Dormant ovoid cells of Mycobacterium tuberculosis are formed in response to gradual external acidification

Shleeva, Margarita O.; Kudykina, Yulia K.; Vostroknutova, G. N.; Suzina, N. E.; Mulyukin, A. L.; Kaprelyants, Arseny S.

doi:10.1016/j.tube.2010.12.006

Cited by 110 publications

(110 citation statements)

References 47 publications

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“…Other reported in vitro models for producing DD Mtb include hypoxia and starvation with antibiotic exposure (19), potassium depletion (41), exposure of log-phase cells to antibiotics (42), and gradual acidification (43). It is not clear why we did not succeed in producing DD Mtb with methods like these.…”

Section: Discussionmentioning

confidence: 94%

Rifamycin action on RNA polymerase in antibiotic-tolerant Mycobacterium tuberculosis results in differentially detectable populations

Saito

Warrier

Somersan-Karakaya

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

107

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Mycobacterium tuberculosis (Mtb) encounters stresses during the pathogenesis and treatment of tuberculosis (TB) that can suppress replication of the bacteria and render them phenotypically tolerant to most available drugs. Where studied, the majority of Mtb in the sputum of most untreated subjects with active TB have been found to be nonreplicating by the criterion that they do not grow as colony-forming units (cfus) when plated on agar. However, these cells are viable because they grow when diluted in liquid media. A method for generating such "differentially detectable" (DD) Mtb in vitro would aid studies of the biology and drug susceptibility of this population, but lack of independent confirmation of reported methods has contributed to skepticism about their existence. Here, we identified confounding artifacts that, when avoided, allowed development of a reliable method of producing cultures of ≥90% DD Mtb in starved cells. We then characterized several drugs according to whether they contribute to the generation of DD Mtb or kill them. Of the agents tested, rifamycins led to DD Mtb generation, an effect lacking in a rifampin-resistant strain with a mutation in rpoB, which encodes the canonical rifampin target, the β subunit of RNA polymerase. In contrast, thioridazine did not generate DD Mtb from starved cells but killed those generated by rifampin.Mycobacterium tuberculosis | differentially detectable | phenotypic tolerance | rifampin | thioridazine

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Section: Discussionmentioning

confidence: 94%

Rifamycin action on RNA polymerase in antibiotic-tolerant Mycobacterium tuberculosis results in differentially detectable populations

Saito

Warrier

Somersan-Karakaya

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

107

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“…tuberculosis is known to exhibit extreme pleomorphism in certain circumstances. Various morphological forms of mycobacteria were observed by many authors and were described as "mycococcus form" (Csillag, 1964), large "amoeba-like cells" (Imaeda, 1975), giant noncellular structures or so called "budding yeast-like structures" (Koch, 2003), "elementary bodies and filament structures" (Merkal et al, 1973) "endospores" (Ghosh et al,2009;Traag et al, 2010) and "ovoid cells" ( Shleeva et al, 2011). Mycobacteria are unique among procaryotes with their cell wall structure, containing tightly packed mycolic acids that provide TB bacilli with efficient protection and remarkable capacity to resist to various exogenous stress conditions.…”

Section: L-conversion Morphology and Ultrastructurementioning

confidence: 99%

Cell Wall Deficiency in Mycobacteria: Latency and Persistence

Маркова¹

2012

Understanding Tuberculosis - Deciphering the Secret Life of the Bacilli

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“…In vitro Rpf-dependency can be induced by prolonged stationary growth phase culture, exposure to anti-tuberculous drugs, and gradual external acidification of culture media (Loraine et al, 2016;Mukamolova et al, 2002;Shleeva et al, 2011). Rpf-dependent mycobacteria are also generated in vivo, however the in vivo triggers for Rpf-dependency are as yet unresolved (Hu et al, 2015;Mukamolova et al, 2010;Turapov et al, 2014).…”

Section: Rpf-dependency Phenomenonmentioning

confidence: 99%

Resuscitation-promoting factors are important determinants of the pathophysiology inMycobacterium tuberculosisinfection

Rosser

Stover

Pareek

et al. 2017

Critical Reviews in Microbiology

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Resuscitation promoting factors (Rpf) are peptidoglycan-hydrolyzing enzymes that are pivotal in the resuscitation of quiescent actinobacteria including Mycobacterium tuberculosis. From the published data, it is clear that Rpf are required for the resuscitation of non-replicating bacilli and pathogenesis in murine infection model of tuberculosis, although their direct influence on human Mycobacterium tuberculosis infection is ill-defined. In this review, we describe the progress in the understanding of the roles that Rpf play in human tuberculosis pathogenesis and importance of bacilli dependent upon Rpf for growth for the outcome of human tuberculosis. We outline how this research is opening up important opportunities for the diagnosis, treatment and prevention of human disease, progress in which is essential to attain the ultimate goal of tuberculosis eradication.ARTICLE HISTORY

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Dormant ovoid cells of Mycobacterium tuberculosis are formed in response to gradual external acidification

Cited by 110 publications

References 47 publications

Rifamycin action on RNA polymerase in antibiotic-tolerant Mycobacterium tuberculosis results in differentially detectable populations

Rifamycin action on RNA polymerase in antibiotic-tolerant Mycobacterium tuberculosis results in differentially detectable populations

Cell Wall Deficiency in Mycobacteria: Latency and Persistence

Resuscitation-promoting factors are important determinants of the pathophysiology inMycobacterium tuberculosisinfection

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