LprG and <scp>PE</scp>_<scp>PGRS</scp>33 <i>Mycobacterium tuberculosis</i> virulence factors induce differential mitochondrial dynamics in macrophages

Aguilar-López, Bruno A.; Correa, Francisco; Altamirano, María Maximina B. Moreno; Espitia, Clara; Hernández-Longoria, Rocío; Oliva-Ramírez, Jacqueline; Padierna-Olivos, Juan; Sánchez‐García, Francisco Javier

doi:10.1111/sji.12728

Cited by 26 publications

(20 citation statements)

References 43 publications

(54 reference statements)

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“…Mtb Rv1411c (LprG/p27) induces mitochondrial fission and changes mitochondrial Ca 2+ dynamics and lowers the host rate of respiration (Path F, Figure 2 ). On the contrary, Rv1818c (PE_PGRS33) promotes mitochondrial fusion with no effect on Ca 2+ uptake and respiratory rate of the cell (Aguilar-López et al, 2019 ). Similar effects were observed upon infection with M. smegmatis overexpressing MAV2054 in bone marrow-derived macrophages.…”

Section: Mycobacterium Tuberculosis Infection Reallocates MImentioning

confidence: 99%

Mycobacterial Control of Host Mitochondria: Bioenergetic and Metabolic Changes Shaping Cell Fate and Infection Outcome

Mohareer

Medikonda

Vadankula

et al. 2020

Front. Cell. Infect. Microbiol.

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Mitochondria, are undoubtedly critical organelle of a eukaryotic cell, which provide energy and offer a platform for most of the cellular signaling pathways that decide cell fate. The role of mitochondria in immune-metabolism is now emerging as a crucial process governing several pathological states, including infection, cancer, and diabetes. Mitochondria have therefore been a vulnerable target for several bacterial and viral pathogens to control host machinery for their survival, replication, and dissemination. Mycobacterium tuberculosis, a highly successful human pathogen, persists inside alveolar macrophages at the primary infection site, applying several strategies to circumvent macrophage defenses, including control of host mitochondria. The infection perse and specific mycobacterial factors that enter the host mitochondrial milieu perturb mitochondrial dynamics and function by disturbing mitochondrial membrane potential, shifting bioenergetics parameters such as ATP and ROS, orienting the host cell fate and thereby infection outcome. In the present review, we attempt to integrate the available information and emerging dogmas to get a holistic view of Mycobacterium tuberculosis infection visa -vis mycobacterial factors that target host mitochondria and changes therein in terms of morphology, dynamics, proteomic, and bioenergetic alterations that lead to a differential cell fate and immune response determining the disease outcome. We also discuss critical host factors and processes that are overturned by Mycobacterium tuberculosis, such as cAMP-mediated signaling, redox homeostasis, and lipid droplet formation. Further, we also present alternate dogmas as well as the gaps and limitations in understanding some of the present research areas, which can be further explored by understanding some critical processes during Mycobacterium tuberculosis infection and the reasons thereof. Toward the end, we propose to have a set of guidelines for pursuing investigations to maintain uniformity in terms of early and late phase, MOI of infection, infection duration and incubation periods, the strain of mycobacteria, passage numbers, and so on, which all work as probable variables toward different readouts. Such a setup would, therefore, help in the smooth integration of information across laboratories toward a better understanding of the disease and possibilities of host-directed therapy.

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Section: Mycobacterium Tuberculosis Infection Reallocates MImentioning

confidence: 99%

Mycobacterial Control of Host Mitochondria: Bioenergetic and Metabolic Changes Shaping Cell Fate and Infection Outcome

Mohareer

Medikonda

Vadankula

et al. 2020

Front. Cell. Infect. Microbiol.

