The Rumbaugh Lab

Polymicrobial interactions and Biofilm Formation in Chronic Wounds
The impact of wound infections on our healthcare system is enormous. In fact, chronically-infected diabetic foot ulcers are considered the most significant wound care problem in the world. One major reason that these infections are so difficult to treat is because bacteria develop ‘biofilms’ after they colonize wounds. A biofilm is a slimy, sugar-rich structure that encases bacteria and protects them from the immune response and antimicrobials, making them up to 1,000 times less susceptible to killing. The microbial populations of chronic wounds are complex and can include dozens of major species, yet very little is understood how interactions between these species influence the course of infection or affect therapeutic success. We have developed polymicrobial wound models in order to investigate how different species in wounds work together to build better biofilms and create more difficult to treat infections.

Pseudomonas aeruginosa Pathogenesis in Wounds
Infection with the Gram-negative pathogen Pseudomonas aeruginosa is one of the major causes of morbidity and mortality in severely burned patients, and the cause of debilitating chronic infections in diabetic patients. P. aeruginosa relies on an arsenal of cell-associated and secreted virulence factors to colonize and infect its host, and it persists and invades the immune system by building biofilms.

In collaboration with Marvin Whiteley’s group, http://whiteleylab.biosci.gatech.edu/?q=home, we are using advanced genomic approaches to understand the pathogenesis of P. aeruginosa in human wounds and mouse models that recapitulate disease.

Necrotizing Soft Tissue Infections
Necrotizing soft tissue infections (NSTIs) are a group of infections that are rapidly progressive and require immediate surgical intervention. The pathogenesis and microbiology of these infections are understudied, which partially explains the relatively stagnant and high mortality despite aggressive surgical and medical treatments. We have recently shown through human metagenomics studies that obligate anaerobes are abundant in NSTIs and are associated with a worsened prognosis. Currently, we are focused on better understanding the polymicrobial interactions behind NSTIs through the study of model organisms, Staphylococcus aureus and Bacteroides fragilis. We hypothesize that microbial interactions that contain obligate anaerobes cause a worsened NSTI compared to those with facultative anaerobes alone.

Development of Biofilm Degrading Agents
Biofilms are communities of microorganisms protected by a thick, self-synthesized extracellular matrix of polysaccharides, proteins, lipids and extracellular DNA. As much as 85% of all bacterial infections are biofilm-associated, compounding the problem of rising antibiotic resistance by offering the resident microbes greatly increased tolerances to antimicrobials. We are tackling this problem by developing agents that degrade the protective extracellular matrix, thereby augmenting the effectiveness of existing antimicrobial agents. We have shown that biofilm polysaccharides can be degraded by enzymes that hydrolyze the glycosidic bonds between the individual sugar moieties, thereby causing the structural collapse of the biofilms, and potentiating the action of antibiotics against the newly liberated bacterial cells in vivo. Currently, we are working on optimizing enzymatic to break down the biofilms present in complex, polymicrobial, clinical infections in a broad-spectrum manner. In doing so, we hope to be able to create a widely-applicable topical treatment that can greatly increase the effectiveness of existing antibiotics, reversing some of the devastating effects of antibiotic resistance on the healthcare field.

Preclinical Efficacy Testing of Experimental Antimicrobials
We have developed several in vitro and in vivo wound models with which to test experimental antimicrobials and anti-biofilm agents. We have extensive experience in working with companies and academic collaborators to test the efficacy of new therapeutics.

Interkingdom signaling between P. aeruginosa Quorum Sensing Molecules and Host Cells
Quorum sensing (QS) is a cell density-dependent signaling process used by many bacteria to coordinate gene expression in a population. QS in Gram-negative bacteria is controlled by diffusible molecules called autoinducers (AI) that function as ligands for regulatable transcription factors. At least two separate QS systems exist in P. aeruginosa, the LasI/LasR and RhlI/RhlR systems. The ligands for LasR and RhlR are N-3-oxododecanoyl- and N-butyryl- homoserine lactones, or PAI-1 and PAI-2, respectively. Several studies indicate that bacterial autoinducers, and PAI-1 in particular, can also influence gene expression in host eukaryotic cells, a process we’ve termed interkingdom signaling. We hypothesize that this regulatory process involves autoinducer receptor molecules in the host cells, possibly transcription factors. We have shown that P. aeruginosa autoinducers can efficiently enter mammalian cells and modulate gene expression potentially through the interaction of nuclear hormone receptors. In addition, we have also recently shown that the nematode C. elegans can sense bacterial autoinducers and use this sensory information to ‘learn’ to avoid pathogens.

View the most recent publications here.

• Career Crossroads Lead to Research Triumph
• Rumbaugh Named Fellow by American Academy of Microbiology
• NIH Grant to Aid Rumbaugh’s Biofilm Dispersal Research
• Rumbaugh’s Research Yields Possible Biomarker and More Effective Biofilm Dispersal
• Rumbaugh Named 2023 Fellow by American Association for the Advancement of Science