Research Statement

The Centers for Disease Control and Prevention has labelled bacterial antimicrobial resistance (AMR) a global threat [1] due to the consistent increase in yearly AMR-associated human cases [2,3]. AMR is most concerning in six “ESKAPE” bacteria (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) due to their role in hospital-acquired infections [4]. However, AMR in non-pathogenic bacteria is also concerning as these bacteria have been shown to be a reservoir for AMR genes, which can be horizontally transferred into human pathogens [5,6]. While being extremely useful traditional antimicrobial compounds are typically non-specific and target a wide range of microbes, including beneficial bacteria, depending on their mechanism of action [7]. The emergence of high throughput sequencing techniques and utilization of CRISPR-Cas systems has allowed for a more specific targeting of bacteria carrying specific genes or sequences [8].

During my graduate career I worked with the foodborne human pathogen Listeria monocytogenes, which is notorious for its ability to persist in food processing facilities due to its antimicrobial resistance, resistance to cold temperatures and ability to form biofilms [9]. It can also cause serious illness in humans due to its ability to cross the blood-brain and placental-neonatal barriers [10]. I studied antimicrobial reistance in L. monocytogenes and the use of bacteriophage as an alternative antimicrobial agent against hypervirulent L. monocytogenes strains. I investigated bacteriophage resistance prevalence and the genetic determinants responsible for bacteriophage resistance in L. monocytogenes. Through the use of high-throughput screening and whole-genome sequence analysis I was able to determine common bacteriophage resistance mechanisms and how they were distributed across the L. monocytogenes species, which harbors an large amount of genetic diversity. This information is crucial to understand when developing and deploying bacteriophage as an antimicrobial, either as a therapeutic or to decontaminated surfaces in hospitals or food processing facilities.

Since joining the NCSU Biotechnology Program, and working predominantly with undergraduate students, I have shifted my focus to the opportunistic human pathogen Serratia marcescens, which you may recognize as the pink residue found in bathrooms. I have also moved from the use of native bacteriophage as an antimicrobial to bacteriophage equipped with CRISPR-Cas systems in order to increase the efficiency of cell killing while also circumventing the typical phage lytic cycle, which controls the spread of these phage into the environment.