On Monday, January 7, 2019, Dr. Patrick Secor from the University of Montana came to give a talk titled “Targeting bacteriophage to treat bacterial infections”. This is a novel approach towards treating bacterial infections. Normally, bacteriophages are thought of as a virus that harms bacteria and not humans. How would targeting bacteriophages help treat bacterial infections? Wouldn’t this be doing the opposite, because by killing bacteriophages you’re allowing for the bacteria to persist? Perhaps not as Dr. Secor’s work demonstrates a scenario where targeting bacteriophages therapeutically actually helps eliminate bacterial infection.
The Secor lab uses Pseudomonas aeruginosa as a model system. This bacterium is an opportunistic pathogen that takes advantage of immunocompromised hosts such as cystic fibrosis patients. Pf1-filamentous bacteriophage (Pf phage) are integrated into the chromosome of most P. aeruginosa strains, and Pf phage genes are some of the most highly upregulated when P. aeruginosa forms biofilms (1). The Secor lab found that Pf phage decreased bacterial invasiveness and were less inflammatory in mice. Furthermore, they found bacteria producing Pf phage were more resistant to phagocytosis by macrophages—phenotypes typically associated with chronic infection (2). These observations suggest that Pf phage play a role in infection pathogenesis. The lab has also found that the Pf phage is able to reduce bacterial clearance. Secor et al. hypothesize that Pf phage particles stimulate TLR3-TRIF signaling in macrophages. When TLR3 was disabled, TNF production by macrophages was restored. Additionally, their data showed that Pf phage co-localizes with TLR3. Overall, these results suggest that Pf phages are internalized by macrophages, where they trigger the TLR3-TRIF pathway, an antiviral response, which is able to reduce the bacterial clearance from sites of infection.
Overall, I think Dr. Secor’s work is fascinating and novel. This talk makes me curious as to whether or not eliminating bacteriophages, for example, by vaccination, could somehow help us solve the antimicrobial resistance (AMR) problem that we have been encountering. Of course, phages are viruses and, like bacteria, rapidly evolve. Therefore, maybe the answer to our AMR problem isn't in a vaccine. Nevertheless, Dr. Secor may have discovered an overarching mechanism that is used by bacteriophages to promote bacterial infections. If we can somehow understand the relationship between the two, we can then focus our efforts on targeting these specific mechanisms to treat bacterial infections without the use of antibiotics.
References:
Webb, Jeremy S., Mathew Lau, and Staffan Kjelleberg. "Bacteriophage and phenotypic variation in Pseudomonas aeruginosa biofilm development." Journal of bacteriology 186.23 (2004): 8066-8073.
Secor, Patrick R., et al. "Filamentous bacteriophage produced by Pseudomonas aeruginosa alters the inflammatory response and promotes noninvasive infection in vivo." Infection and immunity 85.1 (2017): e00648-16.