Gene Regulatory Mechanism of Mycobacterium Tuberculosis during Dormancy

Liu, Yiduo; Li, Han; Dai, Dejia; He, Jiakang; Liang, Zhengmin

doi:10.3390/cimb46060348

CIMB

2024

DOI: 10.3390/cimb46060348

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Gene Regulatory Mechanism of Mycobacterium Tuberculosis during Dormancy

Yiduo Liu,

Han Li,

Dejia Dai

et al.

Abstract: Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) complex, is a zoonotic disease that remains one of the leading causes of death worldwide. Latent tuberculosis infection reactivation is a challenging obstacle to eradicating TB globally. Understanding the gene regulatory network of Mtb during dormancy is important. This review discusses up-to-date information about TB gene regulatory networks during dormancy, focusing on the regulation of lipid and energy metabolism, dormancy survival regulator (Dos… Show more

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2024

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Cited by 3 publications

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A comprehensive review on latent role of stress proteins in antibiotic resistance

Dalbanjan,

Kadapure,

S.K

2024

The Microbe

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A comprehensive review on latent role of stress proteins in antibiotic resistance

Dalbanjan,

Kadapure,

S.K

2024

The Microbe

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Bacterial Persister Cells and Development of Antibiotic Resistance in Chronic Infections: An Update

Kunnath,

Suodha Suoodh,

Chellappan

et al. 2024

Br J Biomed Sci

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The global issue of antimicrobial resistance poses significant challenges to public health. The World Health Organization (WHO) has highlighted it as a major global health threat, causing an estimated 700,000 deaths worldwide. Understanding the multifaceted nature of antibiotic resistance is crucial for developing effective strategies. Several physiological and biochemical mechanisms are involved in the development of antibiotic resistance. Bacterial cells may escape the bactericidal actions of the drugs by entering a physiologically dormant state known as bacterial persistence. Recent findings in this field suggest that bacterial persistence can be one of the main sources of chronic infections. The antibiotic tolerance developed by the persister cells could tolerate high levels of antibiotics and may give rise to persister offspring. These persister offspring could be attributed to antibiotic resistance mechanisms, especially in chronic infections. This review attempts to shed light on persister-induced antibiotic resistance and the current therapeutic strategies.

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Exploring the Genetic Landscape of Mycobacterium tuberculosis: Unlocking the Differences in Between Latent and Active Tuberculosis

Velayati,

Mitaria,

Farnia

et al. 2024

The International Journal of Mycobacteriology

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Background: Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), can enter a dormant phase within host tissues, complicating treatment and highlighting the need to investigate the genetic changes associated with dormancy. Methods: This study examined clinical isolates of MTB, representing a range of susceptibility profiles and standard reference laboratory strains, i.e., H37Rv and Mycobacterium bovis bacillus Calmette–Guérin. Each strain was subcultured in a controlled laboratory environment to analyze two distinct phases: one maintained in vitro under a double-stress dormancy model using the Wayne model (characterized by the absence of oxygen and nutrients) for 12 months, and the other examined during its exponential growth phase. Whole-genome sequencing and protein structure analysis using bioinformatics tools were performed to characterize and compare mutations in isolates at each phase. Results: Three distinct frameshift mutations were identified in the fbiC, PPE35, and ald genes, and one upstream mutation in whiB6 genes in all studied isolates under dormancy, irrespective of their susceptibility patterns (P < 0.01). Among drug-resistant strains, at the exponential phase isolated from patients with prolonged treatment, 5%–7% had PPE35, ald mutations, whereas 95% had the whiB6 mutation, suggesting that adaptive stress responses may be triggered under in vivo conditions. Conclusions: The newly identified frameshift mutations (fbiC, PPE35, and ald genes), consistently found in both laboratory and clinical isolates, seem to play a critical role in the survival of MTB during dormancy. Based on these findings, designing a molecular test to differentiate between active and latent TB possibly enables timely prophylactic interventions.

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Gene Regulatory Mechanism of Mycobacterium Tuberculosis during Dormancy

Cited by 3 publications

References 189 publications

A comprehensive review on latent role of stress proteins in antibiotic resistance

A comprehensive review on latent role of stress proteins in antibiotic resistance

Bacterial Persister Cells and Development of Antibiotic Resistance in Chronic Infections: An Update

Exploring the Genetic Landscape of Mycobacterium tuberculosis: Unlocking the Differences in Between Latent and Active Tuberculosis

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