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“…It has been proved that LprG involved in triacylglyceride levels, growth rate, and virulence regulation (35). Its implication in mycobacterium virulence has been appeared through the induction of mitochondrial ssion, interference with complex I and complex II respiration, and modi cation of mitochondrial calcium uptake, which in turn proposing that LprG-stimulated cells are in a lower bioenergetics state, which could support its immunosuppressive capacity in infection (36). The identi cation of LprG protein in M. tuberculosis was previously con rmed as P27 in the Mycobacterium tuberculosis complex and its gene is conserved across several pathogenic and nonpathogenic Mycobacterium species (37).…”

Section: Discussionmentioning

confidence: 99%

Differential Protein Expression in Exponential and Stationary Growth Phases of Mycobacterium avium subsp. hominissuis 104

Enany

Ato

Matsumoto

2020

Preprint

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Background:Mycobacterium avium complex (MAC) is the most common non-tuberculous mycobacteria (NTM) causing different types of pulmonary diseases. Although, genomic and transcriptomic analysis of Mycobacterium avium 104 (M. avium 104) have extensively done, little is known about the proteomics of M. avium 104. Methods:We utilized the proteomics technology to analyze the changes in the whole proteome of M. avium 104 during exponential and stationary growth phases. Results:We found 12 dys-regulated proteins; the up-regulated protein hits in the stationary phase were involved in aminopeptidase, choline dehydrogenase, oxidoreductase, and ATP binding, while, the down-regulated proteins in the stationary phase were acetyl-CoA acetyltransferase, universal stress protein, catalase peroxidase, and elongation factor (Tu). The differently expressed proteins between exponential and stationary phases were implicated in metabolism and stress response pointing to the functional adaptation of the cells to the environment. Conclusion:Proteomic analysis in different growth phases could participate in understanding the course of infection, the mechanisms of virulence, the means of survival, and the possible targets for treatment.

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“…The importance of mitochondrial dynamics during Mtb infection has been recently recognized (12)(13)(14)(15). However, its role in bactericidal activity and underlying mechanism remains uncertain.…”

Section: Discussionmentioning

confidence: 99%

“…However, how Mtb infection influences mitochondrial dynamics and the metabolic profile remains uncertain. A previous study found that different Mtb virulent factors altered differential mitochondrial dynamics in macrophages (12). Jamwal et al (2012) showed that, compared with an avirulent strain, a virulent strain of Mtb elongated the mitochondria and increased ATP levels in a human macrophage THP-1 cell line as a way to prevent host macrophage apoptosis (13).…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial fusion mediated by mitofusin 1 regulates macrophage mycobactericidal activity by enhancing autophagy

Ning

Cai

Dai

et al. 2020

Preprint

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Mitochondria as a highly dynamic organelle continuously changes morphology and position during its life cycle. Mitochondrial dynamics including fission and fusion play a critical role in maintaining functional mitochondria for ATP production, which is directly linked to host defense against Mtb infection. However, how macrophages regulate mitochondrial dynamics during Mycobacterium tuberculosis (Mtb) infection remains elusive. In this study, we found that Mtb infection induced mitochondrial fusion through enhancing the expression of mitofusin 1 (MFN1), which resulted in increased ATP production. Silencing MFN1 inhibited mitochondrial fusion and subsequently reduced ATP production, which, in turn, severely impaired macrophage mycobactericidal activity by inhibiting autophagy. Impairment of mycobactericidal activity and autophagy was replicated using oligomycin, an inhibitor of ATP synthase. In summary, our study revealed MFN1-mediated mitochondrial fusion is essential for macrophage mycobactericidal activity through the regulation of ATP dependent autophagy. MFN1-mediated metabolism pathway might be targets for development of host direct therapy (HDT) strategy against TB.

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LprG and PE_PGRS33 Mycobacterium tuberculosis virulence factors induce differential mitochondrial dynamics in macrophages

Cited by 26 publications

References 43 publications

Mycobacterial Control of Host Mitochondria: Bioenergetic and Metabolic Changes Shaping Cell Fate and Infection Outcome

Mycobacterial Control of Host Mitochondria: Bioenergetic and Metabolic Changes Shaping Cell Fate and Infection Outcome

Differential Protein Expression in Exponential and Stationary Growth Phases of Mycobacterium avium subsp. hominissuis 104

Mitochondrial fusion mediated by mitofusin 1 regulates macrophage mycobactericidal activity by enhancing autophagy

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