Phenotypic diversity and selection maintain Leishmania amazonensis infectivity in BALB/c mouse model

Abstract

International audienceLeishmania are protozoan parasites that show remarkable diversity, as revealed by the various clinical forms of leishmaniasis,which can range from mild skin lesions to severe metastatic cutaneous/mucosal lesions. The exact nature andextent of Leishmania phenotypic diversity in establishing infection is not fully understood. In order to try to understandsome aspects of this diversity, we subcutaneously infected BALB/c mice with first and second generation subclones of aL. amazonensis strain isolated from a patient (BA125) and examined in vivo lesion growth rate and antimony susceptibility.In vivo fast-, medium- and slow-growing subclones were obtained; moreover, fast-growing subclones could generateslow-growing subclones and inversely, revealing the continuous generation of diversity after passage into mice. Noantimony-resistant subclone appeared, probably a rare occurrence. By tagging subclone cells with a L. amazonensisgenomic cosmid library, we found that only a very small number of founding cells could produce lesions. Leishmaniaclones transfected with in vivo selected individual cosmids were also diverse in terms of lesion growth rate, revealing thecosmid-independent intrinsic characteristics of each clone. Our results suggest that only a few of the infecting parasitesare able to grow and produce lesions; later, within the cell mixture of each lesion, there coexist several parasite populationswith different potentialities to grow lesions during the next infection round. This may reflect a sort of programmedheterogeneity of individual parasites, favoring the survival of some individuals in various environmental conditions