Bruce R. Levin

Some recognized prejudices (aphorisms?):

'Doing research in population biology without mathematical and/or computer simulation models is like playing tennis without a net or boundary lines.’ (Stolen with modification from Robert Frost)

'Data may be a crutch for the insecure, but really self-confident scientists subject their hypotheses to tests that can reject them.'

'Just because a project may be useful, doesn't mean it's not interesting, high-quality and delicious to work on Science.'

'For us, natural and not-so-natural selection is about dN/dt and not dN/dS.'

‘All models and model systems are wrong, some are useful.’ (Borrowed with a "friendly amendment” from George Box)

‘Models can be more useful when they don’t fit the data than when they do. That means that there are errors in the biological assumptions upon which the model is based, and ideally point to where those errors are and how they should be modified.’

'Eukaryotes are great to sleep with, but bacteria are far better for research.'

Our research includes mathematical and computer simulation modeling and experiments on the population and evolutionary biology of bacteria and their viruses and accessory genetic elements. While some of our research addresses purely academic ecological and evolutionary questions, the primary focus of our research is the application of the theory and methodology of population and evolutionary biology to health-related issues. The following is a list of the projects on which we are currently working, recently initiated (*) or recently completed (**) (October 2024) and the names of the primary investigator(s) involved in these studies.   If you want information about these ongoing studies, you are welcome to write to me (blevin@emory.edu), or by clicking on the names of the other people working on these projects..

1. A population dynamic study of Crispr-Cas in protecting Staphylococcus aureus from phage. With Alysha Ismail,  Andrew Smith, Brandon Berryhill, Teresa Gil Gil, Eduardo Roman, Luciano Marraffini, and Bruce Levin.

2. A theoretical and experimental study of heteroresistance to antibiotics. With Teresa Gil Gil, Brandon Berryhill, Joshua Manuel, Andrew Smith, Dan Andersson, Fernando Baquero, David Weiss, and Bruce Levin.

3. Generality of the evolution of heteroresistance upon the long-term exposure to bacteriostatic antibiotics. With Teresa Gil Gil, Brandon Berryhill, Joshua Manuel, Andrew Smith, Dan Andersson, Fernando Baquero, David Weiss, and Bruce Levin.

4. Maximizing joint antibiotic and phage therapy using the Galleria mellonella model system. With Brandon Berryhill, Teresa Gil Gil, Andrew Smith, Danielle Steed, and Bruce Levin.

5. An exploration of the role of phagocytosis in controlling bacterial infections: mathematical models and experiments with Staphylococcus aureus infections in wax moths, Galleria mellonella. With David Goldberg, Brandon Berryhill, Teresa Gil Gil, Nic Vega, Roland Regoes, Christopher Witzany, and Bruce Levin.

6. The population and evolutionary dynamics of bacteriophages in physically structured communities With Andres Valdez, Igor Aronson, Eduardo Roman, and Bruce Levin

7. ** An investigation into the role of antibiotic subinhibitory concentrations on mutation rates, persistence, and bacterial growth dynamics With Alysha Ismail, Teresa Gil Gil, Brandon Berryhill, Joshua Manuel, Andrew Smith, and Bruce Levin.

8. Investigating the role of bacteriophages in determining the densities and distribution of bacterial strains within the gut microbiome. With Sarah Forsstrom, Kylie Burke, Jacob Fontaine, Brandon Berryhill,  Teresa Gil Gil, Michael Woodworth, Kostas Konstantinidis, Catherine Brink, and Bruce Levin.

9. ** Employing lambda phage as a proxy for pathogens to evaluate the efficacy of infection prevention methods in clinical settings. With Kylie Burke, Brandon Berryhill, Paige Gannon, Colleen Kraft, and Joel Mumma.

10.** A study of the population and evolutionary dynamics of abortive infection as a mechanism to protect bacterial populations from phage predation. With Brandon Berryhill,  Joshua Manuel, Eduardo Roman, , and Bruce Levin.

