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Indiana University Bloomington

Department of Biology

Faculty & Research

Faculty Profile

Dean Rowe-Magnus

Photo of Dean Rowe-Magnus
Research Images
Research photo by Dean Rowe-Magnus

Figure 1. Schematic representation of a circularized cassette (A) and model for cassette exchange (B). A: The key features of attC sites (triangles) are the inverse core-site (ICS) and core-site (CS) consensus sequences (red arrows) and the imperfect palindrome variable region (red deshed arrows).  The black triangle in the attC symbol represents the recombination point in the CS sequences (black arrow). The representative attC Sites of antibiotic resistance (AbR) gene cassettes are shown below. B: Outline of the process by which circular AbR gene cassettes are repeatedly inserted at the attl site in a class1 integron downstream of the strong promoter Pc.  The different attC sites are represented by different fill patterns for the triangles.  intl1, integrase encoding gene; Int, integrase Int1; double triangles attC sites, I; ICS; C, CS.

Research photo by Dean Rowe-Magnus

Figure 2. Structural comparison of a "classical" resistant integron and theV. cholerae 569B super-integron. Top: Schematic representation of a MRI; the various resistance genes (green boxes) are associated with different attC sites. Antibiotic resistance cassettes confer resistance to the following compounds:dvrVI, trimethoprim; cmlA2, chloramphenicol;,aadA1a, aminoglycosides oxa9, b-lactams. The qacEΔ and sulgenes, which provide resistance to quaternary ammonium compounds and sulfonamides, repsectively, are not gene cassettes. Bottom: The ORFs are separated by highly homologous sequences, the VCRs; gray boxes are ORFs that are not part of the SI structure. Note: all the aaC sites are in the same orientation, while some of the cassette ORFs are in the opposite orientation.

Research photo by Dean Rowe-Magnus

Figure 3.

Research photo by Dean Rowe-Magnus

Figure 4.

Associate Professor of Biology
Contact Information
By telephone: 812-855-8514/6-0723(lab)
By fax: 812-856-6705
JH 451(lab)
Program
Microbiology
Research Areas
  • Evolution
  • Genomics and Bioinformatics
  • Microbial Interactions and Pathogenesis
Education

B.Sc., University of Ottawa, 1991
M.Sc., University of Toronto, 1994
Ph.D., University of British Columbia, 1998
Postdoctoral Training, Institut Pasteur, Paris, France, 2002 

Awards

2005 Premier’s Research Excellence Award
2001 Fondation de la Recherche Medicale Post-doctoral Fellowship
2000 European Molecular Biology Organization (EMBO) Postdoctoral Fellowship 
1999 EMBO Postdoctoral Fellowship
1998 Manlio Cantarini Postdoctoral Fellowship for the Institut Pasteur 

Research Description

Evolution: The role of Integrons and Super-integrons

HGT among the prokaryotes is a perpetual phenomenon that has a profound impact on bacterial evolution. The most striking example of this is the emergence and spread of antibiotic resistance among human bacterial pathogens over the past seven decades. It is now clear that acquisition of a gene from an exogenous source that confers resistance is the most common solution adopted by bacteria to escape antimicrobial activity, rather than mutation in a resident gene. Integrons are specialized genetic systems that capture functional genes, known as gene cassettes, by site-specific recombination (fig. 1) and they are the primary mechanism for antibiotic-resistance gene capture and dissemination among Gram-negative bacteria. More than 100 different antibiotic resistance genes, covering most classes of antimicrobials presently in use, are structured as gene cassettes in integrons. The stockpiling of these cassettes in integrons has contributed substantially to the current dilemma in the treatment of infectious disease, as integrons containing up to 8 resistance cassettes have been found in multiple-resistant clinical isolates. The association of integrons with mobile DNA elements such as transposons and plasmids facilitates their transit across phylogenetic boundaries and augments the impact of integrons on bacterial evolution. 

Our finding of massive ancestral versions called super-integrons (SI) in the genomes of diverse bacterial species (fig. 2) has expanded the role of integrons in genome evolution. Containing more than 200 cassettes, the SIs of the Vibrionacea are the largest identified to date. Although the vast majority of SI gene cassettes are of unknown function, some of the genes they harbor are related to virulence and antibiotic resistance determinants characterized in clinical isolates. Furthermore, we have shown that several gene cassettes code for additional adaptive functions such as toxins, restriction enzymes and metabolic enzymes. This suggests that the activity of integrons permits bacteria to rapidly adapt to environmental changes by scavenging foreign genes that may ultimately endow the bacterium with an adaptive advantage. The epidemiology and pathogenesis of infections caused by Vibrio species differ significantly. Our lab is characterizing the SIs of the Vibrionaceae using a combination of sequencing, in vitro biochemical analysis, in vivo genetic manipulation, and DNA array and expression analysis. These studies will allow us to begin addressing questions about the role of SIs in the evolution of the Vibrionaceae into potent human and successful environmental organisms. A comparison of the SIs from these species should also reveal both common and unique cassettes that may yield clues about their common or unique function in the adaptation and evolution of this bacterial family.

