Deoxyribonucleic acid replication time in Mycobacterium tuberculosis H37 Rv

Hiriyanna, KT; Ramakrishnan, T. V.

doi:10.1007/bf00414718

Cited by 56 publications

(42 citation statements)

References 14 publications

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“…The real-time single-cell analysis presented here reveals some unusual features of the mycobacterial cell cycle that could not have been uncovered by population-based measurements. For example, a previous population-based study reported that the average duration of the C period in M. smegmatis is B110 min in batch cultures growing with a population doubling time of B180 min 35 . The fact that the average C period duration is less than the average interdivision time suggests a canonical organization of the mycobacterial cell cycle with discrete B, C and D periods 25 .…”

Section: Discussionmentioning

confidence: 99%

Single-cell dynamics of the chromosome replication and cell division cycles in mycobacteria

et al. 2013

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During the bacterial cell cycle, chromosome replication and cell division must be coordinated with overall cell growth in order to maintain the correct ploidy and cell size. The spatial and temporal coordination of these processes in mycobacteria is not understood. Here we use microfluidics and time-lapse fluorescence microscopy to measure the dynamics of cell growth, division and chromosome replication in single cells of Mycobacterium smegmatis. We find that single-cell growth is size-dependent (large cells grow faster than small cells), which implicates a size-control mechanism in cell-size homoeostasis. Asymmetric division of mother cells gives rise to unequally sized sibling cells that grow at different velocities but show no differential sensitivity to antibiotics. Individual cells are restricted to one round of chromosome replication per cell division cycle, although replication usually initiates in the mother cell before cytokinesis and terminates in the daughter cells after cytokinesis. These studies reveal important differences between cell cycle organization in mycobacteria compared with better-studied model organisms.

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Section: Discussionmentioning

confidence: 99%

Single-cell dynamics of the chromosome replication and cell division cycles in mycobacteria

et al. 2013

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“…NER has been implicated in the virulence of M. tuberculosis in mice (13) through the processing of DNA damage caused by nitrosative stress (12). Given the comparatively low rate of DNA replication in M. tuberculosis (24), NER may play an even more dominant role than damage tolerance in enabling this organism to contend with such lesions.…”

Section: Discussionmentioning

confidence: 99%

Role of the DinB Homologs Rv1537 and Rv3056 in Mycobacterium tuberculosis

et al. 2010

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The environment encountered by Mycobacterium tuberculosis during infection is genotoxic. Most bacteria tolerate DNA damage by engaging specialized DNA polymerases that catalyze translesion synthesis (TLS) across sites of damage. M. tuberculosis possesses two putative members of the DinB class of Y-family DNA polymerases, DinB1 (Rv1537) and DinB2 (Rv3056); however, their role in damage tolerance, mutagenesis, and survival is unknown. Here, both dinB1 and dinB2 are shown to be expressed in vitro in a growth phasedependent manner, with dinB2 levels 12-to 40-fold higher than those of dinB1. Yeast two-hybrid analyses revealed that DinB1, but not DinB2, interacts with the ␤-clamp, consistent with its canonical C-terminal ␤-binding motif. However, knockout of dinB1, dinB2, or both had no effect on the susceptibility of M. tuberculosis to compounds that form N 2 -dG adducts and alkylating agents. Similarly, deletion of these genes individually or in combination did not affect the rate of spontaneous mutation to rifampin resistance or the spectrum of resistance-conferring rpoB mutations and had no impact on growth or survival in human or mouse macrophages or in mice. Moreover, neither gene conferred a mutator phenotype when expressed ectopically in Mycobacterium smegmatis. The lack of the effect of altering the complements or expression levels of dinB1 and/or dinB2 under conditions predicted to be phenotypically revealing suggests that the DinB homologs from M. tuberculosis do not behave like their counterparts from other organisms.The emergence and global spread of multi-and extensively drug-resistant strains of Mycobacterium tuberculosis have further complicated the already daunting challenge of controlling tuberculosis (TB) (15). The mechanisms that underlie the evolution of drug resistance in M. tuberculosis by chromosomal mutagenesis and their association with the conditions that tubercle bacilli encounter during the course of infection are poorly understood (6). It has been postulated that hypoxia, low pH, nutrient deprivation, and nitrosative and oxidative stress impose environmental and host immune-mediated DNA-damaging insults on infecting bacilli (64). In addition, the observed importance of excision repair pathways for the growth and survival of M. tuberculosis in murine models of infection (13, 55) and the upregulation of M. tuberculosis genes involved in DNA repair and modification in pulmonary TB in humans provide compelling evidence that the in vivo environment is DNA damaging (51).Damage tolerance constitutes an integral component of an organism's response to genotoxic stress, preventing collapse of the replication fork at persisting, replication-blocking lesions through the engagement of specialized DNA polymerases that are able to catalyze translesion synthesis (TLS) across the sites of damage (19,21,60). Most TLS polymerases belong to the Y family, which comprises a wide range of structurally related proteins present in bacteria, archaea, and eukaryotes (44). Of these, the DinB subfamily of Y family po...