11. ** Evaluating the policies and procedures to protect healthcare workers at Emory Hospital’s Serious Communicable Diseases Unit. With Brandon Berryhill, Kylie Burke, Andrew Smith, Jill Morgan, and Colleen Kraft.

13. A study of the mechanisms responsible for the success of fecal microbiota transplantations. With Sarah Forsstrom, Brandon Berryhill,  Teresa Gil Gil, Danielle Steed, Michael Woodworth, and Bruce Levin.

15. A study of the selective forces responsible for the evolution of toxin-mediated virulence of bacteria. With Peyton Panos, Brandon Berryhil, lTeresa Gil Gil, and Bruce Levin.

16.** A perspective on the role of the contribution of short-sighted evolution to the virulence of bacteria. With Pauline Scanlan, Fernando Baquero, and Bruce Levin.

17. * The joint action of antibiotics and bacteriophage for the treatment of prosthetic joint infections.  With Teresa Gil Gil, Skye Nash,  Michael Woodworth, Colleen Kraft, and Bruce Levin

18. A study of nutrient availability and the dynamics of phage infection and rates of mutation. Turner MacInnis, Alysha Ismail, Teresa Gil-Gil, Brandon Berryhill, and Bruce Levin

19. * The joint action of bacteriophage and antibiotics in treating urinary tract infections with E. coli.  Serena Singh, Alysha Ismail, Teresa Gil-Gil and Bruce Levin

Relatively recent publications and soon-to-be publications from our Lab: For an almost complete list of our articles, click on "Publications":

• Berryhill, B.A, T. Gil-Gil, C. Witzany. D. A, Goldberg, N.M. Vega, R,Regoes, and B.R. Levin (2024) The role of innate immunity, antibiotics, and bacteriophages in the course of bacterial infections and their treatment PDF Supplemental Material PDF

• Gil-Gil, T., B.A. Berryhill (2024) Antibiotic killing of drug-induced bacteriostatic cells. PDF

• Scanlon, P.D., F. Baquero, B.R. Levin. (2024) Short-sighted evolution of virulence for invasive gut microbes: from hypothesis to tests.(In Press, PNAS) PDF

• Ismail, A.S., B.A., Berryhill, T. Gil-Gil, J.A. Manuel, A.P. Smith, F. Baquero, B.R. Levin. (2024) The Tradeoffs Between Persistence and Mutation Rates at Sub-Inhibitory Antibiotic Concentrations in Staphylococcus aureus. (Submitted) PDF Supplemental Materials (PDF)

• Berryhill, B.A., K.B. Burke, J. Fontaine, C.E. Brink. M.G. Harvill, D.A. Goldberg, K.T. Konstantinidis, B. R. Levin, M.H. Woodworth. (2023) O Antigen Mediated Bacteriophage Resistance in Enteric Escherichia coli Populations (Submitted) PDF

• Berryhill, B.A., K.B. Burke, A.P. Smith, J.S. Morgan, J. Tarabay, J. Mamora, J.B. Varkey, J.M. Mumma, C.S. Kraft. (2024) A Bacteriophage-based Validation of a Personal Protective Equipment Doffing Procedure to be Used with High Consequence Pathogens. Infection Control and Hospital Epidemiology. DOI: https://doi.org/10.1017/ice.2024.84 PDF Supplemental Materials (PDF)

• Levin, B.R., B.A. Berryhill, T. Gil-Gil, J.A. Manual, A.P. Smith, J.E. Choby, D.I. Andersson, D.S. Weiss, F. Baquero. (2024) Theoretical Considerations and Empirical Predictions of the Pharmaco- and Population Dynamics of Heteroresistance. PNAS. DOI: https://doi.org/10.1073/pnas.2318600121 PDF Supplemental Material (PDF) Supplemental Figure 3 (PDF)

• Rodriguez-Roman, E. J.A. Manuel, D.A. Goldberg, B. R, Levin. (2024) The contribution of abortive infection to preventing populations of Lactococcus lactis from  succumbing to infections with bacteriophage. PLoS One. DOI: 10.1371/journal.pone.0298680. PDF Supplemental Material (PDF)

