The Stavrinides Laboratory uses the multi-host and cross-kingdom pathogen, Pantoea, to explore and understand the underlying genetic basis of bacterial-host interactions, pathogen host range, and the evolution of host-specific adaptation.  We are also interested in the discovery and development of both natural and synthetic antibiotics for treatment of the ESKAPE pathogens, and the discovery of novel antifungals for use in agriculture.

Antibacterial and Antifungal Discovery
The increasing prevalence of antibiotic resistance among the "ESKAPE" bacterial pathogens (Enterococcus, Staphylococcus, Klebsiella, Pseudomonas, and Enterobacterposes a serious threat to human health.  We have begun to explore the natural products of Pantoea as potential therapeutics.  Members of Pantoea are very common environmental microbes, which produce a diversity of antimicrobials.  To date, we have identified many candidate antimicrobials, including four new Pantoea Natural Products that have antimicrobial activity against a diversity of human pathogens.  We have also established a collaboration with a chemist who has synthesized several novel synthetic compounds that have antimicrobial activity against many clinically relevant pathogens.  We are now working on identifying the spectrum of activity, biological target, mechanism of action, and potential cytotoxicity of these compounds.

(Left) Minimum inhibitory concentration of several synthetic compounds against Staphylococcus aureus
Klebsiella sp., Salmonella, enterica, and Streptococcus sp. (Right) Antibiotic activity of synthetic compounds 
against S. aureus.  

We are also currently pursuing the development of several new fungicides and fungal control agents to manage Ascochyta Blight. Members of Ascochyta cause blights and spots of pulses (lentil, chickpea, pea) and cereals (barley, wheat, maize, sorghum), resulting in significant crop losses annually. One species, Ascochyta rabiei, is a highly aggressive species that infects chickpea, and is presently a serious threat to the estimated 100,000 acres of chickpeas planted in Saskatchewan.  Integrated pest management strategies that incorporate strobilurin fungicides have been effective in reducing crop losses; however, recent surveys in Saskatchewan have revealed the evolution of strobilurin resistance, as well as resistance to other non-strobilurin antifungals.   

Genetic screening to identify mutants that are no longer
able to produce 
antifungals.  The well in the center shows
Ascochyta growing over a bacterial mutant.

Pantoea and host-association
Pantoea is found on plant surfaces in the environment and is known primarily for causing plant disease, yet it is closely related to the human pathogenic E. coli and Salmonella and is fully capable of infecting humans. Serious infections involving Pantoea have become increasingly more common in the nosocomial setting, some of which have resulted in human fatalities.  We use a combination of genetic, genomic, evolutionary, and bioinformatic approaches to address questions relating to host-specific virulence.  Our genetics approach involves genetic screening of Pantoea using the nematode, fruit fly, and several plants as hosts, with comparative virulence assays being used to identify host-specific disease determinants. 

(Left) Colonization of the nematode digestive tract by fluorescently-labeled bacteria.  (Right)  Close-up of nematode esophagus and crop colonized by fluorescently-labeled bacteria.  

As a complement to these genetic studies, we are conducting comparative genomic analyses of Pantoea isolates with different host affinities and pathogenic potential to delineate the specific evolutionary genomic changes that mediate the association between pathogen and host, and to gain a better understanding of host-specific adaptation. By comparing closely related clinical and environmental isolates, it is possible to reconstruct the stepwise evolutionary events that have allowed specific isolates to acclimate to one or many specific hosts. We are also currently exploring whether the nosocomial populations are distinct from the environmental populations.

Understanding the host range and virulence potential of bacterial pathogens is central to our ability to predict and control emerging and reemerging infectious diseases.  Knowledge of their specific host affinities and disease strategies is vital to assessing their evolutionary momentum and potential for emergence. My research has significant implications for understanding the evolutionary processes that govern host-specific virulence and pathogenicity, and the emergence of new infectious agents.