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ArticleCurrent protein & peptide science2025

Comparative Proteomic Analysis of Cell Wall Proteins of Aminoglycosides Resistant and Sensitive

Devesh Sharma, Sakshi Gautam, Nalini Srivastava, Abdul Mabood Khan, Deepa Bisht

Abstract readComparative Study
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Article in Current protein & peptide science, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

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5 authors.

Devesh SharmaDepartment of Biochemistry, ICMR-National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Tajganj, Agra (UP)-282001, India.ORCID 0000-0003-0761-6732
Sakshi GautamDepartment of Biochemistry, ICMR-National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Tajganj, Agra (UP)-282001, India.ORCID 0000-0002-3252-8091
Nalini SrivastavaSchool of Studies in Biochemistry, Jiwaji University, Gwalior (MP)- 474011, India.
Abdul Mabood KhanDivision of Clinical Trails and Implementation Research, ICMR-National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Tajganj, Agra 282001, India.
Deepa BishtDepartment of Biochemistry, ICMR-National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Tajganj, Agra (UP)-282001, India.ORCID 0000-0001-5599-0775

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionThe rising prevalence of

aimThe study aimed to analyze the cell wall proteins overexpressed in aminoglycosides-resistant isolates of

methodsWe used two-dimensional electrophoresis and mass spectrometry to compare the cell wall proteomes of aminoglycosides-resistant and susceptible clinical isolates. The overexpressed protein spots were excised and identified using liquid chromatography-mass spectrometry (LC/MS). The identified proteins were subsequently analyzed for molecular docking, pupylation site identification, and STRING analysis.

resultsWe found a total of nine significantly upregulated proteins in aminoglycosides-resistant isolates. Three of these proteins were the same (isoform), resulting in the identification of seven unique proteins. Specifically, Rv3841 and Rv1308 belonged to intermediary metabolism and respiration; Rv2115c to the cell wall and cell processes; Rv2501c, Rv2247 and Rv0295c to lipid metabolism; and Rv2416c to virulence, detoxification/adaptation. Notably, variations in these proteins support cell wall integrity, aiding mycobacteria's establishment and proliferation. Molecular docking study revealed that both drugs bind strongly to the proteins' active site regions. Additionally, the GPS-PUP algorithm successfully identified possible pupylation sites within these proteins, except Rv0295c. Based on interactome analysis using the STRING 12.0 database, we have identified potential interactive partners suggesting their role in aminoglycosides resistance.

conclusionOverexpressed proteins not only act to counteract or regulate drug effects but also have a role in protein dynamics that allow for resistance. Some of these identified proteins may serve as innovative drug targets and biomarkers for the early detection of drug-specific resistance in M.tb. Further research is needed to elucidate the mechanisms by which these potential protein targets contribute to resistance in AK and KM M.tb isolates.

Indexed as

AminoglycosidesBacterial ProteinsCell WallDrug Resistance, BacterialMycobacterium tuberculosisProteomeProteomicsAntitubercular AgentsHumansMicrobial Sensitivity TestsMolecular Docking SimulationTuberculosisAminoglycosidesAntitubercular AgentsBacterial ProteinsProteomeAminoglycosidescell walldrug-resistancemass spectrometry.Mycobacterium tuberculosistwo-dimension electrophoresis gel

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