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Review

Biosynthesis of Galactan in Mycobacterium tuberculosis as a Viable TB Drug Target?

1
Department of Biochemistry, Faculty of Natural Sciences, Comenius University in Bratislava, Mlynská Dolina, Ilkovičova 6, 84215 Bratislava, Slovakia
2
Institute of Chemistry, Slovak Academy of Sciences, Dúbravská Cesta 9, 84538 Bratislava, Slovakia
*
Author to whom correspondence should be addressed.
Received: 17 December 2019 / Revised: 27 December 2019 / Accepted: 2 January 2020 / Published: 6 January 2020
(This article belongs to the Special Issue Antibiotics against Tuberculosis)
While target-based drug design has proved successful in several therapeutic areas, this approach has not yet provided compelling outcomes in the field of antibacterial agents. This statement remains especially true for the development of novel therapeutic interventions against tuberculosis, an infectious disease that is among the top ten leading causes of death globally. Mycobacterial galactan is an important component of the protective cell wall core of the tuberculosis pathogen and it could provide a promising target for the design of new drugs. In this review, we summarize the current knowledge on galactan biosynthesis in Mycobacterium tuberculosis, including landmark findings that led to the discovery and understanding of three key enzymes in this pathway: UDP-galactose mutase, and galactofuranosyl transferases GlfT1 and GlfT2. Moreover, we recapitulate the efforts aimed at their inhibition. The predicted common transition states of the three enzymes provide the lucrative possibility of multitargeting in pharmaceutical development, a favourable property in the mitigation of drug resistance. We believe that a tight interplay between target-based computational approaches and experimental methods will result in the development of original inhibitors that could serve as the basis of a new generation of drugs against tuberculosis. View Full-Text
Keywords: UDP-galactose mutase; galactofuranosyl transferase; GlfT1; GlfT2; cell wall; drug design UDP-galactose mutase; galactofuranosyl transferase; GlfT1; GlfT2; cell wall; drug design
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MDPI and ACS Style

Konyariková, Z.; Savková, K.; Kozmon, S.; Mikušová, K. Biosynthesis of Galactan in Mycobacterium tuberculosis as a Viable TB Drug Target? Antibiotics 2020, 9, 20. https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9010020

AMA Style

Konyariková Z, Savková K, Kozmon S, Mikušová K. Biosynthesis of Galactan in Mycobacterium tuberculosis as a Viable TB Drug Target? Antibiotics. 2020; 9(1):20. https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9010020

Chicago/Turabian Style

Konyariková, Zuzana, Karin Savková, Stanislav Kozmon, and Katarína Mikušová. 2020. "Biosynthesis of Galactan in Mycobacterium tuberculosis as a Viable TB Drug Target?" Antibiotics 9, no. 1: 20. https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9010020

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