Characterization of Metabolically Quiescent Parasites in Murine Lesions Using Heavy Water Labeling

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Microbial pathogens can adapt to changing conditions in their hosts by switching between different growth and physiological states. However, current methods for measuring microbial physiology in vivo are limited, hampering detailed dissection of host-pathogen interactions. Here we have used heavy water labeling to measure the growth rate and physiological state of Leishmania parasites in murine lesions. Based on the rate of in situ labeling of parasite DNA, RNA, protein, and lipids, we show that the growth rate of intracellular parasite stages is very slow, and that these stages enter a semi-quiescent state characterized by very low rates of RNA, protein, and membrane turnover. These changes in parasite growth and physiology are more pronounced than in in vitro differentiated parasites, suggesting that they are induced in part by the lesion environment. Despite their slow growth, the parasite burden in these lesions progressively increases as a result of low rates of parasite death and host cell turnover. We propose that these changes in Leishmania growth and physiology contribute to the development of a relatively benign tissue environment that is permissive for long term parasite expansion. This approach is suitable for studying the dynamics of other host-pathogen systems.

Vyšlo v časopise: Characterization of Metabolically Quiescent Parasites in Murine Lesions Using Heavy Water Labeling. PLoS Pathog 11(2): e32767. doi:10.1371/journal.ppat.1004683
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004683

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