scholarly journals Mycobacterium tuberculosis Genes Induced during Infection of Human Macrophages

2002 ◽  
Vol 70 (6) ◽  
pp. 2787-2795 ◽  
Author(s):  
Eugenie Dubnau ◽  
Patricia Fontán ◽  
Riccardo Manganelli ◽  
Sonia Soares-Appel ◽  
Issar Smith
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Fatty Acid ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Acyl Carrier Protein ◽  
Plasmid Vector ◽  
Mycolic Acid ◽  
Human Macrophages ◽  
Reverse Transcription Pcr ◽  
Promoter Trap

ABSTRACT We identified Mycobacterium tuberculosis genes preferentially expressed during infection of human macrophages using a promoter trap adapted for this pathogen. inhA encodes an enoyl-acyl carrier protein reductase that is required for mycolic acid biosynthesis (A. Quemard et al., Biochemistry 34:8235-8241, 1995) and is a major target for isoniazid (INH) in mycobacterial species (A. Banerjee et al., Science 263:227-230, 1994). Since overexpression of inhA confers INH resistance in Mycobacterium smegmatis (Banerjee et al., Science 263:227-230, 1994), we designed a promoter trap based on this gene. A library of clones, containing small fragments of M. tuberculosis DNA cloned upstream of inhA in a plasmid vector, was electroporated into M. tuberculosis, and the resulting culture was used to infect the human monocytic THP-1 cell line. Selection was made for clones surviving INH treatment during infection but retaining INH sensitivity on plates. The DNA upstream of inhA was sequenced in each clone to identify the promoter driving inhA expression. Thirteen genes identified by this method were analyzed by quantitative reverse transcription-PCR (R. Manganelli et al., Mol. Microbiol. 31:715-724, 1999), and eight of them were found to be differentially expressed from cultures grown in macrophages compared with broth-grown cultures. Several of these genes are presumed to be involved in fatty acid metabolism; one potentially codes for a unique DNA binding protein, one codes for a possible potassium channel protein, and the others code for proteins of unknown function. Genes which are induced during infection are likely to be significant for survival and growth of the pathogen; our results lend support to the view that fatty acid metabolism is essential for the virulence of M. tuberculosis.

scholarly journals Structure of a SLC26 Anion Transporter STAS Domain in Complex with Acyl Carrier Protein: Implications for E. coli YchM in Fatty Acid Metabolism

Structure ◽  
2010 ◽  
Vol 18 (11) ◽  
pp. 1450-1462 ◽  
Author(s):  
Mohan Babu ◽  
Jack F. Greenblatt ◽  
Andrew Emili ◽  
Natalie C.J. Strynadka ◽  
Reinhart A.F. Reithmeier ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Acyl Carrier Protein ◽  
Carrier Protein ◽  
E Coli ◽  
Anion Transporter ◽  
Stas Domain

scholarly journals Activity of Acyl Carrier Protein Isoforms in Reactions of Plant Fatty Acid Metabolism

1986 ◽  
Vol 82 (2) ◽  
pp. 448-453 ◽  
Author(s):  
Daniel J. Guerra ◽  
John B. Ohlrogge ◽  
Margrit Frentzen
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Acyl Carrier Protein ◽  
Protein Isoforms ◽  
Carrier Protein

scholarly journals The Role of Fatty Acid Metabolism in Drug Tolerance of Mycobacterium tuberculosis

mBio ◽  
2022 ◽  
Author(s):  
Camila G. Quinonez ◽  
Jae Jin Lee ◽  
Juhyeon Lim ◽  
Mark Odell ◽  
Christopher P. Lawson ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Fatty Acid ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Adaptive Strategies ◽  
Drug Tolerance ◽  
New Drugs ◽  
Acetate Medium ◽  
Tolerant State

Understanding the mechanisms underlying M. tuberculosis adaptive strategies to achieve drug tolerance is crucial for the identification of new targets and the development of new drugs. Here, we show that acetate medium triggers a drug-tolerant state in M. tuberculosis when challenged with antituberculosis (anti-TB) drugs.

