{"id":2888,"date":"2024-06-11T15:34:07","date_gmt":"2024-06-11T19:34:07","guid":{"rendered":"https:\/\/www.med.unc.edu\/microimm\/?post_type=ud_entry&p=2888"},"modified":"2026-01-20T14:03:04","modified_gmt":"2026-01-20T19:03:04","slug":"brian-conlon-phd","status":"publish","type":"ud_entry","link":"https:\/\/www.med.unc.edu\/microimm\/people\/brian-conlon-phd\/","title":{"rendered":"Brian Conlon, PhD"},"content":{"rendered":"
\n

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<\/em>. 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.<\/p>\n

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<\/em> within a biofilm.<\/p>\n

Our long-term goal is to develop a thorough understanding of how\u00a0S. aureus<\/em>\u00a0survives antibiotic treatments during infection and to develop novel antibiotic treatments to efficiently kill this pathogen and improve the treatment chronic and relapsing infections.<\/p>\n<\/div>\n

<\/div>\n
\n

Our research can be divided into 2 major topics:<\/strong><\/p>\n

\u00a01. <\/strong>The role of the innate immune system in the failure of antibiotic treatments<\/strong><\/p>\n

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<\/em> 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<\/em> 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.<\/p>\n

2. New therapeutic development<\/strong><\/p>\n

We are interested in identifying new ways of directly targeting and killing antibiotic tolerant persister cells for the rapid eradication of S. aureus<\/em> 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<\/em> 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<\/em> infection.<\/p>\n

Our long-term goal is to develop a thorough understanding of how\u00a0S. aureus<\/em>\u00a0survives antibiotic treatments during infection and to develop novel antibiotic treatments to efficiently kill this pathogen and improve the treatment chronic and relapsing infections.<\/p>\n

