The diacylglycerol acyltransferase Rv3371 of Mycobacterium tuberculosis is required for growth arrest and involved in stress-induced cell wall alterations

Rastogi, Shivangi; Singh, Amit Kumar; Chandra, Gyan; Kushwaha, Pragati; Pant, Garima; Singh, Kavita; Mitra, Kalyan; Sashidhara, Koneni V.; Krishnan, Manju Y.

doi:10.1016/j.tube.2017.02.001

Cited by 12 publications

(13 citation statements)

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“…Cell envelope modifications and enhanced antibiotic susceptibility in M. smegmatis have been observed under iron deficiency ( Pal et al, 2015 ). Triacylglycerol is also a component of M. tuberculosis cell envelope and loss of acid fastness is observed under iron deficiency and in hypoxia ( Rastogi et al, 2017 ). Such cell envelope modifications accompany non-replicative persistence and antibiotic tolerance of M. tuberculosis in vitro ( Rastogi et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

“…Triacylglycerol is also a component of M. tuberculosis cell envelope and loss of acid fastness is observed under iron deficiency and in hypoxia ( Rastogi et al, 2017 ). Such cell envelope modifications accompany non-replicative persistence and antibiotic tolerance of M. tuberculosis in vitro ( Rastogi et al, 2017 ). These observations indicate the influence of host factors on cellular adaptations in M. tuberculosis and antibiotic susceptibility.…”

Section: Discussionmentioning

confidence: 99%

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Ultrastructural Analysis of Cell Envelope and Accumulation of Lipid Inclusions in Clinical Mycobacterium tuberculosis Isolates from Sputum, Oxidative Stress, and Iron Deficiency

et al. 2018

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Introduction: Mycobacteria have several unique cellular characteristics, such as multiple cell envelope layers, elongation at cell poles, asymmetric cell division, and accumulation of intracytoplasmic lipid inclusions, which contributes to their survival under stress conditions. However, the understanding of these characteristics in clinical Mycobacterium tuberculosis (M. tuberculosis) isolates and under host stress is limited. We previously reported the influence of host stress on the cell length distribution in a large set of clinical M. tuberculosis isolates (n = 158). Here, we investigate the influence of host stress on the cellular ultrastructure of few clinical M. tuberculosis isolates (n = 8) from that study. The purpose of this study is to further understand the influence of host stress on the cellular adaptations of clinical M. tuberculosis isolates.Methods: We selected few M. tuberculosis isolates (n = 8) for analyzing the cellular ultrastructure ex vivo in sputum and under in vitro stress conditions by transmission electron microscopy. The cellular adaptations of M. tuberculosis in sputum were correlated with the ultrastructure of antibiotic sensitive and resistant isolates in liquid culture, under oxidative stress, iron deficiency, and exposure to isoniazid.Results: In sputum, M. tuberculosis accumulated intracytoplasmic lipid inclusions. In liquid culture, clinical M. tuberculosis revealed isolate to isolate variation in the extent of intracytoplasmic lipid inclusions, which were absent in the laboratory strain H37Rv. Oxidative stress, iron deficiency, and exposure to isoniazid increased the accumulation of lipid inclusions and decreased the thickness of the cell envelope electron transparent layer in M. tuberculosis cells. Furthermore, intracytoplasmic compartments were observed in iron deficient cells.Conclusion: Our ultrastructural analysis has revealed significant influence of host stress on the cellular adaptations in clinical M. tuberculosis isolates. These adaptations may contribute to the survival of M. tuberculosis under host and antibiotic stress conditions. Variation in the cellular adaptations among clinical M. tuberculosis isolates may correlate with their ability to persist in tuberculosis patients during antibiotic treatment. These observations indicate the need for further analyzing these cellular adaptations in a large set of clinical M. tuberculosis isolates. This will help to determine the significance of these cellular adaptations in the tuberculosis treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Ultrastructural Analysis of Cell Envelope and Accumulation of Lipid Inclusions in Clinical Mycobacterium tuberculosis Isolates from Sputum, Oxidative Stress, and Iron Deficiency

et al. 2018

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“…Mycobactin containing microvescicles secreted by Mtb grown in low iron medium were enriched in DAG and TAG as well as phosphatidylethanolamines (Prados-Rosales et al, 2014). We have reported decreased release of nile red staining microvesicles from a deletion mutant of Rv3371 , a possible tgs , grown in low iron medium (Rastogi et al, 2017). An increased accumulation of DAG and TAG in the mycomembrane could occur prior to budding of microvesicles, which are induced by low iron and other yet unidentified conditions.…”

