Teleological cooption of Mycobacterium tuberculosis PE/PPE proteins as porins: Role in molecular immigration and emigration
Permeation through bacterial cells for exchange or uptake of biomolecules and ions invariably depend upon the existence of pore-forming proteins (porins) in their outer membrane. Mycobacterium tuberculosis (M. tb) harbours one of the most rigid cell envelopes across bacterial genera and is devoid of...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-04-01
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| Series: | International Journal of Medical Microbiology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1438422121000242 |
| _version_ | 1818431347330383872 |
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| author | Aquib Ehtram Mohd Shariq Sabeeha Ali Neha Quadir Javaid A. Sheikh Faraz Ahmad Tarina Sharma Nasreen Z. Ehtesham Seyed E. Hasnain |
| author_facet | Aquib Ehtram Mohd Shariq Sabeeha Ali Neha Quadir Javaid A. Sheikh Faraz Ahmad Tarina Sharma Nasreen Z. Ehtesham Seyed E. Hasnain |
| author_sort | Aquib Ehtram |
| collection | DOAJ |
| description | Permeation through bacterial cells for exchange or uptake of biomolecules and ions invariably depend upon the existence of pore-forming proteins (porins) in their outer membrane. Mycobacterium tuberculosis (M. tb) harbours one of the most rigid cell envelopes across bacterial genera and is devoid of the classical porins for solute transport across the cell membrane. Though canonical porins are incompatible with the evolution of permeability barrier, porin like activity has been reported from membrane preparations of pathogenic mycobacteria. This suggests a sophisticated transport mechanism that has been elusive until now, along with the protein family responsible for it. Recent evidence suggests that these slow-growing mycobacteria have co-opted some of PE/PPE family proteins as molecular transport channels, in place of porins, to facilitate uptake of nutrients required to thrive in the restrictive host environment. These reports advocate that PE/PPE proteins, due to their structural ability, have a potential role in importing small molecules to the cell's interior. This mechanism unveils how a successful pathogen overcomes its restrictive membrane's transport limitations for selective uptake of nutrients. If extrapolated to have a role in drug transport, these channels could help understand the emergence of drug resistance. Further, as these proteins are associated with the export of virulence factors, they can be exploited as novel drug targets. There remains, however, an interesting question that as the PE/PPE proteins can allow the 'import' of molecules from outside the cell, is the reverse transport also possible across the M. tb membrane. In this review, we have discussed recent evidence supporting PE/PPE's role as a specific transport channel for selective uptake of small molecule nutrients and, as possible molecular export machinery of M. tb. This newly discovered role as transmembrane channels demands further research on this enigmatic family of proteins to comprehend the pathomechanism of this very smart pathogen. |
| first_indexed | 2024-12-14T15:47:52Z |
| format | Article |
| id | doaj.art-7c7cbb70030b4918a1ba66e76b5e755b |
| institution | Directory Open Access Journal |
| issn | 1438-4221 |
| language | English |
| last_indexed | 2024-12-14T15:47:52Z |
| publishDate | 2021-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | International Journal of Medical Microbiology |
| spelling | doaj.art-7c7cbb70030b4918a1ba66e76b5e755b2022-12-21T22:55:28ZengElsevierInternational Journal of Medical Microbiology1438-42212021-04-013113151495Teleological cooption of Mycobacterium tuberculosis PE/PPE proteins as porins: Role in molecular immigration and emigrationAquib Ehtram0Mohd Shariq1Sabeeha Ali2Neha Quadir3Javaid A. Sheikh4Faraz Ahmad5Tarina Sharma6Nasreen Z. Ehtesham7Seyed E. Hasnain8Kusuma School of Biological Sciences, Indian Institute of Technology Delhi, New Delhi, IndiaICMR-National Institute of Pathology, Ansari Nagar West, New Delhi, IndiaKusuma School of Biological Sciences, Indian Institute of Technology Delhi, New Delhi, IndiaICMR-National Institute of Pathology, Ansari Nagar West, New Delhi, India; Jamia Hamdard- Institute of Molecular Medicine, Jamia Hamdard, Hamdard Nagar, New Delhi, IndiaDepartment of Biotechnology, School of Chemical and Life Sciences, Jamia Hamdard, Hamdard Nagar, New Delhi, 110062, IndiaICMR-National Institute of Pathology, Ansari Nagar West, New Delhi, IndiaKusuma School of Biological Sciences, Indian Institute of Technology Delhi, New Delhi, India; ICMR-National Institute of Pathology, Ansari Nagar West, New Delhi, IndiaICMR-National Institute of Pathology, Ansari Nagar West, New Delhi, India; Corresponding author.Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology Delhi, New Delhi, India; Dr Reddy's Institute of Life Sciences, University of Hyderabad Campus, Hyderabad, India; Corresponding author at: Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology Delhi, New Delhi, India.Permeation through bacterial cells for exchange or uptake of biomolecules and ions invariably depend upon the existence of pore-forming proteins (porins) in their outer membrane. Mycobacterium tuberculosis (M. tb) harbours one of the most rigid cell envelopes across bacterial genera and is devoid of the classical porins for solute transport across the cell membrane. Though canonical porins are incompatible with the evolution of permeability barrier, porin like activity has been reported from membrane preparations of pathogenic mycobacteria. This suggests a sophisticated transport mechanism that has been elusive until now, along with the protein family responsible for it. Recent evidence suggests that these slow-growing mycobacteria have co-opted some of PE/PPE family proteins as molecular transport channels, in place of porins, to facilitate uptake of nutrients required to thrive in the restrictive host environment. These reports advocate that PE/PPE proteins, due to their structural ability, have a potential role in importing small molecules to the cell's interior. This mechanism unveils how a successful pathogen overcomes its restrictive membrane's transport limitations for selective uptake of nutrients. If extrapolated to have a role in drug transport, these channels could help understand the emergence of drug resistance. Further, as these proteins are associated with the export of virulence factors, they can be exploited as novel drug targets. There remains, however, an interesting question that as the PE/PPE proteins can allow the 'import' of molecules from outside the cell, is the reverse transport also possible across the M. tb membrane. In this review, we have discussed recent evidence supporting PE/PPE's role as a specific transport channel for selective uptake of small molecule nutrients and, as possible molecular export machinery of M. tb. This newly discovered role as transmembrane channels demands further research on this enigmatic family of proteins to comprehend the pathomechanism of this very smart pathogen.http://www.sciencedirect.com/science/article/pii/S1438422121000242PE/PPEPorinCell envelopDrug resistanceMolecular transportNutrient uptake |
| spellingShingle | Aquib Ehtram Mohd Shariq Sabeeha Ali Neha Quadir Javaid A. Sheikh Faraz Ahmad Tarina Sharma Nasreen Z. Ehtesham Seyed E. Hasnain Teleological cooption of Mycobacterium tuberculosis PE/PPE proteins as porins: Role in molecular immigration and emigration International Journal of Medical Microbiology PE/PPE Porin Cell envelop Drug resistance Molecular transport Nutrient uptake |
| title | Teleological cooption of Mycobacterium tuberculosis PE/PPE proteins as porins: Role in molecular immigration and emigration |
| title_full | Teleological cooption of Mycobacterium tuberculosis PE/PPE proteins as porins: Role in molecular immigration and emigration |
| title_fullStr | Teleological cooption of Mycobacterium tuberculosis PE/PPE proteins as porins: Role in molecular immigration and emigration |
| title_full_unstemmed | Teleological cooption of Mycobacterium tuberculosis PE/PPE proteins as porins: Role in molecular immigration and emigration |
| title_short | Teleological cooption of Mycobacterium tuberculosis PE/PPE proteins as porins: Role in molecular immigration and emigration |
| title_sort | teleological cooption of mycobacterium tuberculosis pe ppe proteins as porins role in molecular immigration and emigration |
| topic | PE/PPE Porin Cell envelop Drug resistance Molecular transport Nutrient uptake |
| url | http://www.sciencedirect.com/science/article/pii/S1438422121000242 |
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