Selected Publications<\/h3>\n
    \n
  1. \n
    Velez A.Z., Radin J.N., Kennedy E.N., Parsons J.B., Tong H.M., Jung E., Alam E., Radlinski L.C., Wagner N.J., Fowler V.G. Jr., Rowe S.E., Kehl-Fie T.,\u00a0Conlon B.P.<\/b><\/div>\n
    The innate immune\u00a0protein calprotectin ablates the bactericidal activity of \u03b2-lactam antibiotics. Jan 20;123(3):e2513462123,\u00a0doi: 10.1073\/pnas.2513462123.\u00a0Proc Natl Acad Sci U S A<\/b>.\u00a0(2026)<\/div>\n<\/li>\n
  2. \n
    Lu K.Y., Yang X., Eldridge J.G., Wagner N.J., Hardy\u00a0B., Axtman M., Rowe S.E., Wang X., Fowler V.G., Helaine\u00a0S., Pearce K.H.,\u00a0Conlon B.P<\/b>.\u2028A host-directed adjuvant resuscitates and sensitizes intracellular bacterial persisters to antibiotics<\/i>.\u00a0Nat Microbiol.<\/i>\u00a0<\/b>Nov;10(11):3013-3025. (2025).<\/div>\n<\/li>\n
  3. \n
    Parsons J., Mourad A.,\u00a0Conlon B.P.,<\/b>\u00a0Kielian T., Fowler V.G.\u2028Methicillin-resistant and methicillin-susceptible Staphylococcus aureus: Tolerance, evasion, and treatment.\u00a0Nat. Rev\u00a0<\/i><\/b>Microbial<\/i><\/b>.\u00a0<\/i><\/b>10.1038\/s41579-025-01226-2 (2025).<\/div>\n<\/li>\n
  4. \n
    Shook J.C., Genito C.J., Darwitz B.P., Tyson K., Velez A.Z., Bridwell S.K., Parsons J.B., Rowe S.E., Marshall C.W.,\u00a0Conlon B.P*<\/u><\/b>., Thurlow\u00a0L.R*.<\/u>\u2028*co-corresponding and senior authors.\u00a0Diabetes potentiates the emergence and expansion of antibiotic resistance<\/i>.\u00a0Sci Adv<\/b>. 11(7), eadk3459 (2025).<\/div>\n<\/li>\n
  5. \n
    Host stress drives tolerance and persistence: The bane of anti-microbial therapeutics. Helaine S,\u00a0Conlon\u00a0BP<\/b>, Davis KM, Russell DG.\u00a0Cell Host & Microbe<\/i><\/b>, 32 (6), 852-862, (2024).<\/div>\n<\/li>\n
  6. \n
    In-patient evolution of a high-persister\u00a0Escherichia coli<\/i>\u00a0strain with reduced in-vivo antibiotic susceptibility. Parsons JB, Sidders AE, Velez AZ, Hanson BM, Ruffin F, Rowe SE, Arias CA, Fowler VG, Thaden JT,\u00a0Conlon BP<\/b>.\u00a0Jan 16;121(3):e2314514121.\u00a0Proc Natl Acad Sci U S A.<\/b>\u00a0(2024).<\/div>\n<\/li>\n
  7. \n
    Reactive oxygen species induce persister formation during systemic\u00a0Staphylococcus aureus<\/i>\u00a0infection.Rowe SE, Wagner N, Li L, Beam JE, Wilkinson AD, Radlinski LR, Zhang Q, Miao EA and\u00a0Conlon BP<\/b>.\u00a0Nat\u00a0<\/i><\/b>Microbial.<\/i><\/b>\u00a0Feb;5(2):282-290, (2020).<\/div>\n<\/li>\n
  8. \n
    Chemical Induction of Aminoglycoside Uptake Overcomes Antibiotic Tolerance and Resistance in\u00a0Staphylococcus aureus<\/i>.\u00a0Radlinski L., Rowe SE., Brzozowski R., Wilkinson A., Huang R., Eswara, P., and\u00a0<\/i>Conlon BP<\/b>.\u00a0<\/i>Cell Chem.\u00a0<\/i><\/b>Biol.<\/i><\/b>, S2451-9456(19)30240-5, (2019).<\/div>\n<\/li>\n
  9. \n
    Pseudomonas aeruginosa<\/i>\u00a0exoproducts determine antibiotic efficacy against\u00a0Staphylococcus aureus<\/i>. Radlinski L, Rowe SE, Kartchner L, Maile R, Cairns BA, Vitko NP, Gode CJ, Lachiewicz AM, Wolfgang MC and\u00a0Conlon BP<\/b>.\u00a0PLoS Biology<\/i><\/b>, 15(11) e2003981, (2017).<\/div>\n<\/li>\n
  10. \n
    Persister formation in\u00a0Staphylococcus aureus<\/i>\u00a0is associated with ATP depletion.\u00a0Conlon BP<\/b>, Rowe SE, Brown-Gandt AV, Nuxoll AS, Clair G, Donegan NP, Adkins JN, Cheung AL, Lewis K.\u00a0Nature Microbiology<\/i>. 1, 16051, (2016).<\/div>\n<\/li>\n<\/ol>\n<\/div>\n","protected":false},"featured_media":2889,"menu_order":0,"template":"","format":"standard","meta":{"_acf_changed":false,"layout":"","cellInformation":"","apiCallInformation":"","_links_to":"","_links_to_target":""},"ud_division":[19,21],"class_list":["post-2888","ud_entry","type-ud_entry","status-publish","format-standard","has-post-thumbnail","hentry","ud_division-microbial-interactions","ud_division-primary","odd"],"acf":[],"yoast_head":"\nBrian Conlon, PhD - Microbiology and Immunology<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.med.unc.edu\/microimm\/people\/brian-conlon-phd\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Brian Conlon, PhD - Microbiology and Immunology\" \/>\n<meta property=\"og:description\" content=\"Antibiotic tolerance and antibiotic resistance are major challenges, resulting in growing numbers of deaths worldwide each year. 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