ClpB is an essential stress regulator of Mycobacterium tuberculosis and endows survival advantage to dormant bacilli
| Autor: | Sujata Kumari, Prajna Tripathi, Janendra K. Batra, Owais R. Hakiem, Lalit K. Singh |
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| Rok vydání: | 2019 |
| Předmět: |
Microbiology (medical)
Tuberculosis THP-1 Cells Regulator Stress tolerance Microbiology Mycobacterium tuberculosis 03 medical and health sciences Other systems of medicine Bacterial Proteins Stress Physiological Heat shock protein medicine Humans Cytokine Rv0384c 030304 developmental biology Infectivity 0303 health sciences Microbial Viability biology 030306 microbiology Macrophages Biofilm General Medicine Endopeptidase Clp biology.organism_classification medicine.disease QR1-502 Infectious Diseases Latency CLPB Bacteria RZ201-999 Caseinolytic protease |
| Zdroj: | International Journal of Medical Microbiology, Vol 310, Iss 3, Pp 151402-(2020) |
| ISSN: | 1618-0607 |
| Popis: | The ability to tolerate multiple host derived stresses, resist eradication and persist within the infected individuals is central to the pathogenicity of Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB). Mycobacterial survival is contingent upon sensing environmental perturbations and initiating a fitting response to counter them. Therefore, understanding of molecular mechanisms underlying stress tolerance and sensing in Mtb is critical for devising strategies for TB control. Our study aims to delineate the role of ClpB, a heat shock protein of Hsp100 family, in the general stress response and persistence mechanisms of Mtb. We demonstrate that Mtb requires ClpB to survive under stressful conditions. Additionally, we show that ClpB is necessary for the bacteria to persist in latency-like conditions such as prolonged hypoxia and nutrient-starvation. The disruption of ClpB results in aberrant cellular morphology, impaired biofilm formation and reduced infectivity of Mtb ex vivo. Our study also reports an alternative role of ClpB as a chaperokine which elicits inflammatory response in host. We conclude that ClpB is essential for Mtb to survive within macrophages, and plays a crucial part in the maintenance of dormant Mtb bacilli in latent state. The absence of ClpB in human genome makes it an attractive choice as drug target for TB. |
| Databáze: | OpenAIRE |
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