Infections caused by multidrug-resistant (MDR) bacteria are a growing public health concern, which is driving exploration of novel antibacterial treatments such as phage therapy. The CPT remains at the forefront of developing phage therapy for human clinical applications since our significant role in the first well-documented application of phage therapy in modern medicine in 2016 (known as the “Tom Patterson Case“). With our accumulated expertise in this field and leveraging our largest standing collections of phages, we are addressing bottlenecks that limit the performance of natural phages relied upon in current practices.  Our phage therapy research is currently generously supported by the Thomas L. Patterson Graduate Fellowship (established by Drs. Tom Patterson and Steffanie Strathdee), as well as Love, Tito’s — the philanthropic heart of Tito’s Handmade Vodka, and the Cystic Fibrosis Foundation.

In developing phages for use as therapeutics, naturally-occurring phages with the desired host range or lytic capacity are often not easily found in the environment. Jason Gill and Carlos Gonzalez have led teams to engineer phages to render temperate phages strictly virulent and to produce expanded host range within a target species. This is done by a combination of natural selection processes and alteration or swapping of the phage tail fibers. A major component of successful engineering is understanding phage and host factors that control phage host range, which includes host recognition by phage tail fibers and also the presence of anti-phage defense systems. Phage engineering efforts are currently focused on phages infecting pathogenic Burkholderia that cause infection in cystic fibrosis patients.

Specific phage proteins are produced that target and breach each layer of the cell wall, thereby blocking phage exit from the cell. In Gram-negative host cells, phages use several classes of lysis protein to achieve this. Although there are unifying themes among phages with different lysis protein combinations, new themes have emerged from the study of lysis in both well-known and understudied phages. The Ramsey lab is currently working on projects that seek to understand how each lysis protein functions in several experimental systems, as well as the regulatory mechanisms that govern their activity, by employing both wet bench techniques and genomics. See Ramsey lab page for details.

As a temperate phage, upon infecting an E. coli cell, lambda can choose either the lytic (virulent) pathway producing ~100 new progeny particles and lysing the cell, or the lysogenic (dormant) pathway with its DNA integrated into the host chromosome and replicating along with the host. The Zeng Lab is interested in examining subcellular decision-making processes and cellular dynamics in various systems, primarily to determine how multiple environmental and genetic factors — some deterministic, some stochastic — impact developmental outcomes. Using high-resolution and super-resolution fluorescence microscopy combined with mathematical modelling, the Zeng Lab aims to formulate a quantitative picture of the phage lysis-lysogeny decision-making process. For details, see Zeng lab page.

The single‐stranded ribonucleic acid (ssRNA) phages are small viruses which infect their host via retractile pili. The research by the Zeng lab and the Zhang lab focus on the entry dynamics of genomic RNA from the phage capsid into the cell, as well as on virus replication and assembly inside the cell. The research also considers the impact of ssRNA phage infection on retractile pili. The aim of the research is to understand these fundamental processes and engineer these phages as a new type of antibacterial agent.

First phage product for Pierce’s disease in grapevines

Lead by Carlos Gonzalez and sponsored by A&P Inphatec, the CPT has developed the world’s first curative and preventive phage product against the pathogen Xylella fastidiosa, which causes the deadly Pierce’s disease in grapevines.

Phage-based prebiotics

The phage-based prebiotic PreForPro was initially developed in the CPT with the support of Deerland Enzymes (ADM), for promoting human gut health.

A droplet platform for phage isolation and characterization

Through collaboration with TAMU’s NanoBio Systems Lab (lead by Arum Han) and support by DARPA, a unified platform (“PRISM“) from single-droplet microenvironments was developed for isolating and characterizing phages that are difficult to culture via conventional methods.

phage-based protein production and delivery

Through genetic engineering, we intend to utilize phage to overproduce and deliver proteins or protein complexes in both clinical and industrial settings. We are currently seeking partnership with researchers and companies with high-value targets to deliver therapeutics in diverse settings.