The role of ABC transporter DrrABC in the export of PDIM in Mycobacterium tuberculosis
The Mycobacterium tuberculosis virulence lipid phthiocerol dimycocerosate (PDIM) is exported by a complex mechanism that involves multiple proteins including the Resistance-Nodulation-Division (RND) transporter MmpL7 and the lipoprotein LppX. Here, we probe the role of the putative heterooligomeric...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-12-01
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| Series: | The Cell Surface |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2468233024000148 |
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| author | Nabiela Moolla Helen Weaver Rebeca Bailo Albel Singh Vassiliy N. Bavro Apoorva Bhatt |
| author_facet | Nabiela Moolla Helen Weaver Rebeca Bailo Albel Singh Vassiliy N. Bavro Apoorva Bhatt |
| author_sort | Nabiela Moolla |
| collection | DOAJ |
| description | The Mycobacterium tuberculosis virulence lipid phthiocerol dimycocerosate (PDIM) is exported by a complex mechanism that involves multiple proteins including the Resistance-Nodulation-Division (RND) transporter MmpL7 and the lipoprotein LppX. Here, we probe the role of the putative heterooligomeric ATP-Binding Cassette (ABC) transporter complex composed of DrrA, DrrB and DrrC in PDIM transport by constructing a set of individual null mutants of drrA, drrB and drrC in the vaccine strain Mycobacterium bovis BCG. Loss of all three, or individual drr genes, all resulted in a complete loss of PDIM export to the outer envelope of the mycobacterial cell. Furthermore, guided by a bioinformatic analysis we interrogated specific signature residues within the DrrABC to demonstrate that it is indeed an ABC transporter, and our modelling, together with the mutagenesis identify it as a member of the Type V family of ABC exporters. We identify several unique structural elements of the transporter, including a non-canonical C-terminally inserted domain (CTD) structure within DrrA, which may account for its functional properties. |
| format | Article |
| id | doaj-art-6dee0c938b9a4a4cbb2d52de9f4451c8 |
| institution | DOAJ |
| issn | 2468-2330 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | The Cell Surface |
| spelling | doaj-art-6dee0c938b9a4a4cbb2d52de9f4451c82025-08-20T02:50:20ZengElsevierThe Cell Surface2468-23302024-12-011210013210.1016/j.tcsw.2024.100132The role of ABC transporter DrrABC in the export of PDIM in Mycobacterium tuberculosisNabiela Moolla0Helen Weaver1Rebeca Bailo2Albel Singh3Vassiliy N. Bavro4Apoorva Bhatt5School of Biosciences and Institute of Microbiology and Infection, University of Birmingham, Edgbaston, Birmingham B15 2TT, United KingdomSchool of Biosciences and Institute of Microbiology and Infection, University of Birmingham, Edgbaston, Birmingham B15 2TT, United KingdomSchool of Biosciences and Institute of Microbiology and Infection, University of Birmingham, Edgbaston, Birmingham B15 2TT, United KingdomSchool of Biosciences and Institute of Microbiology and Infection, University of Birmingham, Edgbaston, Birmingham B15 2TT, United KingdomSchool of Life Sciences, University of Essex, Colchester CO4 3SQ, United Kingdom; Corresponding authors.School of Biosciences and Institute of Microbiology and Infection, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom; Corresponding authors.The Mycobacterium tuberculosis virulence lipid phthiocerol dimycocerosate (PDIM) is exported by a complex mechanism that involves multiple proteins including the Resistance-Nodulation-Division (RND) transporter MmpL7 and the lipoprotein LppX. Here, we probe the role of the putative heterooligomeric ATP-Binding Cassette (ABC) transporter complex composed of DrrA, DrrB and DrrC in PDIM transport by constructing a set of individual null mutants of drrA, drrB and drrC in the vaccine strain Mycobacterium bovis BCG. Loss of all three, or individual drr genes, all resulted in a complete loss of PDIM export to the outer envelope of the mycobacterial cell. Furthermore, guided by a bioinformatic analysis we interrogated specific signature residues within the DrrABC to demonstrate that it is indeed an ABC transporter, and our modelling, together with the mutagenesis identify it as a member of the Type V family of ABC exporters. We identify several unique structural elements of the transporter, including a non-canonical C-terminally inserted domain (CTD) structure within DrrA, which may account for its functional properties.http://www.sciencedirect.com/science/article/pii/S2468233024000148 |
| spellingShingle | Nabiela Moolla Helen Weaver Rebeca Bailo Albel Singh Vassiliy N. Bavro Apoorva Bhatt The role of ABC transporter DrrABC in the export of PDIM in Mycobacterium tuberculosis The Cell Surface |
| title | The role of ABC transporter DrrABC in the export of PDIM in Mycobacterium tuberculosis |
| title_full | The role of ABC transporter DrrABC in the export of PDIM in Mycobacterium tuberculosis |
| title_fullStr | The role of ABC transporter DrrABC in the export of PDIM in Mycobacterium tuberculosis |
| title_full_unstemmed | The role of ABC transporter DrrABC in the export of PDIM in Mycobacterium tuberculosis |
| title_short | The role of ABC transporter DrrABC in the export of PDIM in Mycobacterium tuberculosis |
| title_sort | role of abc transporter drrabc in the export of pdim in mycobacterium tuberculosis |
| url | http://www.sciencedirect.com/science/article/pii/S2468233024000148 |
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