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Associate Professor
6209 Marsico Hall

Research

Antibiotic tolerance and antibiotic resistance are major challenges, resulting in growing numbers of deaths worldwide each year. The Conlon Lab focuses on antibiotic tolerance and resistance in the infection microenvironment. Here, nutrient availability, interactions between the pathogen and the host, as well as co-infecting or commensal microorganisms can have a major impact on antibiotic tolerance and the evolution of antibiotic resistance. Using mice to model numerous infection types including a diabetic wound, a skin and soft tissue infection and bacteremia, we aim to identify drivers of antibiotic success or failure, with a focus on one of the most important human pathogens, Staphylococcus aureus. Developing an understanding of the determinants of treatment success or failure then facilitates translational projects to augment the microenvironment, improve antibiotic efficacy and eradicate infection.

We are also interested in the development of novel approaches to target and kill bacteria that have entered a low metabolic state, for example, S. aureus within a biofilm.

Our long-term goal is to develop a thorough understanding of how S. aureus survives antibiotic treatments during infection and to develop novel antibiotic treatments to efficiently kill this pathogen and improve the treatment chronic and relapsing infections.

Our research can be divided into 2 major topics:

 1. The role of the innate immune system in the failure of antibiotic treatments

The impact of various components of the innate immune response on antibiotic efficacy in patients remains largely unknown. We find that in murine bacteremia, large reservoirs of S. aureus can survive antibiotic treatment in a variety of tissues. We also find that this survival is induced, at least in part, by host produced reactive oxygen species (ROS) that inhibit bacterial central metabolism and induce an antibiotic tolerant state. We further find that reducing ROS by genetic manipulation of the mice or application of an antioxidant results in improved antibiotic efficacy, thereby demonstrating that ROS, a major component of the innate immune response, are antagonistic to antibiotic efficacy in vivo. We aim to further investigate the mechanism of ROS induced tolerance while examining the feasibility of developing new host-targeted therapeutics to restore antibiotic susceptibility during infection. We are also interrogating other aspects of S. aureus host interaction that induce an antibiotic tolerant state with a goal towards identifying new therapeutic options to unleash the bactericidal activity of antibiotics during infection.

2. New therapeutic development

We are interested in identifying new ways of directly targeting and killing antibiotic tolerant persister cells for the rapid eradication of S. aureus populations. We have identified numerous methods to kill persister cells and we are continuing to pursue these methods for the development of anti-persister therapeutics, capable of rapidly eradicating S. aureus in vivo. These approaches include the targeting of the membrane to sensitize bacteria to standard of care antibiotics. We believe that developing novel therapeutics to target the antibiotic tolerant state will lead to novel therapeutics capable of more efficiently and effectively treating S. aureus infection.

Our long-term goal is to develop a thorough understanding of how S. aureus survives antibiotic treatments during infection and to develop novel antibiotic treatments to efficiently kill this pathogen and improve the treatment chronic and relapsing infections.

Publications

Inflammasome-mediated glucose limitation induces antibiotic tolerance in Staphylococcus aureus. Beam JE, Wagner NJ, Lu KY, Rowe SE, Conlon BP, iScience, (2023).

Antibiotic-induced accumulation of lipid II sensitizes bacteria to antimicrobial fatty acids. Sidders AE, Kedziora KM, Beam JE, Bui DT, Parsons JB, Rowe SE, Conlon BPELife, (2023).

Lu KY, Wagner NJ, Velez AZ, Ceppe A, Conlon BP, Muhlebach MS. Antibiotic Tolerance and Treatment Outcomes in Cystic Fibrosis Methicillin-Resistant Staphylococcus aureus Infections. Microbiology Spectrum, (2023).

The use of acute immunosuppressive therapy to improve antibiotic efficacy against intracellular Staphylococcus aureus, Beam JE, Wagner NJ, Rowe SE, Bahnson EM, Conlon BP. In print. Microbiology Spectrum, (2022).

Negrón O, Hur WS, Prasad J, Paul DS, Rowe SE, Degen JL, Abrahams SR, Antoniak S, Conlon BP, Bergmeier W, Hӧӧk M, Flick MJ. Fibrin(ogen) engagement of S. aureus promotes the host antimicrobial response and suppression of microbe dissemination following peritoneal infection. PLoS Pathogens, (2022).

Beam JE, Rowe SE, Conlon BP. Shooting yourself in the foot: How immune cells induce antibiotic tolerance in microbial pathogens. PloS Pathogens, (2021).

Beam JE, Wagner NJ, Shook JC, Bahnson SM, Fowler VG, Rowe SE and Conlon BP. Macrophage-Produced Peroxynitrite Induces Antibiotic Tolerance and Supersedes Intrinsic Mechanisms of Persister Formation, Infection & Immunity, (2021)

Durham PG, Sidders AE, Beam JE, Kedziora KM, Dayton PA, Conlon BP, Papadopoulou V and Rowe SE. Harnessing Ultrasound-Stimulated Phase Change Contrast Agents to Improve Antibiotic Efficacy Against Methicillin-Resistant Staphylococcus aureus Biofilms, Biofilms (2021).

