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Published on: February 23, 2021
Conservation of Putative Liquid-Liquid Phase Separating Proteins in Multiple Drug-Resistant Mycobacterium
Jasdeep Singh1,2, Prashant Pradhan3, Arti Kataria4
1Department of Chemistry and Biochemistry, University of Denver, Denver, Colorado 80210, United States.
Abstract:
We observed a high proportion of proteins in pathogenic Mycobacterium species that can potentially undergo liquid-liquid phase separation (LLPS) mediated biomolecular condensate formation, compared to nonpathogenic species. These proteins mainly include the PE-PPE and PE-PGRS families of proteins that have nucleic acid and protein-protein binding functions, typical of LLPS proteins. We also mapped identified LLPS proteins in M. tuberculosis (M.tb) drug-resistant databases PubMLST and TBProfiler, based upon the WHO 2023 catalogue of resistance-associated mutations. High sequence conservation of LLPS-associated proteins in various multiple drug-resistant M.tb isolates points to their potentially important role in virulence and host-pathogen interactions during pathogenic evolution. This analysis provides a perspective on the role of protein phase separation in the evaluation of M.tb pathogenesis and offers avenues for future research aimed at developing innovative strategies to combat M.tb infection.
Insights
Pathogenic bacteria like Mycobacterium species show more proteins capable of liquid-liquid phase separation (LLPS) than nonpathogenic ones. These proteins may be key to understanding tuberculosis virulence and developing new treatments.
Area of Science:
- Microbiology
- Molecular Biology
- Biochemistry
Background:
- Liquid-liquid phase separation (LLPS) drives biomolecular condensate formation, crucial for cellular organization.
- Pathogenic bacteria possess unique protein families, such as PE-PPE and PE-PGRS in Mycobacterium species, with potential roles in virulence.
Purpose of the Study:
- To investigate the prevalence of LLPS-associated proteins in pathogenic versus nonpathogenic Mycobacterium species.
- To explore the role of these LLPS proteins in Mycobacterium tuberculosis (M.tb) pathogenesis and drug resistance.
Main Methods:
- Comparative analysis of protein families involved in LLPS across different Mycobacterium species.
- Mapping of identified LLPS proteins in M.tb drug-resistant databases against WHO resistance-associated mutation catalogues.
Main Results:
- Pathogenic Mycobacterium species exhibit a higher proportion of proteins with LLPS potential, notably PE-PPE and PE-PGRS families.
- LLPS proteins show high sequence conservation in multidrug-resistant M.tb isolates, suggesting a role in virulence and host interactions.
Conclusions:
- LLPS proteins, particularly PE-PPE and PE-PGRS, are implicated in M.tb pathogenesis and virulence.
- Understanding protein phase separation offers novel strategies for combating M.tb infection and drug resistance.
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