Section: Biosynthesis Of Tag In Mycobacteriamentioning

confidence: 98%

“…Two of the putative Tgs- Rv3087 and Rv3371 were found essential for in vivo growth of H37Rv in C57BL/6J mouse spleen, by transposon site hybridization (Sassetti and Rubin, 2003). We have reported that an unmarked deletion mutant of Rv3371 continued replication and thus failed to enter persistence under in vitro hypoxia, low iron or nitrosative stress (Rastogi et al, 2017). Moreover, transposon mutants of tgs1 and Rv3371 were among the “over-represented” mutants under low oxygen environment, which suggested their inability to arrest cell division (Baek et al, 2011).…”

Section: Biosynthesis Of Tag In Mycobacteriamentioning

confidence: 99%

“…Likewise, the Tgs proteins of M. abscessus have been found exclusively in cell wall and cell membrane fractions (Viljoen et al, 2016). In addition to the predominant presence in the cell membrane fraction, minor amounts of Tgs proteins have been found in cytosolic fraction (Stöveken et al, 2005; Rastogi et al, 2017). Since these proteins do not have transmembrane domain, their membrane localization is thought to be mediated by ionic or hydrophobic interactions.…”

Section: Biosynthesis Of Tag In Mycobacteriamentioning

confidence: 99%

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Triacylglycerols: Fuelling the Hibernating Mycobacterium tuberculosis

Maurya

Bharti

Krishnan

2019

Front. Cell. Infect. Microbiol.

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Mycobacterium tuberculosis (Mtb) has the remarkable ability to persist with a modified metabolic status and phenotypic drug tolerance for long periods in the host without producing symptoms of active tuberculosis. These persisters may reactivate to cause active disease when the immune system becomes disrupted or compromised. Thus, the infected hosts with the persisters serve as natural reservoir of the deadly pathogen. Understanding the host and bacterial factors contributing to Mtb persistence is important to devise strategies to tackle the Mtb persisters. Host lipids act as the major source of carbon and energy for Mtb. Fatty acids derived from the host cells are converted to triacylglycerols (triglycerides or TAG) and stored in the bacterial cytoplasm. TAG serves as a dependable, long-term energy source of lesser molecular mass than other storage molecules like glycogen. TAG are found in substantial amounts in the mycobacterial cell wall. This review discusses the production, accumulation and possible roles of TAG in mycobacteria, pointing out the aspects that remain to be explored. Finally, the essentiality of TAG synthesis for Mtb is discussed with implications for identification of intervention strategies.

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Mycobacterial Lipid Bodies and the Chemosensitivity and Transmission of Tuberculosis

Garton,

Barer

2020

Health Consequences of Microbial Interactions With Hydrocarbons, Oils, and Lipids

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The diacylglycerol acyltransferase Rv3371 of Mycobacterium tuberculosis is required for growth arrest and involved in stress-induced cell wall alterations

Cited by 12 publications

References 49 publications

Ultrastructural Analysis of Cell Envelope and Accumulation of Lipid Inclusions in Clinical Mycobacterium tuberculosis Isolates from Sputum, Oxidative Stress, and Iron Deficiency

Ultrastructural Analysis of Cell Envelope and Accumulation of Lipid Inclusions in Clinical Mycobacterium tuberculosis Isolates from Sputum, Oxidative Stress, and Iron Deficiency

Triacylglycerols: Fuelling the Hibernating Mycobacterium tuberculosis

Mycobacterial Lipid Bodies and the Chemosensitivity and Transmission of Tuberculosis

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