Tuesday, January 15, 2019

Viruses as Therapeutics: Advancements in Potential Phage Therapy




Recent research published by Princeton researchers has made large strides in understanding how viruses act in their inert phase and how biochemical coordination of dynamic phase can be closely related to the host cells that they infect. This work showed a viral strain VP882 (which is now one of many of its kind) that is capable of entering dynamic phase only when its bacterial host(s) have achieved quorum. It is upon this widespread biochemical quorum signaling that VP882 has been shown to enter the dynamic phase via microscopy of viral protein localization, killing its current host cells. This work practically creates a whole new field of study for virologists, as now the biochemical motivation of the viral inert to dynamic transition can be thoroughly evaluated. Further, it was shown that this switch can be flipped by using the supplementing these same quorum sensing molecules into the media and that this effect results in the death of bacterial hosts.  This technology suggests two major possibilities for this new sub-field of virology: the application of phage therapy in the prevention and treatment of bacterial biofilm-reliant infections (like complex urinary tract infections; cUTI, and acute bacterial skin and skin structure infections; ABSSSI) and the harnessing of the viral mechanism to help advance phage therapy mechanisms.



Many of the bacterial infections that must be combatted in patients rely on bacteria with mechanisms to avoid the immune system. Most of these systems for subverting the immune system rely on the ability of bacteria to produce small molecules that allow for them to communicate with other bacteria in the local region. This process, called quorum sensing, allows for bacterial cells (particularly in cUTI and ABSSSI) to collectively start producing a thick and relatively impermeable extracellular matrix at interfaces (solid-liquid, liquid-air, solid-air). These communities are then protected from immune mechanisms within the biofilm. While the cells on the outside of this film have reduced proliferative capacity, the inner population is rapidly dividing. In both of these types of infections, the dispersal of this now dangerous number of a single type of bacteria begins to infect non-resident tissues and can lead to serious infection. The idea that viruses can live inside of bacteria and kill them only when they undergo quorum sensing to form these dangerous biofilms is novel and immensely useful. In this case, the researchers were able to show that this virus is widely infective to bacteria. If this infectivity could be tuned to specific quorum sensing molecules, this population of viruses is a potentially effective prophylactic for populations at risk for these types of infections (burn victims, transplant patients, immunocompromised patients). This was a truly astounding discovery, and I for one will be watching closely to see how this work develops.




~Kyle Enriquez




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