Rowe SE, Beam JE and Conlon BP. Recalcitrant Staphylococcus aureus Infections: Obstacles and Solutions. Infection and Immunity, (2021).

Rowe SE, Wagner N, Li L, Beam JE, Wilkinson AD, Radlinski LR, Zhang Q, Miao EA and Conlon BP. Reactive oxygen species induce persister formation during systemic Staphylococcus aureus infection. Nature Microbiology, (2020).

Griffith, E ; Zhao, Y; Singh, A; Conlon, BP; Tangallapally, R; Shadrick, W; Liu, J; Wallace, M; Yang, L; Elmore, J; Li, Y; Zheng, Z; Miller, D ; Cheramie, M; Lee, R; LaFleur, M D.; Lewis, K  ; Lee, R., Ureadepsipeptides as ClpP Activators, ACS Infectious Diseases, (2019).

Zalis E, Nuxoll A, Manuse S, Clair G, Radlinski L, Conlon BP, Adkins JA, and Lewis K. Stochastic variation in expression of the TCA cycle produces persister cells. mBio, (2019).

Gilbertie JM, Schnabel LV, Hickok NJ, Jacob ME, Conlon BP, Shapiro IM, Parvizi J, Schaer TP.  Equine or porcine synovial fluid as a novel ex vivo model for the study of bacterial free-floating biofilms that form in human joint infections. PloS One. Epub. (2019).

Radlinski L., Rowe SE., Brzozowski R., Wilkinson A., Huang R., Eswara, P., and Conlon BP. Chemical Induction of Aminoglycoside Uptake Overcomes Antibiotic Tolerance and Resistance in Staphylococcus aureus. Cell Chemical Biology, (2019).

Radlinski L, Rowe SE, Kartchner L, Maile R, Cairns BA, Vitko NP, Gode CJ, Lachiewicz AM, Wolfgang MC and Conlon BP.  Pseudomonas aeruginosa exoproducts determine antibiotic efficacy against Staphylococcus aureus. PLoS Biology, (2017).

Radlinski L and Conlon BP, Antibiotic susceptibility in the complex infection environment. Current Opinions in Microbiology, (2017).

Bui LM, Conlon BP, Kidd SP. Antibiotic tolerance and the alternative lifestyles of Staphylococcus aureus. Essays in Biochemistry, (2017).

Shan Y, Brown-Gandt A, Rowe SE, Deisinger JP, Conlon BP, Lewis K. ATP-Dependent Persister Formation in Escherichia coli. MBio. (2017).

Waters EM, Rowe SE, O’Gara JP, Conlon BP. Convergence of Staphylococcus aureus persister and biofilm research: Can biofilms be defined as communities of adherent persister cells? PLos Pathogens. (2016).

Homma T, Nuxoll A, Brown Gandt A, Ebner P, Engels I, Schneider T, Götz F, Lewis K and Conlon BP Dual targeting of cell wall precursors by teixobactin leads to cell lysis. Antimicrobial Agents & Chemotherapy. (2016).

Conlon BP, Rowe SE, Brown-Gandt AV, Nuxoll AS, Clair G, Donegan NP, Adkins JN, Cheung AL, Lewis K. Persister formation by ATP depletion. Nature Microbiology. (2016).

Ling LL, Schneider T, Peoples AJ, Spoering AL, Engels I, Conlon BP, Hughes DE, Epstein S, Jones M, Poullenec K, Steadman V, Cohen DR, Felix CR, Fetterman KA, Millett WP, Nitti AG, Zullo AM, Chen C, Lewis K Killing of pathogens by teixobactin without associated resistance. Nature. (2015).

Rowe SE, Conlon BP, Keren I, and Lewis K Bacterial Persistence. Methods in Molecular Biology. (2015).

Conlon BP, Rowe SE, Lewis K (2014) Persister cells in biofilm associated infection. Biofilm-based Healthcare Associated Infections. (2014).

Lewis K, Conlon BP, LaFleur MD. Eradication of Dormant Pathogens. Antibiotics: Current Innovations and Future Trends. (2014).

Conlon BP, Geoghegan JA, Waters EM, McCarthy H, Rowe SE, Davies JR, Schaeffer CR, Foster TJ, Fey PD, O’Gara JP. A role for the A domain of unprocessed accumulation associated protein (Aap) in the attachment phase of the Staphylococcus epidermidis biofilm phenotype. Journal of Bacteriology. (2014).

Conlon BP Staphylococcus aureus chronic and relapsing infections: Evidence of a role for persister cells. Bioessays. (2014).

Conlon BP, Nakayasu EN, Fleck LE, LaFleur MD, Isabella VM, Coleman K, Leonard SN, Smith RD, Adkins JN, Lewis K. Activated ClpP kills persisters and eradicates a chronic biofilm infection. Nature. (2013)

Holland LM, Conlon BP, O’Gara JP Mutation of tagO reveals an essential role for wall teichoic acids in Staphylococcus epidermidis biofilm development. Microbiology. (2010).

Brian Conlon