The Problem

The Frank Lab studies relationships between bacterial pathogens and their hosts in biofilm-associated infections. Biofilms are organized communities of microbes attached to a surface, or to each other, and are encased in a self-produced extracellular matrix. Biofilm growth provides protection from adverse environmental conditions, enables evasion of the host immune defenses, and confers resistance to remarkably high concentrations of antimicrobial agents. Pathogenic bacteria can form biofilms on surfaces throughout a host and on virtually any implantable medical device. Examples of biofilm infections include infective endocarditis, wound infection, prosthetic joint infection, intravascular catheter infection, and chronic otitis media. Biofilm infections pose a significant challenge to human health because of their chronic nature and the difficulty associated with treating them. Our lab is interested in understanding how biofilms form, which will ultimately allow us to develop new therapies to treat biofilm-associated infections.

The Frank Lab's current efforts focus on Enterococcus faecalis, a Gram-positive bacterium that is both a human commensal and an opportunistic pathogen. Enterococci are exceptionally robust, recalcitrant to many classes of antimicrobial agents, and highly proficient at acquiring virulence factors and additional antibiotic resistance genes via horizontal gene transfer. These characteristics have enabled E. faecalis and other enterococci to emerge as leading causes of healthcare-associated infections. In immunosuppressed patients, E. faecalis can cause a myriad of infections with biofilm etiology, including endocarditis, surgical site infections, and catheter-associated urinary tract infections. Enterococci also pose a major health threat to wounded soldiers, as Enterococcus species are the bacteria that are most commonly isolated from combat extremity wound infections.

our Approach

The Frank Lab pairs animal models of biofilm formation with genetic, molecular, genomic, imaging  and biochemical approaches to address the following overall research areas:

(1) Define sensing pathways and regulatory circuits that are involved in triggering transcriptional and stress responses in E. faecalis when it is causing biofilm infections in a host.

(2) Identify new biofilm-associated virulence factors in E. faecalis and determine how they affect interactions between the bacterium and its host during infection.

(3) Test new methods to remove biofilms and prevent their formation.

(4) Elucidate mechanisms by which E. faecalis colonizes endovascular tissues as part of a broader interest in understanding how biofilm-forming bacteria may affect human cardiovascular health.



“Understanding the complex genetic regulatory networks that control the transition of pathogenic bacteria from planktonic growth to biofilm growth may lead to the successful development of new strategies to treat or prevent biofilm infections.”


Dr. Frank’s postdoctoral work at the University of Minnesota identified that a membrane metalloprotease called Eep is an important virulence factor contributing to E. faecalis biofilm-associated infection in rabbit endocarditis and mouse catheter-associated urinary tract models, but not in a rat model of foreign body osteomyelitis. Imaging studies indicated that the function of Eep in biofilm formation may affect the bacterial cell surface and the biofilm matrix. These studies served as the foundation for several of the research projects that are now underway in Dr. Frank’s lab at USU.

The stringent response is a stress response that is well-conserved among bacteria and is activated during periods of nutritional deprivation and other conditions that are unfavorable for growth. The stringent response is activated upon accumulation of the small molecule (p)ppGpp. Dr. Frank previously discovered that E. faecalis cells enter a stringent response-like state in a rabbit foreign body abscess model and showed that E. faecalis mutants with varying levels of (p)ppGpp differentially survived in abscesses. Recent work by Dr. Frank and her collaborators demonstrated that differential basal levels of (p)ppGpp, rather than the activation of the stringent response, affect processes that contribute to the pathogenesis of E. faecalis infective endocarditis.

Work initiated in Dr. Frank’s lab at USU led to the discovery that the antibacterial enzyme lysozyme, which is an important component of the human innate immune system, exerts bactericidal activity against E. faecalis biofilm cells. The in vitro data we have collected thus far indicate that lysozyme has the potential to be developed into a novel therapeutic for biofilm-associated infections caused by multidrug resistant bacteria. A patent application derived from this discovery was filed recently, and a manuscript is in preparation for submission.

Manuscript in preparation.