The bacteriophage therapy is an effective antimicrobial approach with potentially important applications in medicine and biotechnology which can be seen as an additional string in the bow. Emerging drug resistant bacteria in aquaculture industry due to unrestricted use of antibiotics warrants more sustainable and environmental friendly strategies for controlling fish infections.
Background: Monitoring resistance phenotypes forPlasmodium falciparum, usingin vitrogrowth assays, and relating findings to parasite genotype has proved particularly challenging for the study of resistance to artemisinins.Methods: Plasmodium falciparumisolates cultured from 28 returning travellers diagnosed with malaria were assessed for sensitivity to artemisinin, artemether, dihydroartemisinin and artesunate and findings related to mutations inpfatp6andpfmdr1.Results: Resistance to artemetherin vitrowas significantly associated with apfatp6haplotype encoding two amino acid substitutions (pfatp6A623E and S769N; (mean IC50(95% CI) values of 8.2 (5.7 – 10.7) for A623/S769versus623E/769 N 13.5 (9.8 – 17.3) nM with a mean increase of 65%; p = 0.012). Increased copy number ofpfmdr1was not itself associated with increased IC50values for artemether, but when interactions between thepfatp6haplotype and increased copy number ofpfmdr1were examined together, a highly significant association was noted with IC50values for artemether (mean IC50(95% CI) values of 8.7 (5.9 – 11.6)versus16.3 (10.7 – 21.8) nM with a mean increase of 87%; p = 0.0068). Previously described SNPs inpfmdr1are also associated with differences in sensitivity to some artemisinins.Conclusions: These findings were further explored in molecular modelling experiments that suggest mutations inpfatp6are unlikely to affect differential binding of artemisinins at their proposed site, whereas there may be differences in such binding associated with mutations inpfmdr1. Implications for a hypothesis that artemisinin resistance may be exacerbated by interactions between PfATP6 and PfMDR1 and for epidemiological studies to monitor emerging resistance are discussed.