PPE51 mediates uptake of trehalose across the mycomembrane of Mycobacterium tuberculosis
The disaccharide trehalose is essential for viability of Mycobacterium tuberculosis , which synthesizes trehalose de novo but can also utilize exogenous trehalose. The mycobacterial cell wall encompasses two permeability barriers, the cytoplasmic membrane and the outer mycolic acid-containing mycome...
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Veröffentlicht in: | Scientific reports 2022-02, Vol.12 (1), p.2097-2097, Article 2097 |
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Sprache: | eng |
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Zusammenfassung: | The disaccharide trehalose is essential for viability of
Mycobacterium tuberculosis
, which synthesizes trehalose de novo but can also utilize exogenous trehalose. The mycobacterial cell wall encompasses two permeability barriers, the cytoplasmic membrane and the outer mycolic acid-containing mycomembrane. The ABC transporter LpqY–SugA–SugB–SugC has previously been demonstrated to mediate the specific uptake of trehalose across the cytoplasmic membrane. However, it is still unclear how the transport of trehalose molecules across the mycomembrane is mediated. In this study, we harnessed the antimycobacterial activity of the analogue 6-azido trehalose to select for spontaneous resistant
M. tuberculosis
mutants in a merodiploid strain harbouring two LpqY–SugA–SugB–SugC copies. Mutations mediating resistance to 6-azido trehalose mapped to the proline–proline–glutamate (PPE) family member PPE51 (Rv3136), which has recently been shown to be an integral mycomembrane protein involved in uptake of low-molecular weight compounds. A site-specific
ppe51
gene deletion mutant of
M. tuberculosis
was unable to grow on trehalose as the sole carbon source. Furthermore, bioorthogonal labelling of the
M. tuberculosis
Δ
ppe51
mutant incubated with 6-azido trehalose corroborated the impaired internalization. Taken together, the results indicate that the transport of trehalose and trehalose analogues across the mycomembrane of
M. tuberculosis
is exclusively mediated by PPE51. |
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ISSN: | 2045-2322 2045-2322 |
DOI: | 10.1038/s41598-022-06109-7 |