• Baquero, F. J. Rodriguez Beltran, B.R. Levin. (2024) Bacteriostatic cells instead of bacteriostatic antibiotics?  MBio. DOI: 10.1128/mbio.02680-23. PDF

• Banh, D.V., C.G. Roberts, A. Morales-Amador, B.A. Berryhill, W. Chaudhry, B.R. Levin, S. F. Brady, L.A. Marraffini. (2023) Bacterial cGAS senses a viral RNA to initiate immunity. Nature. DOI: 10.1038/s41586-023-06743-9PDF . PDF

• Gil-Gil, T., B.A. Berryhill, J.A. Manuel, A.P. Smith, I.C. McCall, F. Baquero, B.R. Levin. (2024) The Evolution of Heteroresistance via Small Colony Variants in Escherichia coli Following Long Term Exposure to Bacteriostatic Antibiotics. Nature Communication: https://doi.org/10.1038/s41467-024-52166-z PDF Supplemental Material (PDF)

• Burke, K.B., B.A. Berryhill, R. Garcia, D.A. Goldberg, J.A. Manuel, B.R. Levin, C.S. Kraft, J.M. Mumma. (2023) A methodology for using Lambda phages as a proxy for pathogen transmission in hospitals.  Journal of Hospital Infection. DOI: doi.org/10.1016/j.jhin.2023.01.004. PDF

• Berryhill, B.A., R. Garcia, I. McCall, W. Chaudhry, M-A. Petit, B.R. Levin (2023) The book of Lambda does not tell us that naturally occurring lysogens of Escherichia coli are likely to be resistant as well as immune. PNAS 2023 Vol. 120 No. 11 e2212121120. PDF

• Berryhill B.A., T. Gil-Gil, J.A. Manuel, A.P Smith, E. Margolis, F. Baquero,  B.R. Levin. (2023) What’s the matter with MICs: The contribution of nutrients and limiting resources to the pharmacodynamics of antibiotics and bacteria. Spectrum Microbiology doi: 10.1128/spectrum.04091-22 PDF

• Berryhill B.A., J.A. Manuel, R. Garcia, B.R. Levin. (2023) The ecological consequences and evolution of retron-mediated suicide as a way to protect Escherichia coli from being killed by phage. PLoS ONE 18(5): e0285274. https://doi.org/10.1371/journal.pone.0285274. PDF

• Berryhill, B.A., I.C. McCall, D. Huseby, D. Hughes, and B.R. Levin. (2021) Joint antibiotic and phage therapy: addressing the limitations of a seemingly ideal phage for treating Staphylococcus aureus infections. PNAS https://doi.org/10.1073/pnas.2008007118 PDF Supplemental Material PDF

• Rodríguez-Beltrán, J, R. León-Sampedro, C. de la Vega, F. Baquero, B.R. Levin and A, San Millán,  Translational demand is not a major source of plasmids-associated fitness costs (2021) Philosophical Transactions R. Soc. B 377: 20200463 PDF

• Westra, E and B.R. Levin (2020) How important is CRISPR-Cas for protecting natural populations of bacteria against infections by mobile genetic elements?| www.pnas.org/cgi/doi/10.1073/pnas.1915966117 PNAS Main Manuscript PDF, Supplemental Material PDF

• Baquero, F. and B.R. Levin (2020) Proximate and ultimate causes of the bactericidal action of antibiotics. Nature Reviews Microbiology 19: 123–132 PDF

• Chaudhry, W.N., E. Lee, A. Worthy, Z. Weiss, M. Grabowicz, N. Vega, B.R. Levin (2020) Mucoidy, a general mechanism for maintaining lytic phage in populations of bacteria FEMS Microbiology Ecology PDF

• Friberg, C., J. Haaber, M.Vestergaard, A.Fait, V. Perrot, B. Levin, H. Ingmer (2020)  Human antimicrobial peptide, LL-37, induces non-inheritable reduced susceptibility to vancomycin in Staphylococcus aureus Nature Research Scientific Reports 10:13121 PDF

