Cell Wall Biosynthesis and Latency During Tuberculosis Infections

Kurosu, Masaaki

doi:10.1007/978-3-030-25381-3_1

Cited by 4 publications

(5 citation statements)

References 58 publications

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“…Depending on the functional groups attached, the mycolic acids found in M. tb can be differentiated into α-, methoxy-, keto-, and/or hydroxy-mycolic acids. There are in total C66-C90 carbons in a mycolic acid chain length [27,30]. Even though mycolic acids are found in all mycobacterial pathogens and provide similar cellular protection, structural integrity, and virulence, The increasing incidence, limited efficacy of current treatment options, and significant risk of drug-resistance in NTM infections suggest an urgent need for new antimycobacterial agents.…”

Section: Mycolic Acid Biosynthesismentioning

confidence: 99%

“…Changing the 3-or 4-trifluoromethoxy to 2-trifluoromethoxy causes inactivity (MIC 50 > 100 µM). Cycloaliphatic rings such as cyclohexane or cycloheptane (27) showed highest potency against M. tb (MIC 50 = 3 µM), suggesting preference for bulkier cycloaliphatic groups. Replacement of 1-cyanocyclopentane with an aliphatic group such as 1-cyano-1-methyl-isopropyl causes only a slight decrease in activity (MIC 50 = 10 µM) and replacement with 1-cyano-1-methyl-cyclopropyl results in similar activity to that of the 26 (MIC 50 = 7 µM) [49].…”

Section: Quinoline and Quinolone Derivativesmentioning

confidence: 99%

“…The mycobacterial cell wall is different from the Gram-positive and -negative bacterial cell wall [ 27 ]. It is a complex structure, made up of covalently linked mycolic acids (MA)-peptidoglycan (PG)-arabinogalactan (AG) (also known as mAGP) [ 28 ].…”

Section: Mycolic Acid Biosynthesismentioning

confidence: 99%

“…The peptidoglycan is the innermost layer and mycolic acids are the outermost layer of the mycobacterial cell wall [ 28 ]. Mycolic acids are a major component and are considered a hallmark of the mycobacterial cell wall [ 27 , 29 , 30 ]. Mycolic acids comprise a highly impermeable lipid-rich layer that protects the mycobacterial cell against various threats including antibiotics and the host’s immune system and also contributes to virulence [ 30 , 31 ].…”

Section: Mycolic Acid Biosynthesismentioning

confidence: 99%

“…Marrakchi et al report InhA, MabA, HadB, and KasA as essential proteins [ 29 ]. In addition, KasB is essential for the full extension of the mycolic acids, the acid-fastness property of the mycobacteria, and production of ketomycolic acids [ 27 , 33 ]. The addition of cyclopropanes to the meromycolic acid is catalyzed by the S-adenosyl-methionine (SAM)-dependent methyltransferases.…”

Section: Mycolic Acid Biosynthesismentioning

confidence: 99%

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MmpL3 Inhibition: A New Approach to Treat Nontuberculous Mycobacterial Infections

Sethiya

Sowards

Jackson

et al. 2020

IJMS

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Outside of Mycobacterium tuberculosis and Mycobacterium leprae, nontuberculous mycobacteria (NTM) are environmental mycobacteria (>190 species) and are classified as slow- or rapid-growing mycobacteria. Infections caused by NTM show an increased incidence in immunocompromised patients and patients with underlying structural lung disease. The true global prevalence of NTM infections remains unknown because many countries do not require mandatory reporting of the infection. This is coupled with a challenging diagnosis and identification of the species. Current therapies for treatment of NTM infections require multidrug regimens for a minimum of 18 months and are associated with serious adverse reactions, infection relapse, and high reinfection rates, necessitating discovery of novel antimycobacterial agents. Robust drug discovery processes have discovered inhibitors targeting mycobacterial membrane protein large 3 (MmpL3), a protein responsible for translocating mycolic acids from the inner membrane to periplasm in the biosynthesis of the mycobacterial cell membrane. This review focuses on promising new chemical scaffolds that inhibit MmpL3 function and represent interesting and promising putative drug candidates for the treatment of NTM infections. Additionally, agents (FS-1, SMARt-420, C10) that promote reversion of drug resistance are also reviewed.

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Section: Mycolic Acid Biosynthesismentioning

confidence: 99%

Section: Quinoline and Quinolone Derivativesmentioning

confidence: 99%

Section: Mycolic Acid Biosynthesismentioning

confidence: 99%

Section: Mycolic Acid Biosynthesismentioning

confidence: 99%

Section: Mycolic Acid Biosynthesismentioning

confidence: 99%

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MmpL3 Inhibition: A New Approach to Treat Nontuberculous Mycobacterial Infections

Sethiya

Sowards

Jackson

et al. 2020

IJMS

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Nanotechnology‐Based Targeted Drug Delivery: An Emerging Tool to Overcome Tuberculosis

Baranyai

Soria‐Carrera

Alleva

et al. 2020

Advanced Therapeutics

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The appearance and rapid spread of drug resistant strains of tuberculosis (TB), one of the deadliest infectious diseases, pose a serious threat to public health and increase the need for shorter, less toxic, and more effective therapies. Developing new drugs is difficult and often associated with side effects, so nanotechnology has emerged as a tool to improve current treatments and to rescue drugs having elevated toxicity or poor solubility. Due to their size and surface chemistry, antimicrobial‐loaded nanocarriers are avidly taken up by macrophages, the main cells hosting Mycobacterium tuberculosis. Macrophages are continuously recruited to infected areas, they can transport drugs with them, making passive targeting a good strategy for TB treatment. Active targeting (decorating surface of nanocarriers with ligands specific to receptors displayed by macrophages) further increases local drug concentration, and thus treatment efficacy. Although in in vivo studies, nanocarriers are often administered intravenously in order to avoid inaccurate dosage in animals, translation to humans requires more convenient routes like pulmonary or oral administration. This report highlights the importance and progress of pulmonary administration, passive and active targeting strategies toward bacteria reservoirs to overcome the challenges in TB treatment.

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Pks 13 inhibitors—a promising target for future antitubercular agents

Deb

2023

Med Chem Res

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Cell Wall Biosynthesis and Latency During Tuberculosis Infections

Cited by 4 publications

References 58 publications

MmpL3 Inhibition: A New Approach to Treat Nontuberculous Mycobacterial Infections

MmpL3 Inhibition: A New Approach to Treat Nontuberculous Mycobacterial Infections

Nanotechnology‐Based Targeted Drug Delivery: An Emerging Tool to Overcome Tuberculosis

Pks 13 inhibitors—a promising target for future antitubercular agents

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