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

摘要: Information on the growth rate and metabolism of microbial pathogens that cause long-term chronic infections is limited, reflecting absence suitable tools for measuring these parameters in vivo. Here, we have measured replication physiological state Leishmania mexicana parasites murine inflammatory lesions using 2H2O labeling. Infected BALB/c mice were labeled with up to 4 months, turnover parasite DNA, RNA, protein membrane lipids estimated from deuterium enrichment constituent pentose sugars, amino acids, fatty respectively. We show stages tissues very slow (doubling time ~12 days), but remarkably constant throughout lesion development. Lesion also exhibit markedly lower rates RNA synthesis, lipid synthesis than isolated ex vivo infected macrophages or cultured vitro, suggesting formation induces enter a semi-quiescent state. Significantly, determined accounts overall increase burden indicating death host cells minimal. propose response an important adaptive strategy minimizes macrophage activation, providing permissive environment supports progressive expansion burden. This labeling approach can be used measure dynamics other host-microbe interactions situ.