Identification of host-specific virulence determinants in the opportunistic enteric pathogen, Pantoea

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Pantoea is a bacterial group that is closely related to human pathogenic, Enterobacter and E. coli, yet many isolates are currently registered in Canada as biological control agents for managing plant disease on crop plants. This is particularly concerning given that many Pantoea isolates have already been shown to cause plant disease themselves, as well as human disease. Pantoea has been noted to cause pulmonary infections, septicemia, and septic arthritis in both healthy and immunocompromised adults. The objective of this research program is to advance our understanding of the pathogenic ability of Pantoea, and more broadly, how pathogens adapt to exploit different hosts, including humans. This proposal rests on the hypothesis that there are specific disease determinants that enable Pantoea to cause disease in multiple hosts.***     The first objective is to identify candidate disease factors by comparing the genes of virulent and non-virulent isolates of Pantoea ananatis to identify those determinants that are present only in virulent isolates. To evaluate whether any of these genes are induced at human body temperature (37C), we will examine the expression of genes at 30C versus 37C using transcriptomic methods. The second objective is to evaluate whether genetic factors necessary for colonization of one host are needed for another host. This will be achieved using three mutant sets of P. ananatis, which were shown to be impaired in the ability to associate with either the fruit fly, nematode, or amoeba. Growth of the nematode and amoeba mutant sets will be evaluated in the model fruit fly to identify those genes that are specific to one host, or are needed for multiple hosts. The third objective will identify the genetic basis of hemolysin activity (lysis of red blood cells) exhibited by many Pantoea isolates at 37C. We will generate and screen mutant libraries for loss of hemolytic ability, thereby identifying the genes that are responsible for this capability. The fourth objective will evaluate the role of natural antibiotics produced by Pantoea during host association. Because hosts are often colonized by a variety of commensal bacteria, pathogens may enhance their ability to establish an infection by eliminating competing bacteria. Using fruit flies that are already infected with the pathogen Staphylococcus aureus, we will compare the colonization efficiency of an antibiotic-producing isolate to an antibiotic mutant to determine whether these natural products may be virulence factors that enhance host colonization.***     This research will identify virulence factors that contribute to the ability of Pantoea to cause disease in humans, and will allow us to assess the capacity for biological control strains to become pathogens. This research not only has broad implications for the regulation of biological control agents, but will also enhance our understanding of how bacteria evolve to become pathogenic.**