scholarly journals Revisiting the Assignment of Rv0241c to Fatty Acid Synthase Type II of Mycobacterium tuberculosis

2010 ◽  
Vol 192 (15) ◽  
pp. 4037-4044 ◽  
Author(s):  
Emmanuelle Sacco ◽  
Nawel Slama ◽  
Kristina Bäckbro ◽  
Tanya Parish ◽  
Françoise Laval ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Acyl Carrier Protein ◽  
Mycolic Acid ◽  
Type Ii ◽  
Heterologous Complementation ◽  
Mycolic Acids ◽  
Fas Ii

ABSTRACT The fatty acid synthase type II enzymatic complex of Mycobacterium tuberculosis (FAS-II Mt ) catalyzes an essential metabolic pathway involved in the biosynthesis of major envelope lipids, mycolic acids. The partner proteins of this singular FAS-II system represent relevant targets for antituberculous drug design. Two heterodimers of the hydratase 2 protein family, HadAB and HadBC, were shown to be involved in the (3R)-hydroxyacyl-ACP dehydration (HAD) step of FAS-II Mt cycles. Recently, an additional member of this family, Rv0241c, was proposed to have the same function, based on the heterologous complementation of a HAD mutant of the yeast mitochondrial FAS-II system. In the present work, Rv0241c was able to complement a HAD mutant in the Escherichia coli model but not a dehydratase-isomerase deficient mutant. However, an enzymatic study of the purified protein demonstrated that Rv0241c possesses a broad chain length specificity for the substrate, unlike FAS-II Mt enzymes. Most importantly, Rv0241c exhibited a strict dependence on the coenzyme A (CoA) as opposed to AcpM, the natural acyl carrier protein bearing the chains elongated by FAS-II Mt . The deletion of Rv0241c showed that this gene is not essential to M. tuberculosis survival in vitro. The resulting mutant did not display any change in the mycolic acid profile. This demonstrates that Rv0241c is a trans-2-enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydratase that does not belong to FAS-II Mt . The relevance of a heterologous complementation strategy to identifying proteins of such a system is questioned.

Identification of small molecular ligands as potent inhibitors of fatty acid metabolism in Mycobacterium tuberculosis

2017 ◽  
Vol 1150 ◽  
pp. 227-241 ◽  
Author(s):  
Ramesh Malikanti ◽  
Rajender Vadija ◽  
Hymavathi Veeravarapu ◽  
Kiran Kumar Mustyala ◽  
Vasavi Malkhed ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Fatty Acid ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism

The Influence of Lactate and Dipyridamole on Myocardial Fatty Acid Metabolism in Man, Traced with 123l-17-lodo-heptadecanoic Acid

1990 ◽  
Vol 29 (01) ◽  
pp. 28-34 ◽  
Author(s):  
F. C. Visser ◽  
M. J. van Eenige ◽  
G. Westera ◽  
J. P. Roos ◽  
C. M. B. Duwel
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Time Activity ◽  
Time Value ◽  
Myocardial Fatty Acid Metabolism ◽  
Coronary Vasodilatation ◽  
Activity Curve ◽  
Normal Human ◽  
Plasma Lactate Level

Changes in myocardial metabolism can be detected externally by registration of time-activity curves after administration of radioiodinated fatty acids. In this scintigraphic study the influence of lactate on fatty acid metabolism was investigated in the normal human myocardium, traced with 123l-17-iodoheptadecanoic acid (123l-17-HDA). In patients (paired, n = 7) lactate loading decreased the uptake of 123l-17-HDA significantly from 27 (control: 22-36) to 20 counts/min/pixel (16-31; p <0.05 Wilcoxon). The half-time value increased to more than 60 rriin (n = 5), oxidation decreased from 61 to 42%. Coronary vasodilatation, a well-known side effect of lactate loading, was studied separately in a dipyridamole study (paired, n = 6). Coronary vasodilatation did not influence the parameters of the time-activity curve. These results suggest that changes in plasma lactate level as occurring, among other effects, during exercise will influence the parameters of dynamic 123l-17-HDA scintigraphy of the heart.

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