An -Methyltransferase Is Required for Infection of Tick Cells by

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Since its discovery in 1994, Human Granulocytic Anaplasmosis (HGA) has become the second most commonly diagnosed tick-borne disease in the US, and it is gaining importance in several countries in Europe. HGA is caused by Anaplasma phagocytophilum, a bacterium transmitted by black-legged ticks and their relatives. Whereas several of the molecules and processes leading to infection of human cells have been identified, little is known about their counterparts in the tick. We analyzed the effects of a mutation in a gene encoding an o-methyltransferase that is involved in methylation of an outer membrane protein. The mutation of the OMT appears to be important for the ability of A. phagocytophilum to adhere to, invade, and replicate in tick cells. Several tests including binding assays, microscopic analysis of the infection cycle within tick cells, gene expression assays, and biochemical assays using recombinant OMT strongly suggested that the mutation of the o-methyltransferase gene arrested the growth and development of this bacterium within tick cells. Proteomic analyses identified several possible OMT substrates, and in vitro methylation assays using recombinant o-methyltransferase identified an outer membrane protein, Msp4, as a specifically methyl-modified target. Our results indicated that methylation was important for infection of tick cells by A. phagocytophilum, and suggested possible strategies to block transmission of this emerging pathogen. The solved crystal structure of the o-methyltransferase will further stimulate the search for small molecule inhibitors that could break the tick transmission cycle of A. phagocytophilum in nature.

Vyšlo v časopise: An -Methyltransferase Is Required for Infection of Tick Cells by. PLoS Pathog 11(11): e32767. doi:10.1371/journal.ppat.1005248
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005248

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