Abstract

Obligate intracellular pathogens depend on their host for growth yet must also evade detection by host defenses. Here we investigate host adaptation in two Microsporidia, the specialist Edhazardia aedis and the generalist Vavraia culicis, pathogens of disease vector mosquitoes. Genomic analysis and deep RNA-Seq across infection time courses reveal fundamental differences between these pathogens. E. aedis retains enhanced cell surface modification and signalling capacity, upregulating protein trafficking and secretion dynamically during infection. V. culicis is less dependent on its host for basic metabolites and retains a subset of spliceosomal components, with a transcriptome broadly focused on growth and replication. Transcriptional profiling of mosquito immune responses reveals that response to infection by E. aedis differs dramatically depending on the mode of infection, and that antimicrobial defensins may play a general role in mosquito defense against Microsporidia. This analysis illuminates fundamentally different evolutionary paths and host interplay of specialist and generalist pathogens.

Highlights

  • Obligate intracellular pathogens depend on their host for growth yet must evade detection by host defenses

  • We describe the genome sequence of E. aedis and V. culicis, and identify the key differences in these species that resulted from genome contraction under differing selective pressures

  • We identified 335 and 169 secreted proteins in the E. aedis and V. culicis genomes, respectively, that are expressed during infection but have no predicted domains; most of the proteins appear species-specific (Table 1, Methods)

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Summary

Introduction

Obligate intracellular pathogens depend on their host for growth yet must evade detection by host defenses. Transcriptional profiling of mosquito immune responses reveals that response to infection by E. aedis differs dramatically depending on the mode of infection, and that antimicrobial defensins may play a general role in mosquito defense against Microsporidia. This analysis illuminates fundamentally different evolutionary paths and host interplay of specialist and generalist pathogens. Obligate intracellular pathogens rely on a complex interplay with their hosts; they must acquire nutrients and other metabolites within the host cell, yet evade its defenses. The infective stage of Microsporidia in the spore includes a highly developed injection apparatus used to penetrate the host cell (Fig. 1a,b). We investigate genome reduction and host–pathogen interactions in two Microsporidia, one specializing on a single host and one infecting a wider range of species, that naturally

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