Mutations in the Plasmodium falciparum chloroquine resistance transporter, PfCRT, are the major determinant of chloroquine resistance in this lethal human malaria parasite. Here, we describe P. falciparum lines subjected to selection by amantadine or blasticidin that carry PfCRT mutations (C101F or L272F), causing the development of enlarged food vacuoles. These parasites also have increased sensitivity to chloroquine and some other quinoline antimalarials, but exhibit no or minimal change in sensitivity to artemisinins, when compared with parental strains. A transgenic parasite line expressing the L272F variant of PfCRT confirmed this increased chloroquine sensitivity and enlarged food vacuole phenotype. Furthermore, the introduction of the C101F or L272F mutation into a chloroquine-resistant variant of PfCRT reduced the ability of this protein to transport chloroquine by approximately 93 and 82%, respectively, when expressed in Xenopus oocytes. These data provide, at least in part, a mechanistic explanation for the increased sensitivity of the mutant parasite lines to chloroquine. Taken together, these findings provide new insights into PfCRT function and PfCRT-mediated drug resistance, as well as the food vacuole, which is an important target of many antimalarial drugs.

The identification of inhibitors effective against mutated PfATP6 suggests ways in which artemisinin resistance may be overcome.

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More than 60% of the 1,700 infectious diseases that affect human come from animals and zoonotic pandemics, after starting from sporadic phenomena limited to rural areas, have become a global emergency. The repeated and frequent zoonotic outbreaks such as the most recent COVID-19 pandemic can be attributed also to human activities. In particular, the creation of enormous intensive domestic animal farms, the indiscriminate use of antibiotics, the destruction of forests, the consumption of the meat of wild animals and the illegal animal trade are all factors causing the insurgence and the transmission of zoonotic diseases from animals to humans. The purpose of this study was to explore the knowledge of the One Health concept including the zoonotic risk potentially derived from illegally traded pet animals and wildlife among adolescents in 6 different countries (Italy, Austria, Slovenia, Germany, Mauritius, and Japan). A representative sample of 656 students was recruited and all participants took an anonymous questionnaire. Data were analyzed by ANOVAs to estimate the prevalence of correct health prevention behaviors and to identify the influential factors for these behaviors. After two theoretical-practical lectures, the same anonymous questionnaire was administered for the second time in order to assess the efficacy of the program. The proportion of students who did not know that many diseases affecting humans come from animals is 28.96% while 32.16% of them did not know what a zoonosis is. The circularity of the One Health concept related to the transmission of diseases from animals to humans and vice-versa is not understood from a large prevalence of the adolescents with 31.40 and 59.91% of wrong responses, respectively. Furthermore, rabies is not considered as a dangerous disease by 23.02% of the adolescents. After two theoretical-practical classroom sessions, the correct answers improved to 21.92% according to the different question. More than a third of the student cohort investigated showed a profound ignorance of the zoonotic risks and a poor understanding of the One Health concept. The authors believe that the teaching of health prevention with a One Health approach and a practical training should be included in every school curriculum.