In Press: Dr. Armand Brown Publishes First Author Paper in American Society for Microbiology’s mBio
Dr. Armand Brown is currently a postdoctoral fellow in the Department of Microbiology & Molecular Genetics at The University of Texas Health Science Center at Houston (UTHealth). He graduated with a Ph.D. in Microbiology and Immunology in 2014.
His first author publication, “Antifungal Activity of the Enterococcus faecalis Peptide EntV Requires Protease Cleavage and Disulfide Bond Formation” was published in the July/August 2019 issue of American Society for Microbiology’s mBio.
What is your research about?
My research in the laboratory has been focused on studying the interkingdom interactions between the human commensal Gram positive bacterium Enterococcus faecalis, and the human commensal fungus Candida albicans. Our interest in investigating these two organisms stems from the fact that they inhabit similar anatomical niches throughout the human body, are commonly coisolated during infection, and are increasingly the cause of difficult-to-treat infections in susceptible populations. In fact, Vancomycin Resistant Enterococcus (VRE), and fluconazole-resistant Candida are both listed as serious public health threats by the CDC. Therefore, new or alternative therapies are needed to combat these types of antimicrobial resistant infections. In previous work, we discovered that E. faecalis secretes a bacteriocin known as EntV that we determined suppresses C. albicans pathogenesis. We then set out to determine how EntV is post-translationally processed in order to understand the mechanism of its formation such that we could develop EntV as a potential therapy. In this report, we provide the mechanism of its processing, and provide a role for a previously uncharacterized enterococcal disulfide bond forming protein (known as DsbA) in its formation. Briefly, we determined that DsbA is required for the activity and function of EntV by catalyzing the requisite disulfide bond within it. This is interesting considering that this mechanism (oxidative protein folding) has been generally thought to be a mechanism not used by Firmicutes, such as E. faecalis for protein function or stability. Our results challenge this dogma. We hypothesize that in addition to EntV, DsbA is likely required for the function of other enterococcal proteins, some of which may be important for fitness and pathogenicity.
Why is this important for the public?
This is important to the public for a couple of reasons. We are now one step closer towards our goal of developing EntV as a potential therapy for fungal infections. In addition, it is important, because we have identified a role for a protein that was previously thought to be nonessential, and in fact may play a greater role in E. faecalis and other Firmicutes fitness and pathogenicity. Furthermore, DsbA may allow us to identify additional targets for therapeutic intervention against enterococcal infections.
Why are you passionate about this project?
I am passionate about this project because it ties together my various research interests into one project. As a graduate student and postdoctoral fellow, I have focused much of my energy on becoming an expert within the Gram-positive bacteriology field while studying clinically relevant infections. In addition, I have always been interested in developing novel therapies for antimicrobial resistant organisms. I am happy to say that while investigating additional roles for DsbA, I made an exciting discovery. I am now working to transition these findings into an independent project as a Principal Investigator. I’m keeping my fingers crossed and hoping that all continues to go well.
I know that your paper was an editor’s pick article. What does that mean and why is this important?
Editor’s pick articles are articles selected by the editor-in-chief to be noteworthy or of high interest for people within the field.
Have a question for Armand? Ask him at www.gsbsalumni.com. In Press is a section in The Pipette Gazette that highlights publications by students. To read more In Press articles, click here.