Conservation of Putative Liquid-Liquid Phase Separating Proteins in Multiple Drug-Resistant Mycobacterium tuberculosis: Role in Host-Pathogen Interactions?

被引:0
|
作者
Singh, Jasdeep [1 ,7 ]
Pradhan, Prashant [2 ]
Kataria, Arti [3 ]
Sinha, Sanjeev [4 ]
Ehtesham, Nasreen Z. [5 ]
Monk, Peter N. [6 ]
Hasnain, Seyed E. [5 ,7 ]
机构
[1] Univ Denver, Dept Chem & Biochem, Denver, CO 80210 USA
[2] Univ Texas Southwestern Med Ctr, Cecil H & Ida Green Ctr Reprod Biol Sci, Hamon Ctr Regenerat Sci & Med,Dept Mol Biol,Div Ba, Dept Obstet & Gynecol,Lab Nucl Org,Dept Obstet & G, Dallas, TX 75390 USA
[3] Natl Inst Allergy & Infect Dis NIAID, Natl Inst Hlth NIH, Lab Bacteriol, Rocky Mt Labs, Hamilton, MT 59840 USA
[4] All India Inst Med Sci, Dept Med, Ansari Nagar, New Delhi 110029, India
[5] Sharda Univ, Sch Basic Sci & Res, Dept Life Sci, Greater Noida 201310, Uttar Pradesh, India
[6] Univ Sheffield, Dept Infect Immun & Cardiovasc Dis, Sheffield S10 2TN, England
[7] Indian Inst Technol Delhi, Dept Biochem Engn & Biotechnol, New Delhi 110016, India
来源
ACS INFECTIOUS DISEASES | 2025年
关键词
M; tuberculosis; Biomolecular condensates; Liquid-liquid phase separation; Host-pathogeninteractions; Functional genomics; MEMBRANE CHANNEL PROTEIN; PE/PPE MULTIGENE FAMILY;
D O I
10.1021/acsinfecdis.4c00722
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
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.
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页数:8
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