Viral symbiosis in Pseudomonas aeruginosa

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Just as virus particles are more numerous than the microbes they infect, it comes as no surprise to find that the majority of microbes themselves harbor viral sequences in their chromosome. Many of these viral sequences are complete, latent viral chromosomes which are also known as proviruses (in bacteria as prophages), and may be activated to cause death to its host cell in an abrupt frenzy of viral particle production.  Prophages are known to confer benefits on their hosts cells and can encode antibiotic resistance genes or promote lysogenic conversion. However, proviruses are often overlooked in considering the epidemiological impacts of microbes, even as the exogenous application of lytic phages on antibiotic-resistant infections is being increasingly recognized as an effective way to ecologically regulate the bacterial load.

Viruses are increasingly found  to be far from purely predatory. They often exhibit multi-dimensional relationships with the microbes they infect. In highly structured archaeal populations, complex viral infection dynamics arise from a mix of viral types (purely lytic viruses exist alongside chronic viruses which non-lethally extrude virion particles at a low rate) and immunity profiles of host cells. These infection dynamics have an enormous consequence on the host cells, where the chronic virus mediates death of uninfected cells. Infection with a chronic virus thus is an advantage to the hosts in this system, but may also provide evolutionary pressure on the transmission of the virus.

P. aeruginosa as a model system for viral symbiosis

P. aeruginosa is an opportunistic human pathogen, and can also be found in many human-associated environmental contexts. It follows well-defined adaptative and evolutionary trajectories following infection in the human lung of cystic fibrosis (CF) patients, and many strains have been cultivated for genetic tractability and lab use. P. aeruginosa can also be infected by a diversity of viruses, some of which are known to modulate virulence. P. aeruginosa strains also carry a Type 1 CRISPR-Cas system. This combination of factors make this organism ideal for further interrogating natural virus-host dynamics and setting these in a clinically relevant context.

P. aeruginosa CRISPR-Cas immunity

An open area of investigation in our lab is how CRISPR-mediated viral immunity shapes host-virus population structure. We’ve investigated CRISPR diversity within and between P. aeruginosa strains infecting CF patients and described immune structures in the lung, which allow inquiry into the evolutionary pressures that are applied by infecting viruses. In collaboration with others, our lab has also developed metrics which more accurately describe the structure of CRISPR immunity in microbial populations, and we are interested in applying these metrics in a predictive capacity to natural and clinical systems beyond P. aeruginosa. 

Genomics, and more

We are currently investigating evolutionary trajectories of P. aeruginosa and their viruses through metagenomics, experimental evolution, bioinformatic methods and high-throughput sequencing of CF clinical isolates. Potential students who are interested in these projects should contact Rachel.