Crucial components of mycobacterium type II fatty acid biosynthesis (Fas-II) and their inhibitors

Duan, Xiangke; Xiang, Xiaohong; Xie, Jianping

doi:10.1111/1574-6968.12597

Cited by 24 publications

(15 citation statements)

References 97 publications

(118 reference statements)

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“…FAS-I is accountable for de novo fatty acid (FA) synthesis to form FA chain elongation (16-24 carbons) and then lengthened by the FAS-II monofunctional enzymes to yield long-chain fatty acids (36-48 carbons) and mycolic acids. Mutation of monofunctional enzymes often provides drug resistance to the mycobacteria [165]. Flavonoids such as isoliquiritigenin, butein, fisetin and 2,2 ,4 -trihydroxychalcone prevent the growth of M. smegmatis by targeting the dehydratase enzyme of FAS-II [164].…”

Section: Inhibition Of Biofilm Formationmentioning

confidence: 99%

Efficacy and Mechanisms of Flavonoids against the Emerging Opportunistic Nontuberculous Mycobacteria

2020

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Nontuberculous mycobacteria (NTM) are the causative agent of severe chronic pulmonary diseases and is accountable for post-traumatic wound infections, lymphadenitis, endometritis, cutaneous, eye infections and disseminated diseases. These infections are extremely challenging to treat due to multidrug resistance, which encompasses the classical and existing antituberculosis agents. Hence, current studies are aimed to appraise the antimycobacterial activity of flavonoids against NTM, their capacity to synergize with pharmacological agents and their ability to block virulence. Flavonoids have potential antimycobacterial effects at minor quantities by themselves or in synergistic combinations. A cocktail of flavonoids used with existing antimycobacterial agents is a strategy to lessen side effects. The present review focuses on recent studies on naturally occurring flavonoids and their antimycobacterial effects, underlying mechanisms and synergistic effects in a cocktail with traditional agents.

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Section: Inhibition Of Biofilm Formationmentioning

confidence: 99%

Efficacy and Mechanisms of Flavonoids against the Emerging Opportunistic Nontuberculous Mycobacteria

2020

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“…Proteins involved in mycolic acid and phthiocerol dimycocerosate (PDIM) biosynthesis including FaS, FadD15, EchA11, HadB, MmaA3, and Pks13 were less abundant in lineage 7 ( Table 4 ). Fas-II component proteins (KasA, KasB, and HadB), carboxylases (AccA2, AccD2, and AccD6) ( Duan et al, 2014 ), and RV2006 involved in trehalose biosynthesis ( Kapopoulou et al, 2011 ) were less abundant in lineages 4 and 7. Fas forms an important interaction hub ( Figure 5A ).…”

Section: Resultsmentioning

confidence: 99%

“…Several proteins that have critical roles in lipid biosynthesis (mycolic acid and PDIM) were differentially expressed. Mycolic acids are vital components of the MTBC cell wall contributing to inherent drug resistance, growth and virulence ( Duan et al, 2014 ; Marrakchi et al, 2014 ). The synthesis of mycolic acids requires type I and type II fatty acid synthase (FAS).…”

Section: Discussionmentioning

confidence: 99%

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Lineage-Specific Proteomic Signatures in the Mycobacterium tuberculosis Complex Reveal Differential Abundance of Proteins Involved in Virulence, DNA Repair, CRISPR-Cas, Bioenergetics and Lipid Metabolism

et al. 2020

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Despite the discovery of the tubercle bacillus more than 130 years ago, its physiology and the mechanisms of virulence are still not fully understood. A comprehensive analysis of the proteomes of members of the human-adapted Mycobacterium tuberculosis complex (MTBC) lineages 3, 4, 5, and 7 was conducted to better understand the evolution of virulence and other physiological characteristics. Unique and shared proteomic signatures in these modern, pre-modern and ancient MTBC lineages, as deduced from quantitative bioinformatics analyses of high-resolution mass spectrometry data, were delineated. The main proteomic findings were verified by using immunoblotting. In addition, analysis of multiple genome alignment of members of the same lineages was performed. Label-free peptide quantification of whole cells from MTBC lineages 3, 4, 5, and 7 yielded a total of 38,346 unique peptides derived from 3092 proteins, representing 77% coverage of the predicted proteome. MTBC lineage-specific differential expression was observed for 539 proteins. Lineage 7 exhibited a markedly reduced abundance of proteins involved in DNA repair, type VII ESX-3 and ESX-1 secretion systems, lipid metabolism and inorganic phosphate uptake, and an increased abundance of proteins involved in alternative pathways of the TCA cycle and the CRISPR-Cas system as compared to the other lineages. Lineages 3 and 4 exhibited a higher abundance of proteins involved in virulence, DNA repair, drug resistance and other metabolic pathways. The high throughput analysis of the MTBC proteome by super-resolution mass spectrometry provided an insight into the differential expression of proteins between MTBC lineages 3, 4, 5, and 7 that may explain the slow growth and reduced virulence, metabolic flexibility, and the ability to survive under adverse growth conditions of lineage 7.

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“…INH is a frontline anti-TB drug that inhibits the mycobacterial enoyl-reductase InhA and its activity is dependent on KatG activation, the catalase peroxidase involved in the activation of isoniazid. InhA is an essential enzyme for the biosynthesis of a major component of the mycobacterial cell wall, mycolic acid, through fatty acid synthesis (FAS-II) system ( Duan et al, 2014 ). InhA is also a target for second line drug ethionamide ( Banerjee et al, 1994 ).…”

Section: Introductionmentioning

confidence: 99%

Identification and validation of the mode of action of the chalcone anti-mycobacterial compounds

et al. 2020

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Crucial components of mycobacterium type II fatty acid biosynthesis (Fas-II) and their inhibitors

Cited by 24 publications

References 97 publications

Efficacy and Mechanisms of Flavonoids against the Emerging Opportunistic Nontuberculous Mycobacteria

Efficacy and Mechanisms of Flavonoids against the Emerging Opportunistic Nontuberculous Mycobacteria

Lineage-Specific Proteomic Signatures in the Mycobacterium tuberculosis Complex Reveal Differential Abundance of Proteins Involved in Virulence, DNA Repair, CRISPR-Cas, Bioenergetics and Lipid Metabolism

Identification and validation of the mode of action of the chalcone anti-mycobacterial compounds

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