Prospecting for zoonotic pathogens using targeted DNA enrichment

There are over 60 zoonoses linked to small mammals, including some of the most devastating pathogens in human history. Meanwhile, millions of museum-archived tissues are available to understand natural history of these pathogens. Our goal is to maximize the value of museum collections for pathogen-based research using targeted sequence capture. To this end, we have generated a probe panel that includes 39,916, 80bp RNA probes targeting 32 pathogen groups, including bacteria, helminths, fungi, and protozoans. Lab generated, mock control samples show that we are capable of enriching targeted loci from pathogen DNA 2,882 to 6,746-fold. Further, we were able to identify bacterial species in museum-archived samples, including Bartonella, a known human zoonosis. These results show that probe-based enrichment of pathogens is a highly customizable and efficient method for identifying pathogens from museum-archived tissues.