ORCID Profile
0000-0002-2205-8102
Current Organisations
University of Minho
,
Zhejiang University
,
Karolinska Institutet
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Publisher: Springer Science and Business Media LLC
Date: 18-05-2016
DOI: 10.1038/NCOMMS11553
Abstract: Antimalarial chemotherapy, globally reliant on artemisinin-based combination therapies (ACTs), is threatened by the spread of drug resistance in Plasmodium falciparum parasites. Here we use zinc-finger nucleases to genetically modify the multidrug resistance-1 transporter PfMDR1 at amino acids 86 and 184, and demonstrate that the widely prevalent N86Y mutation augments resistance to the ACT partner drug amodiaquine and the former first-line agent chloroquine. In contrast, N86Y increases parasite susceptibility to the partner drugs lumefantrine and mefloquine, and the active artemisinin metabolite dihydroartemisinin. The PfMDR1 N86 plus Y184F isoform moderately reduces piperaquine potency in strains expressing an Asian/African variant of the chloroquine resistance transporter PfCRT. Mutations in both digestive vacuole-resident transporters are thought to differentially regulate ACT drug interactions with host haem, a product of parasite-mediated haemoglobin degradation. Global mapping of these mutations illustrates where the different ACTs could be selectively deployed to optimize treatment based on regional differences in PfMDR1 haplotypes.
Publisher: Wiley
Date: 26-05-2017
Abstract: Interactions among microbes determine the prevalence of harmful algal blooms that threaten water quality. These interactions can be indirectly mediated by shared resources or consumers, or through interference by the production of allelochemicals. Allelopathic interactions and resource competition have been shown to occur among algae and associated microbes. However, little work has considered seasonal influences on ecosystem structure and function. Here, we report results of our investigations on seasonal changes in the interactions between benthic microbial assemblies and the bloom forming cyanobacterium Microcystis aeruginosa. We show that phosphorus (P) competition and allelopathy by the microbial assembly vary seasonally and inhibit growth of M. aeruginosa. The interactions per unit biomass of the microbial assembly are stronger under winter than summer conditions and inhibit the recruitment of the cyanobacteria, thereby preventing the reoccurrence of cyanobacterial blooms in the following summer. The seasonality of these interactions correlates with changes in composition, metabolic activity and functional ersity of the microbial assembly. Our findings highlight the importance of competitive and allelopathic interactions in regulating the occurrence of harmful algal blooms. Our results also imply that seasonal variation of competition and allelopathy of the microbial assembly might be beneficial to adjust aquatic ecosystem structure and function.
Publisher: Springer Science and Business Media LLC
Date: 14-08-2017
Publisher: Oxford University Press (OUP)
Date: 03-2009
DOI: 10.1086/596738
Location: United States of America
No related grants have been discovered for Maria Isabel Veiga.