期刊
MOLECULAR MICROBIOLOGY
卷 90, 期 2, 页码 428-442出版社
WILEY
DOI: 10.1111/mmi.12374
关键词
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资金
- European Commission (Kaladrug-R) [222895]
- Belgian Science Policy Office (TRIT) [P7/41]
- Flemish Fund for Scientific research [G.0B81.12, G.0552.10]
- Flemish Ministry of Sciences (ITMA SOFI-B GeMInI)
- Inbev-Baillet Latour Fund [620001]
- FWO credit Lumicor [1.5.147.09]
Antimonial (sodium stibogluconate, SSG) resistance and differentiation have been shown to be closely linked in Leishmania donovani, with SSG-resistant strains showing an increased capacity to generate infectious (metacyclic) forms. This is the first untargeted LC-MS metabolomics study which integrated both phenomena in one experimental design and provided insights into metabolic differences between three clinical L.donovani strains with a similar genetic background but different SSG-susceptibilities. We performed this analysis at different stages during promastigote growth and in the absence or presence of drug pressure. When comparing SSG-resistant and SSG-sensitive strains, a number of metabolic changes appeared to be constitutively present in all growth stages, pointing towards a clear link with SSG-resistance, whereas most metabolic changes were only detected in the stationary stage. These changes reflect the close intertwinement between SSG-resistance and an increased metacyclogenesis in resistant parasites. The metabolic changes suggest that SSG-resistant parasites have (i) an increased capacity for protection against oxidative stress; (ii) a higher fluidity of the plasma membrane; and (iii) a metabolic survival kit to better endure infection. These changes were even more pronounced in a resistant strain kept under Sb-III drug pressure.
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