UC Santa Barbara

Bacterial infections impose some of the largest burdens on human health. Sepsis, typically induced by bacterial infections, accounts for more than 50% of hospital deaths in the United States. With an increase in bacteria resistant to antibiotics, developing tools that can detect bacteria and treat both bacterial contamination and infections is of paramount importance. Bacteriophage (phage) are bacterial viruses that are non-toxic to humans. They have evolved various mechanisms to target and damage host bacterial cells. Phages are easy to engineer and could be used as an additional instrument in the antimicrobial tool box to detect and treat bacterial infections. Through bioengineering phage we exploit their cell targeting capabilities and use them as a tunable scaffold for bacterial detection and therapeutic applications. The highly modular nature of phage allows for the detection of specific bacterial species ex vivo as well as in vivo. For rapid, inexpensive, and selective detection of bacterial pathogens in complex samples we use aggregation of gold nanoparticles induced by the enriched thiols of the phage that undergo a colorimetric change in the presence of target bacteria.

For therapeutics we have conjugated gold nanorods to the virions that then ablate target bacteria cells after irradiating the gold nanorods with near-infrared light. For in vivo applications virions loaded with MR contrast agent manganese have been shown to selectively detect target bacterial strains in a murine model. This diagnostic strategy integrates the highly specific targeting properties of bacteriophage with the MR contrast agents to create a modular platform for detecting target bacterial cells.