CAMPOS-GOMEZ
LABORATORY

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Research Focus

The major research efforts of our laboratory are aimed at the identification, molecular characterization and understanding of host-pathogen interactions with respect to novel virulence factors of multidrug resistant and fastidious bacteria and viruses. We focus on virulence factors and biochemical pathways needed for pathogenicity that can be targeted using novel therapeutic approaches that lower the risks of developing drug resistance. Specifically, we are interested in those molecular targets with a general effect on the infection process, like those affecting attachment, biofilm formation or which simultaneously regulate multiple virulence mechanisms. We are using the opportunistic pathogen Pseudomonas aeruginosa as a model because of its versatility of virulence strategies for different hosts, which provides different models in which to examine bacterial factors important for the pathogenicity process. P. aeruginosa’s extensively studied biofilm also provides an excellent model to study factors affecting the physiology of the biofilm, which is essential for persistence and resistance to antibiotics and host defenses in the context of important diseases such as cystic fibrosis and chronic obstructive pulmonary disease.

Role of oxylipins in bacterial virulence

Currently, one of our main foci of research is the study of the oxylipins’ role in bacteria using P. aeruginosa as a model. We recently discovered that oxylipins produced by P. aeruginosa are important for biofilm formation and virulence. Oxylipin synthesis is mainly catalyzed by fatty acid dioxygenases and monooxygenases, which are widely distributed among eukaryotic organisms.

Oxylipins produced by these enzymes have diverse relevant physiological roles. For example, in mammals the best known oxylipins are the leukotrienes and prostanoids, which are implicated in inflammation, fever, pain and other physiological processes. In plants, jasmonic acid and its derivatives that mediate hormone-like effects are involved in development and in mounting defense responses. In Fungi, oxylipins participate in reproduction and pathogenesis. However, very little is known about the role of oxylipins in bacteria. Thus, we are investigating several aspects of the molecular biology and physiology of oxylipins in the context of acute and chronic infections using different animal and plant models.

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Phage therapy using engineered filamentous bacteriophages

 

Another area of active research in our laboratory focuses on the molecular biology of filamentous phages aimed at developing novel phage therapies. These bacterial viruses are peculiar in that they do not cause bacterial killing through lysis, as many other phage do. Instead, they are constantly secreted by the infected bacteria, which can be beneficial for lowering the risk of promoting phage resistance.

Currently, we are engineering the filamentous phage Pf of P. aeruginosa for the treatment of biofilm-related chronic infections with this pathogen as an adjunct to the use of antibiotics. Pf phage will be genetically manipulated in such a way that when it infects P. aeruginosa it will subvert de novo biofilm formation and induce biofilm dispersion, thus rendering the bacterium more susceptible to host immunity and antibiotics and allowing the use of lower doses of antibiotics.

Pf phage-based therapy strategy for treatment of P. aeruginosa infections.

This novel strategy shares the advantages of traditional phage therapy based on lytic phages over the use of antibiotics and additionally has the advantage of a reduced risk of positive selection for phage-resistance since bacteria are not going to be killed directly by Pf phage. Different from other therapeutic strategies, ours does not require targeting the entire population of infecting bacteria. Instead, by infecting a subpopulation of bacterial cells the modified Pf will destabilize the entire biofilm and induce its dispersion, making whole populations of bacteria susceptible to host immune defenses and antibiotic treatment.

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Identification of small molecules targeting novel virulence factors

The lab also has as a major effort in the development of therapies that target novel as yet unkown virulence factors or using novel approaches to target known virulence factors. Thus, taking advantage of Southern Research state of the art high throughput screening (HTS) capabilities, we are developing HTS assays to identify new compounds to combat multidrug resistant bacteria and viruses.


Primary HTS assay

Primary HTS assay for identification of inhibitors of oxylipins production by P. aeruginosa.

In this line of research we are developing an HTS assay for the identification of inhibitors of oxylipin production by P. aeruginosa. Since we found that blocking oxylipin production by P. aeruginosa affects its capacity to form a biofilm and significantly reduces virulence in vivo, better understanding the components of the oxylipin biosynthetic pathway has the potential to identify targets for novel drugs that will be highly effective at killing P. aeruginosa, without the risk of promoting drug resistance. In the same vein, our lab is involved in a collaborative multi center effort to identify inhibitors of the RNA-dependent RNA polymerase of the influenza A virus, also by using HTS. Targeting the polymerase instead of the viral surface proteins is expected to reduce the probability of promoting drug resistance, since the polymerase is a more highly conserved and less variable protein.

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Javier Campos-Gomez, Ph.D.

Research Biologist, Department Infectious Diseases

Javier Campos-Gomez joined Southern Research in 2012 as a research associate biologist. His main research interest is in the field of infectious diseases, where he is focused on developing bacteriophage based therapies to treat or prevent viral and bacterial infectious diseases. This includes engineering filamentous phages for targeting and containing multidrug resistant and reemerging bacterial diseases and the use of phages as platforms to display antigens of important pathogens with vaccines purposes.[ Read Full Bio Here ]

Lab Members

Eriel Martinez-Gutierrez, Ph.D.

Eriel Martinez-Gutierrez, Ph.D.

Associate Research Biologist

Eriel Martinez-Gutierrez, Ph.D., received his doctorate in molecular biology from the University of Barcelona, Spain, in 2011. He has extensive experience in the field of bacteriology and bacteriophages, with an overarching research interest in molecular biology and physiology of bacteria. He has authored several manuscripts on the molecular biology of filamentous phages in Vibrio cholerae and Pseudomonas aeruginosa.
Martinez-Gutierrez also described the unprecedented mechanism of action of a unique oleate diol synthase activity in Pseudomonas aeruginosa in prokaryotic cells. He recently described the biological function of the oxylipins derived from the oleate diol synthase activity, being the first report on the role of oxylipins in bacteria. He is currently interested in deciphering the molecular mechanism by which bacteria regulate oxylipin production and their mechanism of action.
Martinez-Gutierrez came to Southern Research from the lab of Dr. François-Xavier Barre at the National Center for Scientific Research (CNRS), France, where he completed a Postdoctoral Research Fellowship working on the molecular biology of V. cholerae filamentous phage CTXΦ.

Eric Quick

Eric Quick

Associate Research Biologist

Eric Quick, associate biologist, graduated from the University of Alabama at Birmingham (UAB) with a bachelor’s degree in molecular biology. Subsequently, in 2013, he completed a one-year Master’s in biotechnology at UAB’s School of Health Professions. Eric joined Southern Research in April 2014 and began working with HIV and Influenza entry mechanisms. Eric began working in the lab in 2015 to assist in novel research with Pseudomonas aeruginosa while continuing work with Influenza, which is his main subject of study.

Rachael ‘Kate’ Cosnahan

Rachael ‘Kate’ Cosnahan

Associate Research Biologist

Rachael ‘Kate’ Cosnahan graduated from the University of Southern Mississippi with a bachelors in microbiology. While studying at Southern Miss, she was a research and teaching assistant in the biology and chemistry departments. After graduation, she worked in industry as a microbiology quality control technician. In August 2015, she moved to Birmingham to pursue a masters in Environmental biology management at Samford University. Kate joined the Campos-Gomez lab at Southern Research in October 2016, assisting with novel Pseudomonas aeruginosa diol-synthase activities, oxylipin biosynthetic pathways and filamentous phage engineering to inhibit biofilm formation. Kate is also working alongside Mason Wu in structural biology, specifically with cell culture, protein expression and purification assays.



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