Awakening sleeper cells: a narrative review on bacterial magic spot synthetases as potential drug targets to overcome persistence

Veetilvalappil, Vimal Venu and Mathew, Jesil Aranjani and Joseph, Alex (2022) Awakening sleeper cells: a narrative review on bacterial magic spot synthetases as potential drug targets to overcome persistence. Current Genetics, 68. pp. 49-60. ISSN 0172-8083

[img] PDF
14794.pdf - Published Version
Restricted to Registered users only

Download (1MB) | Request a copy

Abstract

Magic spot synthetases are emerging targets to overcome persistence caused by stringent response. The 'stringent response' is a bacterial stress survival mechanism, which results in the accumulation of alarmones (also called Magic spots) leading to the formation of dormant persister cells. These 'sleeper cells' evade antibiotic treatment and could result in relapse of infection. This review broadly investigates the phenomenon of stringent response and persistence, and specifically discusses the distribution, classification, and nomenclature of proteins such as Rel/SpoT homologs (RSH), responsible for alarmone synthesis. The authors further explain the relevance of RSH as potential drug targets to break the dormancy of persister cells commonly seen in biofilms. One of the significant factors that initiate alarmone synthesis is nutrient deficiency. In a starved condition, ribosome-associated RSH detects deacylated tRNA and initiates alarmone synthesis. Accumulation of alarmones has a considerable effect on bacterial physiology, virulence, biofilm formation, and persister cell formation. Preventing alarmone synthesis by inhibiting RSH responsible for alarmone synthesis will prevent or reduce persister cells' formation. Magic spot synthetases are thus potential targets that could be explored to overcome persistence seen in biofilms

Item Type: Article
Uncontrolled Keywords: Alarmone synthesis; Bacterial magic spots; Rel/SpoT homologs; Stringent response; Bacterial stress survival mechanism; Wake persister cells
Subjects: Pharmacy > MCOPS Manipal > Pharmaceutical Biotechnology
Pharmacy > MCOPS Manipal > Pharmaceutical Chemistry
Depositing User: KMC Library
Date Deposited: 02 Mar 2022 03:42
Last Modified: 02 Mar 2022 03:42
URI: http://eprints.manipal.edu/id/eprint/158372

Actions (login required)

View Item View Item