DOI: 10.1101/463232Nov 5, 2018Paper

Characterization and elimination of stochastically generated persister subpopulation in mycobacteria

BioRxiv : the Preprint Server for Biology
V. SrinivasNitin S Baliga

Abstract

Mycobacterium tuberculosis (MTB) is able to persist in the host for long periods of time, even during antibiotic treatment. Eliminating persister cells, which are implicated as the primary reason for treatment failure, is essential for shortening TB treatment regimen. Here, we report a novel methodology, Per-Sort, to identify and sort miniscule numbers of translationally dormant mycobacterial cells within an isogenic mycobacterium population. Using Per-Sort we have discovered that translationally dormant cells pre-exist (under optimal growth conditions) as a fraction of a percent of isogenic mycobacterial cultures, suggesting they are generated stochastically as a bet hedging strategy. We show that this pre-existing translationally dormant subpopulation of cells are tolerant to antibiotics, small in size, low in oxidative metabolism, and expand in number upon nutrient starvation. Finally, through transcriptional profiling at single cell resolution, weve determined that the pre-existing persisters are a heterogeneous mix of vapC30, mazF, and relA/spoT overexpressing cells that are eliminated and sensitized to antibiotic killing through induction of respiration.\n\nHighlightsO_LIWe have developed a novel method, Per-Sort, to isol...Continue Reading

Software Mentioned

PerSort
PVclust
R
CellRox
PerSorted
ScanLag

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Antifungals

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.