• Bull, J.J., B.R. Levin, I.J. Molineaux. Promises and pitfalls of in vivo evolution to improve phage therapy (2019) Viruses 2019, 11, 1083; doi:10.3390/v11121083 PDF

• McCall, I.C., N. Shah, A. Govindan, F. Baquero, B.R. Levin. (2019) Antibiotic killing of diversely generated populations of non-replicating bacteria, Antimicrobial Agents and Chemotherapy, Antimicrobial Agents and Chemotherapy 63 :e02360-18. https://doi.org/10.1128/AAC.02360-18.PDF

• Gurney, J.G., M. Pleška, B.R. Levin. (2019) Why put up with immunity when there is resistance: an excursion into the population and evolutionary dynamics of restriction–modification and CRISPR-Cas. Ph. Trans. Royal Soc. B 374: 20180096. http://dx.doi.org/10.1098/rstb.2018.0096 PDF

• Dickey, J.G., and V. Perrot. (2019) Adjunct phage treatment enhances the effectiveness of low antibiotic concentration against Staphylococcus aureus biofilms in vitro. PLoS One 14(1) e0209390 PDF

• Balaban, N. Q., S. Helaine, K. Lewis, M. Ackermann, B. Aldridge, D. I. Andersson, M. P. Brynildsen, D. Bumann, A. Camilli, J. J. Collins, C. Dehio, S. Fortune, J. M. Ghigo, W. D. Hardt, A. Harms, M. Heinemann, D. T. Hung, U. Jenal, B. R. Levin, J. Michiels, G. Storz, M. W. Tan, T. Tenson, L. Van Melderen and A. Zinkernagel (2019). "Definitions and guidelines for research on antibiotic persistence." Nat Rev Microbiol. April 12, 2019 PDF

• Nicoloff, H., K. Hojort, B. R. Levin and D. A. Andersson, (2018) The high prevalence of antibiotic heteroresistance in pathogenic bacteria is mainly caused by gene amplification. Nature Microbiology Vol. 4 March 2019, 504-514 PDF Supplemental PDF

• Chaudhry WN, M. Pleska, N.N. Shah, H. Weiss, I.C. McCall, J.R. Meyer, A. Gupta, C.C. Guet, B.R. Levin BR. (2018) Leaky resistance and the conditions for the existence of lytic bacteriophage. PLoS Biol 16:e2005971. PDF

• Dewan KK, Skarlupka AL, Rivera I, Cuff LE, Gestal MC, Taylor-Mulneix DL, Wagner S, Ryman VE, Rodriguez C, Hamidou Soumana I, Levin BR, Harvill ET (2018) Development of macrolide resistance in Bordetella bronchiseptica is associated with the loss of virulence. J Antimicrob Chemother doi:10.1093/jac/dky264. PDF

• Pleška, M. D Refardt, B. Levin, M. Lang, C. Guet (2018) Phage-host population dynamics promotes prophage acquisition in bacteria with innate immunity. Nat Ecol Evol, 2018. 2(2): p. 359-366. PDF

• Weissman, J. R. Holmes, R. Barrangou, S. Moineau, W. Fagan, and B.R. Levin, Johnson, P., J (2018)  Immune loss as a driver of coexistence during host-phage coevolution. ISME, 2018: p. 1-13.   PDF                                                                                           

• Shao, X, B. R. Levin and I. Nemenman (2017) Single variant bottleneck in the early dynamics of bacteremia in neonatal rats questions the theory of independent action.  Physical Biology.  14: 045004 PDF

•  Wu, X., N.T.Jacobs, C.A. Bozio, P. Palm, S.M. Lattar, Lattar, C.R Hanke, D.M.  Watson, D. M., F, Sakai , Levin, B.,R. Klugman, and J.E. Vidal (2017). Competitive Dominance within Biofilm Consortia Regulate the Relative Distribution of Pneumococcal Nasopharyngeal Density. Applied and Environmental Microbiology. 83(16). pii: e00953-17. doi: 10.1128/AEM.00953-17.       

