The role of Mycobacterium tuberculosis acetyltransferase and protein acetylation modifications in tuberculosis

Huang, Yinxia; Zhu, Chuanzhi; Pan, Liping; Zhang, Zongde

doi:10.3389/fcimb.2023.1218583

Cited by 2 publications

(1 citation statement)

References 153 publications

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“…Targeting the transport of glycolipids such as TMM to the cell envelope may aid in weakening the cell envelope and possibly increase the efficacy of other anti-TB drugs. Further, the acetylation of M.tb proteins plays a critical mechanism of bacterial adaptation to changing environments, being implicated in virulence, drug resistance, regulation of metabolism, and host anti-TB immune responses (Sun et al, 2022;Huang et al, 2023). It is plausible that increased acylation of M.tb cell envelope trehalose-containing lipids could be play a similar role (Sun et al, 2022).…”

Section: Trehalose-containing Glycolipidsmentioning

confidence: 99%

Drug-resistant strains of Mycobacterium tuberculosis: cell envelope profiles and interactions with the host

Schami,

Islam,

Belisle

et al. 2023

Front. Cell. Infect. Microbiol.

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In the past few decades, drug-resistant (DR) strains of Mycobacterium tuberculosis (M.tb), the causative agent of tuberculosis (TB), have become increasingly prevalent and pose a threat to worldwide public health. These strains range from multi (MDR) to extensively (XDR) drug-resistant, making them very difficult to treat. Further, the current and future impact of the Coronavirus Disease 2019 (COVID-19) pandemic on the development of DR-TB is still unknown. Although exhaustive studies have been conducted depicting the uniqueness of the M.tb cell envelope, little is known about how its composition changes in relation to drug resistance acquisition. This knowledge is critical to understanding the capacity of DR-M.tb strains to resist anti-TB drugs, and to inform us on the future design of anti-TB drugs to combat these difficult-to-treat strains. In this review, we discuss the complexities of the M.tb cell envelope along with recent studies investigating how M.tb structurally and biochemically changes in relation to drug resistance. Further, we will describe what is currently known about the influence of M.tb drug resistance on infection outcomes, focusing on its impact on fitness, persister-bacteria, and subclinical TB.

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Section: Trehalose-containing Glycolipidsmentioning

confidence: 99%

Drug-resistant strains of Mycobacterium tuberculosis: cell envelope profiles and interactions with the host

Schami,

Islam,

Belisle

et al. 2023

Front. Cell. Infect. Microbiol.

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Quantitative analysis of the lysine acetylome reveals the role of SIRT3-mediated HSP60 deacetylation in suppressing intracellular Mycobacterium tuberculosis survival

Zhu,

Duan,

Dong

et al. 2024

Microbiol Spectr

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Protein acetylation and deacetylation are key epigenetic modifications that regulate the initiation and development of several diseases. In the context of infection with Mycobacterium tuberculosis ( M. tb ), these processes are essential for host–pathogen interactions and immune responses. However, the specific effects of acetylation and deacetylation on cellular functions during M. tb infection are not fully understood. This study employed Tandem Mass Tag (TMT) labeling for quantitative proteomic profiling to examine the acetylproteome (acetylome) profiles of noninfected and M. tb -infected macrophages. We identified 715 acetylated peptides from 1,072 proteins and quantified 544 lysine acetylation sites (Kac) in 402 proteins in noninfected and M. tb -infected macrophages. Our research revealed a link between acetylation events and metabolic changes during M. tb infection. Notably, the deacetylation of heat shock protein 60 (HSP60), a key chaperone protein, was significantly associated with this process. Specifically, the deacetylation of HSP60 at K96 by sirtuin3 (SIRT3) enhances macrophage apoptosis, leading to the elimination of intracellular M. tb . These findings underscore the pivotal role of the SIRT3–HSP60 axis in the host immune response to M. tb . This study offers a new perspective on host protein acetylation and suggests that targeting host-directed therapies could be a promising approach for tuberculosis immunotherapy. IMPORTANCE Protein acetylation is crucial for the onset, development, and outcome of tuberculosis (TB). Our study comprehensively investigated the dynamics of lysine acetylation during M. tb infection, shedding light on the intricate host–pathogen interactions that underlie the pathogenesis of tuberculosis. Using an advanced quantitative lysine proteomics approach, different profiles of acetylation sites and proteins in macrophages infected with M. tb were identified. Functional enrichment and protein–protein network analyses revealed significant associations between acetylated proteins and key cellular pathways, highlighting their critical role in the host response to M. tb infection. Furthermore, the deacetylation of HSP60 and its influence on macrophage-mediated clearance of M. tb underscore the functional significance of acetylation in tuberculosis pathogenesis. In conclusion, this study provides valuable insights into the regulatory mechanisms governing host immune responses to M. tb infection and offers promising avenues for developing novel therapeutic interventions against TB.

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The role of Mycobacterium tuberculosis acetyltransferase and protein acetylation modifications in tuberculosis

Cited by 2 publications

References 153 publications

Drug-resistant strains of Mycobacterium tuberculosis: cell envelope profiles and interactions with the host

Drug-resistant strains of Mycobacterium tuberculosis: cell envelope profiles and interactions with the host

Quantitative analysis of the lysine acetylome reveals the role of SIRT3-mediated HSP60 deacetylation in suppressing intracellular Mycobacterium tuberculosis survival

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