Lotmaria passim as an experimental model of trypanosomatid adaptation to the insect gut

<title>Abstract</title> <p> <italic>Lotmaria passim</italic> is a monoxenous trypanosomatid that persistently colonizes the hindgut of the western honey bee, <italic>Apis mellifera</italic> . Recent chromosome-level genome resources, reverse genetics, conditional protein depletion, omics approaches and experimental infection have shifted research on this parasite from detection surveys towards mechanistic analysis. Here, we synthesize evidence that genome plasticity, flagellar remodeling, Bardet–Biedl syndrome protein complex (BBSome)-dependent membrane organization, ergosterol biosynthesis and extracellular secretion collectively support parasite growth and hindgut colonization. Functional studies reveal that phenotypes observed in culture do not necessarily predict host fitness: loss of duplicated flagellar calcium-binding proteins impairs morphology and motility without substantially reducing infection, whereas disruption of BBS2, sterol C5-desaturase or the secreted aspartyl protease LpAsp compromises honey bee colonization. These findings identify membrane homeostasis, protein trafficking and extracellular functions, rather than motility alone, as important determinants of infection. We further propose <italic>L. passim</italic> as a comparative model for dissecting conserved insect-stage mechanisms shared with other monoxenous trypanosomatids and the insect stages of <italic>Leishmania</italic> and <italic>Trypanosoma cruzi</italic> . Resolving the signals and molecular machinery controlling haptomonad differentiation, attachment and extracellular community formation will clarify how trypanosomatids adapt to persistent extracellular growth in insect digestive tracts. </p>