Transcript patterns elicited in response to hosts can reveal how fungi recognize suitable hosts and the mechanisms involved in pathogenicity. These patterns could be fashioned by recognition of host-specific topographical features or by chemical components displayed or released by the host. We investigated this in the specific locust pathogen Metarhizium anisopliae var. acridum. Only host (Schistocerca gregaria) cuticle stimulated the full developmental program of germination and differentiation of infection structures (appressoria). Cuticle from beetles (Leptinotarsa decimlineata) repressed germination while cuticle from hemipteran bugs (Magicicada septendecim) allowed germination but only very low levels of differentiation, indicating that the ability to cause disease can be blocked at different stages. Using organic solvents to extract insects we identified a polar fraction from locusts that allowed appressorial formation against a flat plastic (hydrophobic) surface. Microarrays comprising 1,730 expressed sequence tags were used to determine if this extract elicits different transcriptional programs than whole locust cuticle or nonhost extracts. Of 483 differentially regulated genes, 97% were upregulated. These included genes involved in metabolism, utilization of host cuticle components, cell survival and detoxification, and signal transduction. Surprisingly, given the complex nature of insect epicuticle components and the specific response of M. anisopliae var. acridum to locusts, very similar transcript profiles were observed on locust and beetle extracts. However, the beetle extract cluster was enriched in genes for detoxification and redox processes, while the locust extract upregulated more genes for cell division and accumulation of cell mass. In addition, several signal transduction genes previously implicated in pathogenicity in plant pathogens were only upregulated in response to locust extract, implying similarities in the regulatory circuitry of these pathogens with very different hosts.Many fungal insect pathogens, such as Metarhizium anisopliae, infect host cuticles via spores that adhere and germinate to form a series of infection structures during penetration. In the presence of nutrients and water, conidia of M. anisopliae form germ tubes. The germ tube continues undifferentiated hyphal growth on a soft surface or if nutrient quality and quantity is not conducive to differentiation. On a host cuticle, however, apical elongation terminates and the germ tube swells distally to form an appressorium, a major site of adhesion and for production of enzymes that help breach host cuticle and establish a nutritional relationship with the host (33, 38). The formation of appressoria by strains of M. anisopliae var. anisopliae with a broad host range can also be induced efficiently by a hard hydrophobic surface (i.e., polystyrene) in the presence of low levels of complex nitrogenous nutrients. However, pathogens with a narrow host range such as M. anisopliae var. acridum (specific for acridids) germinate...