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Updated: May 15, 2026
Separation and Fractionation of Cell Wall and Cell Membrane Proteins from Mycobacterium tuberculosis for Downstream Protein Analysis
Published on: September 26, 2025
Bioinformatic identification of Mycobacterium tuberculosis proteins likely to target host cell mitochondria:
María Maximina Bertha Moreno-Altamirano1, Iris Selene Paredes-González, Clara Espitia
1Laboratorio de Inmunorregulación, Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Carpio y Plan de Ayala, Col, Sto, Tomás, México D,F, México. fsanchez_1@yahoo.co.uk.
Background:
M. tuberculosis infection either induces or inhibits host cell death, depending on the bacterial strain and the cell microenvironment. There is evidence suggesting a role for mitochondria in these processes.On the other hand, it has been shown that several bacterial proteins are able to target mitochondria, playing a critical role in bacterial pathogenesis and modulation of cell death. However, mycobacteria-derived proteins able to target host cell mitochondria are less studied.
Results:
A bioinformaic analysis based on available genomic sequences of the common laboratory virulent reference strain Mycobacterium tuberculosis H37Rv, the avirulent strain H37Ra, the clinical isolate CDC1551, and M. bovis BCG Pasteur strain 1173P2, as well as of suitable bioinformatic tools (MitoProt II, PSORT II, and SignalP) for the in silico search for proteins likely to be secreted by mycobacteria that could target host cell mitochondria, showed that at least 19 M. tuberculosis proteins could possibly target host cell mitochondria. We experimentally tested this bioinformatic prediction on four M. tuberculosis recombinant proteins chosen from this list of 19 proteins (p27, PE_PGRS1, PE_PGRS33, and MT_1866). Confocal microscopy analyses showed that p27, and PE_PGRS33 proteins colocalize with mitochondria.
Conclusions:
Based on the bioinformatic analysis of whole M. tuberculosis genome sequences, we propose that at least 19 out of 4,246 M. tuberculosis predicted proteins would be able to target host cell mitochondria and, in turn, control mitochondrial physiology. Interestingly, such a list of 19 proteins includes five members of a mycobacteria specific family of proteins (PE/PE_PGRS) thought to be virulence factors, and p27, a well known virulence factor. P27, and PE_PGRS33 proteins experimentally showed to target mitochondria in J774 cells. Our results suggest a link between mitochondrial targeting of M. tuberculosis proteins and virulence.
Insights
Mycobacterium tuberculosis proteins can target host cell mitochondria, influencing cell death and virulence. Researchers identified 19 potential mitochondrial-targeting proteins, with p27 and PE_PGRS33 experimentally confirmed to interact with mitochondria.
Area of Science:
- Microbiology
- Cell Biology
- Bioinformatics
Background:
- Tuberculosis pathogenesis involves host cell death modulation by Mycobacterium tuberculosis.
- Mitochondria play a role in these host cell death processes.
- Bacterial proteins targeting host mitochondria are critical for pathogenesis but less studied in mycobacteria.
Purpose of the Study:
- To identify Mycobacterium tuberculosis proteins that target host cell mitochondria.
- To investigate the role of these proteins in virulence and host cell death.
Main Methods:
- Bioinformatic analysis of M. tuberculosis genomic sequences using MitoProt II, PSORT II, and SignalP.
- In silico prediction of mitochondrial-targeting proteins.
- Experimental validation using recombinant proteins (p27, PE_PGRS1, PE_PGRS33, MT_1866) and confocal microscopy.
Main Results:
- At least 19 M. tuberculosis proteins were predicted to target host cell mitochondria.
- Experimental validation confirmed that p27 and PE_PGRS33 proteins colocalize with mitochondria in J774 cells.
- The identified proteins include virulence factors like p27 and PE/PE_PGRS family members.
Conclusions:
- A significant number of M. tuberculosis proteins are predicted to target host mitochondria.
- Mitochondrial targeting by M. tuberculosis proteins, such as p27 and PE_PGRS33, is linked to bacterial virulence.
- These findings suggest a novel mechanism of pathogenesis involving mitochondrial manipulation.
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