• Shao, X., A. Mugler, J. Kim, H.J. Jeong, B.R. Levin, I. Nemenman (2017) Growth of bacteria in 3-d Colonies.  PLoS Computational Biology 13(7) e1005679 PDF       

• Levin, B.R., F. Baquero, P. Ankomah, I.C.McCall (2017) Phagocytes, antibiotics and self-limiting bacterial infections. Trends in Microbiology. 25:878-892 PDF                                                                  

• Rook, G, F.  Bäckhed, B. Levin, M. McFall-Ngai, A. McLean (2017) Evolution, human-microbe interactions and life history plasticity.  The Lancet 390:  521-530 PDF

• Chaudhry, W.N, J. Concepcio-Acevedo, T. Park, S. Andleeb, J.J. Bull, B.R. Levin (2017) Synergy and order effects of antibiotics and phage in killing Pseudomonas aeruginosa biofilms.  PLoS ONE DOI:10.1371/journal.pone.0168615 PDF

• Levin, B.R., I.C. McCall, V. Perrot, H. Weiss, A. Ovespian, F. Baquero. (2017) A Numbers Game: Ribosome Densities, Bacterial Growth, and Antibiotic-Mediated Stasis and Death, mBIO 8 (1) e02253-16 PDF

• Concepcion-Acevedo, J., H. N. Weiss, W.N. Chadudhry, amd B.R.Levin 2015. Malthusian parameters as estimators of the fitness of microbes.  A cautionary tale about the low side of high throughput.  PLoS One Vol.10: Issue 6: e0126915 [PDF] 

• Levin, B.R., J. Concepcion Acevedo, K. Udekwu. (2014) Persistence: a copacetic and parsimonous hypothesis for non-inherited resistance to antibiotics.  Current Opinion in Microbiology 21: 18-21 [PDF]

• Levin, B.R., F. Baquero, P.J. Johnsen 2014. A model-guided analysis and perspective on the evolution and epidemiology of anitbiotic resistance and its future.  Current Opinion in Microbiology 19: 83 - 89 [PDF]

• Ankomah, P. B.R. Levin 2014.  Exploring the collaboration between antibiotics and the immune response in the treatment of acute, self-limiting infections. PNAS 111:8331-8338  [PDF]  

• Bull, J.J. C. S.Vegge, M. Schmerer, WN Chaudhry, BR Levin. 2014.  Phenotypic resistance and the dynamics of bacterial escape from phage control.  PLoS One April 2014 | Volume 9 | Issue 4 | e94690 [PDF]

• Jiang W, Maniv I, Arain F, Wang Y, Levin BR, et al. (2013) Dealing with the Evolutionary Downside of CRISPR Immunity: Bacteria and Beneficial Plasmids. PLoS Genet 9(9): e1003844. doi:10.1371/journal.pgen.100384 [PDF]

• Turrientes, MC Levin, BR, Martínez,JL, Ripoll, A, Baquero, MR Rodríguez-Domínguez,M, González-Alba, JM, Cantón,R,  Baquero, F. and Galán, JC, 2013,  Emergence of Normo-Mutable Variants from a Escherichia coli Mutator Clinical Strain During a Long-Term Serial Passages Experiment PLoS One: Volume 8 | Issue 9 | e72963 [PDF]

• Ankomah, P, P.T.Johnson and B. R. Levin (2013) The Pharmaco –, Population and Evolutionary Dynamics of Multi-Drug Therapy Experiments with S. aureus and E. coli and Computer Simulations 9(4) e1003300  [PDF]

• Levin, B.R., S. Moineau, M. Bushman, R. Barrangou (2013) The population and evolutionary dynamics of phage and bacteria with CRISPR-mediated immunity.  PLoS Genetics 9: 3 e1003312 [PDF]

