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 ammendent 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 have sex with, but bacteria are far better for research'
Our research includes mathematical and computer simulation modeling and in vitro and laboratory animal experiments on the population and evolutionary biology of bacteria and their viruses and accessory genetic elements. In addition to investigations addressing precious academic ecological and evolutionary questions, we also do studies applying population dynamic and evolutionary theory and experiments to health-related problems. Among the latter are investigations of the epidemiology of pathogenic bacteria, antimicrobial chemotherapy and the evolution of resistance, the pharmacodynamics and pharamacokinetics of antibiotics and the within-host population and evolutionary dynamics of bacterial infections and their treatment with antibiotics.
The following is a list the projects on which we are currently (November 2017) working on or recently completed and the names of the primary investigator(s) involved in these studies. For more information about these projects, write to the first named investigator listed or Bruce
A theoretical and experimental study of the population and evolutionary dynamics of bacteria and phage in physically structured habitats. With Waqas Chaudhry, Nilang Shah, Esther Lee, and Howie Weiss (Georgia Institute of Technology)
The pharmaco- and population dynamics of sub-MIC antibiotic treatment of Staphylococcus. aureus - With Catherine Friberg, Klas Udekwu, Jeniffer Concepcion-Acevedo, Jessica Coates, Daniel Cox, Hanne Ingmer
The combined antibiotic and bacteriophage in the treatment of biofilm populations of Pseudomonas aeruginosa and Staphylococcus aureus. With Waquas Chaudhry, Veronique Perrot and James Dickey
The collaboration of antibiotics and the immune defenses in the treatment of bacterial infections. With Fernando Baquero (Ramon Cajhal Hospital, Madrid), Ingrid McCall and Monica Cartelle Gestal and Eric Harvill (at the University of Georgia)
The population and evolutionary dynamics lysogeny: Why be Temperate. With Waqas Chaudhry, Maros Pleska (The Rockefeller University) and Nicole Vega (Emory)
Antibiotic and phage sensitivity of non-growing populations of Staphylococcus aureus, Pseudomonas aeruginosa and E. coli. With Waqas Chaudhry, Nilang Shah, Adithi Govindan, Ingrid McCall and Fernando Baquero (Ramon Cajhal Hospital, Madrid),
Why put up with immunity, if you have resistance: An excursion into the population and evolutionary dynamics of restriction modification and CRISPR-Cas. With James Gurney (Georgia Institute of Technology) and Maros Pleska (The Rockefeller University).
Theoretical and experimental studies of the mechanisms responsible for maintaining stable communities of bacteria and bacteriophage. Experiments with E. coli, S. aureus, Seretia marcesense and Pseudomonas aeruginosa and their phage. With Waqas Chaudhry, Esther Lee, Brandon Berryhill, Nicole Vega (Emory) and Howie Weiss (Georgia Institute of Technology)
A study of the diversity of E. coli and their bacteriophage and the frequency and nature of antibiotic resistance in E. coli from sewage and other natural sources. With Melony Ivey and Ingrid McCall
The mechanisms of action, pharmaco- and population dynamics of hetero- antibiotic resistance in bacteria. With Hervé Nicoloff, Karin Hjort, and Dan I. Andersson (University of Uppsala, Sweden).
Ribosome numbers and the mechanisms of action of ribosome targeting bacteriostatic antibiotics in E. coli With Fernando Baquero (Ramon Cajhal Hospital, Madrid), Ingrid McCall and Christine Dunham (Emory)
Relatively recent publications from our Lab: For an almost complete list of our articles, click on "Publications"
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 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 heterogeneity in antibiotic resistance (heteroresistance) in pathogenic bacteria is mainly caused by gene amplification Nature Microbiology Vol. 4 March 2019, 504-514 PDF PDFSupplemental
Chaudhry WN, Pleska M, Shah NN, Weiss H, McCall IC, Meyer JR, Gupta A, Guet CC, 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
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]
Levin, B.R. and O.E. Cornejo (2009) The population and evolutionary dynamics of homologous gene recombination in bacteria. PLoS Genetics 5 (8) e1000601 [PDF]
Johnsen, P.J, D. Dubnau, and B. R. Levin (2009) Episodic selection and the maintenance of competence and natural transformation in Bacillus subtilis GENETICS 181: 1521-1533 [PDF]
Udekwu, K, N. Parrish, P. Ankomah, , F. Baquero and BR Levin (2009) Functional relationship between cell density and the efficacy of antibiotics. Journal of Antimicrobial Chemotherapy 63:745-767 [PDF]
Margolis, E. (2009) Hydrogen peroxide mediated interference competition by Streptococcus pneumoniae has no significant effect on Staphylococcal nasal colonization of neonatal rats J. Bact. 191: 571-575 [PDF]***
Cornejo, O.E., D. Rozen, R.M. May and B.R. Levin (2009) Oscillations in continuous culture populations ofStreptococcus pneumoniae: Population dynamics and the evolution of clonal suicide (Proceeding Royal Society B, 276: 999-1008 [PDF] [Supplemental On Line Material]***
Handel, A, E. Margolis and B.R. Levin (2008) Exploring the role of the immune response in preventing antibiotic resistance Journal of Theoretical Biology 256:666-662 [PDF]
Margolis, E. and B. R. Levin (2008) The evolution of bacteria-host interactions: virulence and the immune over-response. IN “Introduction to the Evolutionary Biology of Bacterial and Fungal Pathogens ” J-A. Gutteriez and F.M. Baquero Editors (ASM Press) [PDF] Also published in "Microbial Evoiution and Co-Adaptation: A Tribute to the Life and Scientific Legacies of Joshua Lederberg (2009) P. 137:157 ( http://www.nap.edu/catalog/12586.html) For the whole Pathogen Evolution Chapter[PDF]
Lemonnier , M, B.R. Levin, T. Romeo, K, Garner, M-R. Baquero, J. Mercante, E. Lemichez, F. Baquero, and J. Blázquez (2008) Evolution of contact-dependent inhibition in non-growing populations of E. coli. Proc. Roy. Society B Proc. Royal Soc. B. 275:3-10[PDF] [Supplemental On Line Material]***
Margolis, E. and B.R. Levin 2007 Within–Host Evolution for the Invasiveness of Commensal Bacteria: an experimental study of bacteremias resulting from Haemophilus influenzae nasal carriage, Journal of Infectious Disease 175: 1069-1075.[PDF]
Rozen, D. E. L.E. McGee, B.R. Levin and K. P. Klugman (2007) .The fitness costs of fluoroquinolone resistance in Streptococcus pneumoniae. Antimicrobial Agents and Chemotherapy, 51:412-416.[PDF]
Meltz-Steinberg, K. and B.R. Levin (2007) Grazing protozoa and the evolution of the Escherichia coli O157:H7 Shigatoxin-encoding prophage. Proceedings of the Royal Society of London B Series (Biology) 274: 1921 - 1929.[PDF]
Lipsitch, M., T. Cohen, M. Murray, B.R. Levin (2007) Antiviral resistance and the control of pandemic influenza. PLoS Med 41: e15.[PDF]
Current research support (grants):
Theoretical and experimental studies of the population and evolutionary dynamics of antibiotic treatment. National Institutes of Health 9R01GM091875-17