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 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 address purely academic ecological and evolutionary questions, the primary focus of out research is the application of the theory and methodology of population and evolutionary biology to health related issues. The following is a list the projects on which we are currently (October 2019) working or recently completed 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   Bruce  or click on the highlighted names.

• The collaboration of antibiotics and the immune defenses in the treatment of bacterial infections.  With Fernando Baquero (Ramon Cajhal Hospital, Madrid), David Weiss, and Ingrid McCall

• A theoretical and experimental studies of the combined action of antibiotics and bacteriophage for the treatment of Staphylococcus aureus infections. With Brandon Berryhill, Adithi Govindan, Ingrid McCall, and David Weiss.

• The population and evolutionary dynamics lysogeny: Why be Temperate revisited.  With Waqas Chaudhry, Esther Lee, Adithi Govindan, Nicole Vega and Rodrigo Garcia

• Theoretical and experimental studies of the mechanisms responsible for maintaining stable communities of bacteria and bacteriophage. Experiments with E. coli, S. aureus, and Pseudomonas aeruginosa and their phage. With Waqas Chaudhry, Esther Lee, Brandon Berryhill, Marcin Grabowicz, Nicole Vega (Emory) and Howie Weiss (Penn State University)

• 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 in collaboration with Sarah Satola, Alexander Page, and Michelle Hargita.

• The mechanisms of action of ribosome targeting bactericidal and bacteriostatic antibiotics  With Fernando Baquero (Ramon Cajhal Hospital, Madrid), Ingrid McCall, David Weiss and Christine Dunham (Emory)

• A theoretical and experimental study of conditions for the evolution of antagonistic interactions between competing populations of Pseudomonas aeruginosa and Staphylococcus aureus. With Ross Greenberg with Marvin Whiteley, Joanna Goldberg and Nicole Vega

• The population and evolutionary dynamics of lytic and temperate phage and conjugative plasmids and bacteria with CRISPR-Cas - mediated immunity. With Brandon Berryhill, Waqas Chaudhry and Ingrid McCall in collaboration with Edze Westra (University of Exeter) and Luciano Marraffini (The Rockefeller University).

• The contribution of the human antimicrobial peptide LL37 to antibiotic treatment of Staphylococcus aureus infections. In collaboration with C. Friberg,J.Haaber, M. Vedtergaard A. Fait, and Hanna Ingmer (University of Copenhagen) and V. Perrot (Emory)

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

• Berryhill, B. I.C. McCall, D. Huseby, D.Hughes, and B.R. Levin Joint antibiotic and phage therapy: addressing the limitations of a seemingly ideal phage for treating Staphylococcus aureus infections (Under Review) 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. In Press Nature Reviews Microbiology 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 In Press FEMS Microbiology Ecology PDF

• Chaudhry, W. Pleska M, Vega, N, A, Govindan, R.Garcia, E. Lee, I. McCall, B. R. Levin. The population and evolutionary dynamics of bacteriophage: Why be temperate revisited (Under Revision)

• 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 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, 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]

• 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