Apr 30, 2020

PerSort facilitates characterization and elimination of persister subpopulation in mycobacteria

BioRxiv : the Preprint Server for Biology
Vivek SrinivasNitin Baliga

Abstract

Mycobacterium tuberculosis (MTB) generates phenotypic diversity to persist and survive the harsh conditions encountered during infection. MTB avoids immune effectors and antibacterial killing by entering into distinct physiological states. The surviving cells, persisters, are a major barrier to the timely and relapse-free treatment of tuberculosis (TB). We present for the first time, PerSort, a method to isolate and characterize persisters in the absence of antibiotic, or other, pressure. We demonstrate the value of PerSort to isolate translationally dormant cells that pre-exist in small numbers within Mycobacterium spp. cultures growing under optimal conditions, but which dramatically increased in proportion under stress conditions. The translationally dormant subpopulation exhibited multidrug tolerance and regrowth properties consistent with persister cells. Furthermore, PerSort enabled single-cell transcriptional profiling that provided evidence that the translationally dormant persisters were generated through a variety of mechanisms, including vapC30, mazF, and relA/spoT overexpression. Finally, we demonstrate that notwithstanding the varied mechanisms by which the persister cells were generated, they converge on a similar...Continue Reading

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Mentioned in this Paper

Treatment Protocols
Size
RELA wt Allele
Tuberculosis
Antibiotic throat preparations
Transcription, Genetic
Antifungal Antibiotics, Topical
Cell Respiration
Antibiotics, Gynecological
NF-kappaB p50/p65 Complex

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