• Johnson, P.J.T. and B.R. Levin (2013) Pharmacodynamics, population dynamics and the evolution of persistence in Staphyloccus aureus.  PLoS Genetics Vol 9, Issue 1, e1003123 [PDF]

• Kirby, A.E (2013) Synergistic action of gentamicin and bacteriophage in a continuous culture population of Staphyloccus aureus.  PLoS One Vol. 7, Issue 11, e51057 [PDF]                  

• Kirby, A.E., K. Garner and B.R. Levin (2012) The relative contributions of physical structure and cell density to the antibiotic susceptibility of bacteria in bioflims.  Antimicrobial Agents and Chemotherapy 56(6) 2867-2975 [PDF]

• Udekwu, K and B.R. Levin (2012)    Staphylococcus aureus in continuous culture: A tool for the rational design of antibiotic treatment PLoS one Vol. 7 Issue 7m  e3866 [PDF]

• Chien, Y-W, B.R. Levin and K. Klugman (2012) The anticipated severity of a "1918-like" influenza pandemic in contemporary populations:  the contribution of antibacterial interventions [PDF]

• Ankomah, P and B. R. Levin (2012) Two-drug antimicrobial chemotherapy: A mathematical model and experiments with Mycobacterium marinum.  Plos Pathogens 8: 1 e1002487 [PDF]

• Wei, Y. A, Kirby and B.R. Levin (2011) The population and evolutionary dynamics of Vibrio cholerae and its bacteriophage: conditions for maintining phage-limited communities Amer, Natur. 178:715-725.[PDF]

• Wei, Y, Z. Wang, J. Liu, I. Nemenman,   A.H. Singh, H. Weiss and B.R. Levin (2011) The population dynamics of bacteria in physically structured habitats and the adaptive virtue of random motility. PNAS 108:4047-4052 [PDF]

•  Levin, B.R. (2011) Population geneticists discover bacteria and their genetic/molecular epidemiology.  IN Population Genetics of Bacteria:  A Tribute to Thomas S. Whittam, S.T. Walk and P.C. Fang Editors.  ASM Press  [PDF]

• Haber, M. B.R. Levin and P. Kramarz (2010) Antibiotic control of antibiotic resistance in hospitals: A simulation study. BMC Infectious Diseases  10:254 [PDF]

• Levin, B.R. (2010) Nasty viruses, costly plasmids, population dynamics and the conditions for maintaining CRISPR-mediated adaptive immunity in bacteria.  PLoS Genetics 10:6 E1001171 [PDF]

• Wei, Y, P. Ocampo and B. R. Levin (2010) An Experimental study of the population and evolutionary dynamics of vibrio cholerae O1 and the Bacteriophage JSF4. Proc. Royal Soc. Lond. B On Line [PDF]

• Levin, B.R. and K. Udekwu (2010) The population dynamics of antibiotic treatment:  a mathematical model and hypotheses for time-Kill and continuous culture experiments. Antimicrobial Agents and Chemotherapy 54(8): 3414-3426 [PDF]

• Margolis, E. A. Yates, and B.R. Levin (2010) The ecology of nasal colonization of Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus: the role of competition and interactions with host's immune response.  BMC Microbiology 2010, 10:59 doi:10.1186/1471-2180-10-59 [PDF]

• Cornejo OE, McGee, L. and DE Rozen (2010).   Polymorphic competence peptides does not restrict recombination in Streptococcus pneumoniae.  Molecular Biology and Evolution 27(3): 694-702. [PDF] [Supplementary Online Materials]

• Johnsen, P.J and B.R. Levin (2010) Adjusting to alien genes.  Molecular Microbiology On Line [PDF]

Current research support (grants):

1. Theoretical and Experimental Studies of the Population and Evolutionary Dynamics of Bacteria and Bacteriophage. Levin (PI), 4/1/2020-3/31/2025  1R35GM136407-01

2. Heteroresistance Interdisciplinary Research Unit. D.S. Weiss (PI), Levin (CoPI),
   03/01/21-02/28/26 5U19AI158080