested that this lipid environment makes hypoxia a less stressful condition for the tubercle bacilli. Therefore, when the bacillus is surviving in that environment, its metabolism seemed to be already adapted to different stresses within the host, including hypoxia. This fact could explain the success of Mtb to establish long-term survival during latent infection.