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“…a The number of genomes per cell was calculated by use of the formula described in the text, using the values C ϭ 10.33 h and D ϭ 6 h (8,10,23).…”

Section: 07mentioning

confidence: 99%

Compiling a Molecular Inventory for Mycobacterium bovis BCG at Two Growth Rates: Evidence for Growth Rate-Mediated Regulation of Ribosome Biosynthesis and Lipid Metabolism

et al. 2005

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An experimental system of Mycobacterium tuberculosis growth in a carbon-limited chemostat has been established by the use of Mycobacterium bovis BCG as a model organism. For this model, carbon-limited chemostats with low concentrations of glycerol were used to simulate possible growth rates during different stages of tuberculosis. A doubling time of 23 h (D ‫؍‬ 0.03 h ؊1 ) was adopted to represent cells during the acute phase of infection, whereas a lower dilution rate equivalent to a doubling time of 69 h (D ‫؍‬ 0.01 h ؊1 ) was used to model mycobacterial persistence. This chemostat model allowed the specific response of the mycobacterial cell to carbon limitation at different growth rates to be elucidated. The macromolecular (RNA, DNA, carbohydrate, and lipid) and elemental (C, H, and N) compositions of the biomass were determined for steady-state cultures, revealing that carbohydrates and lipids comprised more than half of the dry mass of the BCG cell, with only a quarter of the dry weight consisting of protein and RNA. Consistent with studies of other bacteria, the specific growth rate impacts on the macromolecular content of BCG and the proportions of lipid, RNA, and protein increased significantly with the growth rate. The correlation of RNA content with the growth rate indicates that ribosome production in carbon-limited M. bovis BCG cells is subject to growth rate-dependent control. The results also clearly show that the proportion of lipids in the mycobacterial cell is very sensitive to changes in the growth rate, probably reflecting changes in the amounts of storage lipids. Finally, this study demonstrates the utility of the chemostat model of mycobacterial growth for functional genomic, physiology, and systems biology studies.With three million people dying from tuberculosis (TB) annually, Mycobacterium tuberculosis remains a formidable pathogen. Tuberculosis ranks among the top 10 causes of global mortality and morbidity and is the leading cause of infectious disease (66). The ability of M. tuberculosis to adapt to and survive harsh environmental conditions in order to establish and maintain long-term infections within its human host is fundamental to this organism's success. Modification of the mycobacterial cell in response to changes in the environment is crucial to this adaptive process, but detailed information about how M. tuberculosis changes its macromolecular composition in response to its environment and growth rate is lacking.The genome sequence of M. tuberculosis has been available since 1998 (9). Although information obtained from the genome sequence provided new and valuable insights into the biology of the tubercle bacillus, the genome itself provides few clues regarding how the pathogen responds to its environment by changing its cellular composition. One of the principal tasks of postgenomic biological studies of M. tuberculosis is to understand how the genome orchestrates the structure and dynamics of the cell in response to changes in the environment. This task requires an integrat...

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Deoxyribonucleic acid replication time in Mycobacterium tuberculosis H37 Rv

Cited by 56 publications

References 14 publications

Single-cell dynamics of the chromosome replication and cell division cycles in mycobacteria

Single-cell dynamics of the chromosome replication and cell division cycles in mycobacteria

Role of the DinB Homologs Rv1537 and Rv3056 in Mycobacterium tuberculosis

Compiling a Molecular Inventory for Mycobacterium bovis BCG at Two Growth Rates: Evidence for Growth Rate-Mediated Regulation of Ribosome Biosynthesis and Lipid Metabolism

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