Advances in host‐based screening for compounds with intracellular anti‐mycobacterial activity. (13th May 2021)

• Record Type: Journal Article
• Authors: Subhash, Neeraja; Sundaramurthy, Varadharajan
• Other Names: Hartland Elizabeth guestEditor.
• Is Part Of: Cellular microbiology. Volume 23:Number 7(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-05-13
• Subjects: antimicrobial -- host‐based chemical screen -- infection -- microbial‐cell interaction -- mycobacteria -- tuberculosis; Microbiology -- Periodicals; Cytology -- Periodicals; Host-parasite relationships -- Periodicals; Microbiology -- Periodicals; Cells -- Periodicals; Microbiologie -- Périodiques; Microbiologie; Relation hôte-parasite; Cytologie; Cellule; Réponse cellulaire; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); 579.05
• DOI: 10.1111/cmi.13337
• Languages: English
• ISSNs: 1462-5814

Abstract

Abstract: Intracellular pathogens interact with host systems in intimate ways to sustain a pathogenic lifestyle. Consequently, these interactions can potentially be targets of host‐directed interventions against infectious diseases. In case of tuberculosis (TB), caused by the bacterium Mycobacterium tuberculosis ( Mtb ), while effective anti‐tubercular compounds are available, the long treatment duration and emerging drug resistance necessitate identification of new class of molecules with anti‐TB activity, as well as new treatment strategies. A significant part of the effort in finding new anti‐TB drugs is focused on bacterial targets in bacterial systems. However, the host environment plays a major role in pathogenesis mechanisms and must be considered actively in these efforts. On the one hand, the bacterial origin targets must be relevant and accessible in the host, while on the other hand, new host origin targets required for the bacterial survival can be targeted. Such targets are good candidates for host‐directed therapeutics, a strategy gaining traction as an adjunct in TB treatment. In this review, we will summarise the screening platforms used to identify compounds with anti‐tubercular activities inside different host environments and outline recent technical advances in these platforms. Finally, while the examples given are specific to mycobacteria, the methods and principles outlined are broadly applicable to most intracellular infections. Abstract : Host based systems are disease relevant platforms for screening anti Mtb compounds. New target and chemical spaces open up for drug discovery in these platforms while recent advances enable sensitive detection and identification of subtle phenotypes. This review provides an overview of these advances and the recent host based chemical screens for identification of anti‐ Mtb compounds.