1887

Abstract

, the causative agent of plague, can be transmitted by fleas by two different mechanisms: by early-phase transmission (EPT), which occurs shortly after flea infection, or by blocked fleas following long-term infection. Efficient flea-borne transmission is predicated upon the ability of to be maintained within the flea. Signature-tagged mutagenesis (STM) was used to identify genes required for maintenance in a genuine plague vector, . The STM screen identified seven mutants that displayed markedly reduced fitness in fleas after 4 days, the time during which EPT occurs. Two of the mutants contained insertions in genes encoding glucose 1-phosphate uridylyltransferase () and UDP-4-amino-4-deoxy--arabinose-oxoglutarate aminotransferase (), which are involved in the modification of lipid A with 4-amino-4-deoxy--arabinose (Ara4N) and resistance to cationic antimicrobial peptides (CAMPs). These mutants were more susceptible to the CAMPs cecropin A and polymyxin B, and produced lipid A lacking Ara4N modifications. Surprisingly, an in-frame deletion of retained modest levels of CAMP resistance and Ara4N modification, indicating the presence of compensatory factors. It was determined that WecE, an aminotransferase involved in biosynthesis of enterobacterial common antigen, plays a novel role in Ara4N modification by partially offsetting the loss of These results indicated that mechanisms of Ara4N modification of lipid A are more complex than previously thought, and these modifications, as well as several factors yet to be elucidated, play an important role in early survival and transmission of in the flea vector.

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2015-03-01
2021-08-05
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