Research: Biomedical Science, Ecology & Evolutionary Biology
- Ph.D. Agricultural Sciences, Ghent University, 1993
- B.S./M.S. Bioengineering, Ghent University, 1989
My research is currently focused on the evolution and ecology of plasmids that transfer to and replicate in a broad range of bacteria. Plasmids are mobile genetic elements found in most bacteria. Because they readily transfer between different types of bacteria under natural conditions, they play an important role in rapid bacterial adaptation to changing environments. A good example is the current epidemic of multiple antibiotic resistance in human pathogens, which is largely due to the spread of multi-drug resistance plasmids. Although plasmid-mediated gene transfer is now recognized as a key mechanism in the alarming rise of antibiotic resistance, little is known about their host range, their ability to invade bacterial populations in the absence of selection, and their genetic diversity. We are addressing these questions using various Proteobacteria and plasmids as model systems.
Selection of publications in peer-reviewed journals (from over 100 total)
- Loftie-Eaton, W., K. Bashford, H. Quinn, K. Dong, J. Millstein, S. Hunter, M. Thomason, H. Merrikh, H., J.M. Ponciano, and E.M. Top. 2017. Compensatory mutations improve general permissiveness to antibiotic resistance plasmids. Nature Ecol. Evol. 1: 1354–1363.
- Stalder, T., L. M. Rogers, C. Renfrow, H. Yano, Z. Smith, and E.M. Top. 2017. Emerging patterns of plasmid-host coevolution that stabilize antibiotic resistance. Scientific Reports 7: 4853.
- Thomas, C.M., N. R. Thomson, A. M. Cerdeño-Tárraga, C. J. Brown, E.M. Top, and L. S. Frost. 2017. Annotation of Plasmid Genes. Plasmid 91:61-67.
- Ridenhour, B., G. Metzger, M. France, K. Gliniewicz, J. Millstein, L. Forney, E.M. Top. 2017.Persistence of antibiotic resistance plasmids in bacterial biofilms. Evol. Appl. 10:640-647.
- Stalder, T., and E.M. Top. 2016. Plasmid transfer in biofilms: A perspective on limitations and opportunities. NPJ Biofilms and Microbiomes. 16022: 1-5.
- Yano H., K. Wegrzyn, W. Loftie-Eaton, J. Johnson, G.E. Deckert, L.M. Rogers, I. Konieczny, and E.M. Top. 2016. Evolved plasmid-host interactions reduce plasmid interference cost. Mol. Microbiol. 101: 743-756.
- Loftie-Eaton, W. H. Yano, S. Burleigh, R.S. Simmons, J.M. Hughes, L.M. Rogers, S.S. Hunter, M.L. Settles, L.J. Forney, J.M. Ponciano, and E.M. Top. 2016. Evolutionary paths that expand plasmid host-range: implications for spread of antibiotic resistance. Mol. Biol. Evol. 33: 885–897.
- Li, X., Y. Wang, C. Brown, F. Yao, Y. Jiang, E.M. Top, and H. Li. 2016. Diversification of broad host range plasmids correlates with the presence of antibiotic resistance genes. FEMS Microbiol. Ecol. 92: fiv151.
- Li, X., E. M. Top, Y. Wang, C. J. Brown, Y. Jiang, and H. Li. 2015. The broad-host-range plasmid pSFA231 isolated from petroleum-contaminated sediment represents a new member of the PromA plasmid family. Frontiers in Microbiology 5: 777 (1-12).
- Loftie-Eaton, W., H. Suzuki, K. Bashford, H. Heuer, P. Stragier, P. De Vos, M.L. Settles, and E. M. Top 2015. Draft genome sequence of Pseudomonas sp. nov. H2. Genome Announcement 3: e00241-15.
- Loftie-Eaton, W., A. Tucker, A. Norton, and E. M. Top. 2014. Flow cytometry and Real-Time qPCR as tools for assessing plasmid persistence. Appl Environ Microbiol. 80: 5439-5446 (PMCID: PMC4136099).
