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Review
. 2021 Oct 7:12:744167.
doi: 10.3389/fmicb.2021.744167. eCollection 2021.

Targeting the Mycobacterium tuberculosis Stringent Response as a Strategy for Shortening Tuberculosis Treatment

Carina Danchik  1 , Siqing Wang  1 , Petros C Karakousis  1
Affiliations
Review

Targeting the Mycobacterium tuberculosis Stringent Response as a Strategy for Shortening Tuberculosis Treatment

Carina Danchik et al. Front Microbiol. .

Abstract

The stringent response is well conserved across bacterial species and is a key pathway involved both in bacterial survival and virulence and in the induction of antibiotic tolerance in Mycobacteria. It is mediated by the alarmone (p)ppGpp and the regulatory molecule inorganic polyphosphate in response to stress conditions such as nutrient starvation. Efforts to pharmacologically target various components of the stringent response have shown promise in modulating mycobacterial virulence and antibiotic tolerance. In this review, we summarize the current understanding of the stringent response and its role in virulence and tolerance in Mycobacteria, including evidence that targeting this pathway could have therapeutic benefit.

Keywords: (p)ppGpp; Mycobacterium tuberculosis; antibiotic tolerance; hyperphosphorylated guanosine; inorganic polyphosphate; small molecule inhibitor; stringent response; vaccination.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Activity and regulation of key bacterial stringent response factors.
See this image and copyright information in PMC

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