Ecology

Vibrio vulnificus (fig. 3) is a marine bacterium that is pathogenic to both humans and animals. The bacterium is highly invasive, causing primary septicimia and wound infections worldwide. The fatality rate of susceptible patients with primary septicimia can reach 75%, and death often occurs within hours of hospital admission. It alone is responsible for 95% of all seafood-related deaths in the United States and it carries the highest death rate of any food-borne disease agent. V. vulnificus forms biofilms on the surface of and colonizes plankton, algae, fish, eels and humans. It also exhibits a rugose phenotype and these variants form better biofilms and are more resistant to environmental stresses than non-rugose variants, suggesting that this phenotype contributes to the persistence of the bacteria in aquatic ecosystems. Greater understanding of biofilm formation and the rugosity could provide insight into approaches to decrease the Vibrio load in filter feeders and on biotic surfaces, and control the occurrence of invasive disease. It has recently come to light that the second messenger c-di-GMP (fig. 4) regulates a variety of cellular processes associated with the transition between planktonic and sessile lifestyles in many bacteria. Diguanylate cyclases synthesize the signaling molecule and phosphodiesterases degrade it and the activity of these enzymes is regulated by specific environmental signals. Receptor proteins bind c-di-GMP and affect a cellular response. In general, high intracellular concentrations of c-di-GMP promote biofilm formation and rugosity while repressing motility and virulence gene expression. We are characterizing how c-di-GMP, as well as other factors, regulates survival phenotypes in V. vulnificus. The characterization of biofilm formation and the rugose phenotype in V. vulnificus should advance our understanding of how the bacteria persists in the environment and how it switches from a free-swimming organism to colonizing oysters to invading human tissue.

Select Publications
Neiman J, Guo Y, Rowe-Magnus DA. 2011. Chitin-induced carbotype conversion in Vibrio vulnificus. Infect Immun. 79(8):3195-203.
Guo Y, Rowe-Magnus DA. 2011. Overlapping and unique contributions of two conserved polysaccharide loci in governing distinct survival phenotypes in Vibrio vulnificus. Environ Microbiol. 13(11):2888-990.
Nakhamchik A, Wilde C, Chong H, Rowe-Magnus DA. 2010. Evidence for the horizontal transfer of an unusual capsular polysaccharide biosynthesis locus in marine bacteria. Infect Immun. 78(12):5214-22.
Guo Y, Rowe-Magnus DA. 2010. Identification of a c-di-GMP-regulated polysaccharide locus governing stress resistance and biofilm and rugose colony formation in Vibrio vulnificus. Infect Immun. 78(3):1390-402.
Rowe-Magnus DA. 2009. Integrase-directed recovery of functional genes from genomic libraries. Nucleic Acids Res. 37(17):e118.
Vinogradov E, Wilde C, Anderson EM, Nakhamchik A, Lam JS, Rowe-Magnus DA. 2009. Structure of the lipopolysaccharide core of Vibrio vulnificus type strain 27562. Carbohydr Res. 344(4):484-90.
Nakhamchik A, Wilde C, Rowe-Magnus DA. 2008. Cyclic-di-GMP regulates extracellular polysaccharide production, biofilm formation, and rugose colony development by Vibrio vulnificus. Appl Environ Microbiol. 74(13):4199-209.
Nakhamchik A, Wilde C, Rowe-Magnus DA. 2007. Identification of a Wzy polymerase required for group IV capsular polysaccharide and lipopolysaccharide biosynthesis in Vibrio vulnificus. Infect Immun. 75(12):5550-8.
Szekeres S, Dauti M, Wilde C, Mazel D, Rowe-Magnus DA. 2007. Chromosomal toxin-antitoxin loci can diminish large-scale genome reductions in the absence of selection. Mol Microbiol. 63(6):1588-605.
Demarre G, Guerout AM, Matsumoto-Mashimo C, Rowe-Magnus DA, Marliere P, Mazel D. 2005. A new family of mobilizable suicide plasmids based on broad host range R388 plasmid (IncW) and RP4 plasmid (IncPalpha) conjugative machineries and their cognate Escherichia coli host strains. Res Microbiol. 156(2):245-55.
Rowe-Magnus DA, Guerout AM, Biskri L, Bouige P, Mazel D. 2003. Comparative analysis of superintegrons: engineering extensive genetic diversity in the Vibrionaceae. Genome Res. 13(3):428-42.
Rowe-Magnus DA, Mazel D. 2002. The role of integrons in antibiotic resistance gene capture. Int J Med Microbiol. 292(2):115-25.
Rowe-Magnus DA, Guerout AM, Mazel D. 2002. Bacterial resistance evolution by recruitment of super-integron gene cassettes. Mol Microbiol. 43(6):1657-69.
Rowe-Magnus DA, Guerout AM, Ploncard P, Dychinco B, Davies J, Mazel D. 2001. The evolutionary history of chromosomal super-integrons provides an ancestry for multiresistant integrons. Proc Natl Acad Sci U S A. 98(2):652-7.
Rowe-Magnus DA, Mazel D. 2001. Integrons: natural tools for bacterial genome evolution. Curr Opin Microbiol. 4(5):565-9.

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