Profiles

Jonathan Allen, Ph.D.

Research Interests

Major Research Interests: We are interested in the molecular mechanisms by which the opportunistic pathogen Pseudomonas aeruginosa is able to cause severe and invasive infections.  

Pseudomonas aeruginosa is an important opportunistic human pathogen of increasing concern. It is capable of causing numerous different infections of a compromised host and isolates with resistance to multiple common antibiotic treatment therapies are an emerging problem. Novel approaches for dealing with P. aeruginosa infections will require a deeper understanding of the pathogenic mechanisms utilized by this organism. Our goal is to elucidate these specific virulence mechanisms to stimulate the development of novel therapeutic strategies against invasive P. aeruginosa infections.

We are currently investigating a unique role for Contact-Dependent growth Inhibition (CDI) systems in the virulence of P. aeruginosa. CDI systems are used in bacterial competition to hinder the growth of neighboring microbes. The exoprotein CdiA forms a long filamentous stalk that facilitates delivery of a C-terminal toxin (CT) domain. CdiA-CT domains vary among strains within a species, and many alleles encode enzymatic functions that target nucleic acids. This variation is thought to help drive diversity and adaptation within a species. We have observed that certain CdiA-CT domains assist in P. aeruginosa pathogenesis with direct effects on cell toxicity and bacterial survival in murine infection models. Our research uses bacterial genetics, biochemistry, cell biology and murine infection models to understand how a system evolved for use in bacterial competition serves a dual role in the pathogenesis of P. aeruginosa.

In addition, we use a variety of imaging and genomics-based tools to understand what happens to P. aeruginosa during the course of an invasive infection. We have determined that the initial population of infecting organisms experiences a large bottleneck, likely imposed by the spleen and liver. We have also determined that a small population of organisms in the liver escape to the gallbladder and replicate unimpeded to high levels. This massive replication promotes bacterial dissemination to the intestinal tract and excretion in the feces. This type of bacterial escape has substantial clinical implications concerning transmission and secondary infection. We will continue to investigate the role of bacterial dissemination to the biliary and intestinal tracts, and elucidate the host-microbe interactions at the spleen and liver. We anticipate this work will highlight key breakpoints during P. aeruignosa infection that can be targeted for specific therapies.

Selected Publications

Allen JP, Ozer EA, Minasov G, Shuvalova L, Kiryukhina O, Satchell K, Hauser AR. (2020). A Comparative Genomics Approach Identifies Contact-Dependent Growth Inhibition as a Virulence Determinant. PNAS. Accepted.

*Bachta KER, *Allen JP, Hauser AR. (2020). Systemic Infection Facilitates Transmission of Pseudomonas aeruginosa. Nature Communications. Accepted.  *Contributed Equally.

Allen JP, Hauser AR. (2018). Diversity of Pseudomonas aeruginosa contact-dependent growth inhibition systems. J. Bacteriol. 201. e00776-18

Allen,JP, Ozer EA, Hauser AR. (2014). Different paths to pathogenesis. Trends Microbiol. 4:168-169.

Ozer EA, Allen JP, Hauser AR. (2014). Characterization of the core and accessory genomes of Pseudomonas aeruginosa using bioinformatics tools Spine and AGEnt. BMC Genomics. 15:737 doi: 101186/1471-2164-15-737.

Chuang CH, Wang YH, Chang HJ, Chen HL, Huang YC, Lin TO, Ozer EA, Allen JP, Hauser AR, Chiu CH. (2013). Shanghai fever: a distinct Pseudomonas aeruginosa enteric disease. Gut. 63:736-743.

Hattemer A, Hauser A, Diaz M, Scheetz M, Shah N, Allen JP, Porhomayon J, El-Solh AA.  (2013). Bacterial and clinical characteristics of health care- and community-acquired bloodstream infections due to Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 57:3969-3975.