- Hunter, S., H. Yano, W. Loftie-Eaton, J. Hughes, L. De Gelder, P. Stragier, P. De Vos, M. Settles, and E. M. Top. 2014. Draft genome sequence of Pseudomonas moraviensis R28. Genome Announcement 2: e00035-14. (PMCID: PMC3931354).
- Brown, C. J., D. Sen, H. Yano, M. L. Bauer, L. M. Rogers, G. A. Van der Auwera, and E. M. Top. 2013. Diverse broad-host-range plasmids from freshwater carry few accessory genes. Appl. Environ. Microbiol. 79: 7684-7695. (PMCID: PMC3837812)
- Yano, H., L.M. Rogers, M.G. Knox, H. Heuer, K. Smalla, C.J. Brown, and E. M. Top. 2013. Host range diversification within the IncP-1 plasmid group. Microbiology 159: 2303-2315. (PMCID: PMC3836486)
- Oliveira, C.S., A. Moura, I. Henriques, C.J. Brown, L.M. Rogers, E. M. Top, and A. Correia. 2013. Comparative genomics of IncP-1ε plasmids from water environments reveals diverse and unique accessory genetic elements. Plasmid 70: 412-149.
- Król, J. E., A. J. Wojtowicz, L. M. Rogers, H. Heuer, K. Smalla, S. M. Krone, and E. M. Top 2013. Invasion of E. coli biofilms by multidrug resistance plasmids. Plasmid 70: 110–119. (PMCID: PMC3687034)
- Sen, D., C.J. Brown, E. M. Top and J. Sullivan. 2013. Inferring the evolutionary history of IncP-1 plasmids despite incongruence among backbone gene trees. Mol. Biol. Evol. 30: 154-166. (PMCID: PMC3525142)
- Yano H, Genka H, Ohtsubo Y, Nagata Y, Top E.M., Tsuda M. 2013. Cointegrate-resolution of toluene-catabolic transposon Tn4651: Determination of crossover site and the segment required for full resolution activity. Plasmid 69: 24–35.
- Hughes, J.M., B.K. Lohman, G.E. Deckert, E.P. Nichols, M. Settles, Z. Abdo, and E. M. Top. 2012. The role of clonal interference in the evolutionary dynamics of plasmid-host adaptation. mBio 3(4): e00077-12.
- Stolze, Y., F. Eikmeyer, D. Wibberg, G. Brandis, C. Karsten, I. Krahn, S. Schneiker-Bekel, P. Viehöver, A. Barsch, M. Keck, E. Top, K. Niehaus, A.Pühler, and A. Schlüter. 2012. IncP-1beta plasmids of Comamonas sp. and Delftia sp. strains isolated from a wastewater treatment plant mediate resistance to and decolorization of the triphenylmethane dye crystal violet.Microbiology.158: 2060-2072.
- Van Meervenne, E., E. Van Coillie, F. Devlieghere, L. Herman, L.S.P. De Gelder, E. M. Top, and N. Boon. Strain specific transfer of antibiotic resistance from an environmental plasmid to foodborne pathogens. J. Biomed. Biotechnol. 2012: ID 834598.
- Yano, H., G. E. Deckert, L. M. Rogers, and E. M. Top. 2012. The role of long and short replication initiation protein in the fate of IncP-1 plasmids. J. Bacteriol. 194: 1533–1543.
- Eikmeyer, F.G., R. Szczepanowski, D.Wibberg, A. Hadiati, S. Schneiker-Bekel, L. M. Rogers, C.J. Brown, E. M. Top, A. Pühler, A. Schlüter. 2012. The complete genome sequences of four new IncN plasmids from wastewater treatment plant effluent provide new insights into IncN plasmid diversity and evolution. Plasmid 68: 13-24
- Heuer, H., C.T.T. Binh, S. Jechalke, C. Kopmann, U. Zimmerling, E. Krögerrecklenfort, T. Ledger, B. Gonzalez, E. M. Top, K. Smalla. 2012. IncP-1ε plasmids are important vectors of antibiotic resistance genes in agricultural systems: diversification driven by class 1 integron gene cassettes. Frontiers in Microbiology 3: Article 2. http://www.ncbi.nlm.nih.gov/pubmed/22279444
- Król, J.E., J.T. Penrod, H. McCaslin, L.M. Rogers, H. Yano, W. Dejonghe, C.J. Brown, R.E. Parales, S. Wuertz, E. M. Top. 2012. Genomic and functional analysis of the IncP-1β plasmids pNB8c and pWDL7::rfp explains their role in 3-chloroaniline catabolism. Appl. Environ. Microbiol. 78: 828-838. http://www.ncbi.nlm.nih.gov/pubmed/22101050
- Zhong, X., J. Droesch, R. Fox, E. M. Top, and S M. Krone. 2012. On the meaning and estimation of plasmid transfer rates for surface-associated and well-mixed bacterial populations. J. Theor. Biol. 294: 144–152. http://www.ncbi.nlm.nih.gov/pubmed/22085738
Dr. Top's lab is a member of Biology, Institute for Bioinformatics and Evolutionary Studies (IBEST) and the Bioinformatics & Computational Biology (BCB) Graduate Programs.
- Plasmid-Host Interaction and Evolution of Plasmid Host-Range
Since rapid plasmid-mediated spread of multi-drug resistance to human pathogens is threatening our ability to fight against infectious diseases, we urgently need novel therapies aimed at limiting the spread of new resistance genes. However, little is known about what determines the range of bacteria in which a plasmid can be maintained. Moreover we do not know if and how, and at what tempo that host range can expand, contract or shift over time. Since bacteria evolve very rapidly their drug resistance plasmids can also quickly adapt to novel hosts by reducing their cost and becoming more stable even in the absence of the drugs. The new project aims at discerning patterns of plasmid host range evolution in bacteria through (i) experimental evolution studies followed by (ii) molecular and biochemical analysis of evolved plasmids, and (iii) mathematical and statistical modeling of the evolutionary processes. For example, we found that the stability of a drug resistance plasmid in a novel host can rapidly improve in bacterial populations through mutations in the plasmid alone, the host chromosome alone, or both, and that a single mutation in a plasmid can have a dramatic effect on its host range. This project is in collaboration with Dr. Zaid Abdo and funded by the National Institute of Allergies and Infectious Disease (NIAID) of the National Institutes of Health (http://www.niaid.nih.gov).
- Evolution of plasmid persistence in biofilms
A second project was recently funded by the Department of Defense, through a Military Infectious Diseases Basic Research Award. Infections of wounds incurred in combat greatly threaten the lives of those who survive the first hours after injury. Hospital acquired infections of combat wounds in military treatment facilities and other nosocomial infections present a major health crisis today because they are commonly caused by multi-drug resistant (MDR) bacteria. These bacteria also form biofilms in the wounds, which renders them even more resistant. Unfortunately, biofilms are also considered ‘hot-spots’ for plasmid transfer, and plasmids can in turn promote biofilm formation. The goal of the proposed research is to gain insight into the evolutionary mechanisms by which drug resistance plasmids can improve their persistence in biofilms formed by bacteria known to cause wound infections. The central hypothesis is that the evolutionary pathways through which plasmid persistence improves are different and more varied in biofilms than in well-mixed liquids due to the spatially structured environment of biofilms that is absent in liquids
- The Genetic Diversity of Broad-host-Range Plasmids in Bacteria
A third project aims at enhancing our understanding of the diversity and evolutionary history of the extant pool of BHR plasmids. This is done by comparative genomic and phylogenetic analysis of the complete genome sequences of natural plasmids. This project was funded by the National Science Foundation, and the DNA sequencing service has been provided by Department of Energy Joint Genome Institute. Co-investigators are Professors Celeste Brown, Jack Sullivan, and Larry Forney. Future research will focus on the evolutionary history of plasmids: What are the current plasmids' long-term host reservoirs, and do plasmids evolve mostly by vertical descent or through lateral exchange of core genes between plasmids?
- 1989 Prize of the Alumni Society of Agricultural Engineers for academic achievement and community service (in Dutch: ‘de meest verdienstelijke student’; out of ca. 100 seniors, Ghent University, Belgium)