David Dyer, PhD

Professor 

Ph.D.: 1983, Kansas State University

Pre-OUHSC: University of North Carolina at Chapel Hill; The State University of New York at Buffalo

Research Interests: Microbial genomics, bacterial iron transport, bacterial regulatory networks, microbial pathogenesis

Teaching: Molecular Microbiology, Microbial Pathogenesis, Medical Microbiology, Dental Microbiology

Email: David-Dyer@ouhsc.edu                                                                     Dr. Dyer's CV


 

Research Emphasis

Microbial genomics

One of our main interests is in microbial genomics. We have participated in several microbial genome sequencing projects, including Neisseria gonorrhoeae (the gonococcus), Aggregatibacter (formerly Actinobacillus) actinomycetemcomitansActinobacillus pleuropneumoniaeEdwardsiella ictaluri, Flavobacterium columnare, non-typeable Haemophilus influenzae and Histophilus somni (formerly Haemophilus somnus). We have recently finished the genome sequence of a Bacillus thuringiensis isolate, and have been sequencing the genomes of several Escherichia coli strains responsible for causing neonatal sepsis, in collaboration with Dr. Susana Chavez-Bueno of the Department of Pediatrics.  In an ongoing collaboration with Dr. James Chodosh, we are sequencing and analyzing the genomes of multiple isolates of Type D human adenoviruses, many of which are associated with epidemic keratoconjunctivitis, an ocular infection.

Regulation of gonococcal gene expression in response to iron availability

A second related interest is microbial pathogenesis.  Our laboratory has for some time been interested in the ability of pathogenic bacteria to obtain iron during growth in the human host. Current studies focus on N. gonorrhoeae.  The gonococcus can colonize almost any mucosal surface in the human body, although typically is seen infecting urogenital mucosae. Our current studies focus on the role of iron as an environmental signal controlling global gene expression responses.  Microarray analyses have demonstrated that iron availability directly or indirectly controls expression of ~20% of the gonococcal genome.  Direct control of gene expression in response to iron is in part due to the action of the Fur (ferric uptake regulation) protein, as in many other bacteria.  However, our data suggest that at least 11 other regulatory proteins and at least one sRNA (nrrF) also participate in controlling the gonococcal iron response.  We have identified all of the Fur binding sites in the gonococcal genome, and are currently examining the affinity of Fur for these DNA binding sites, to correlate this with gene expression patterns.  Examining the role of other regulatory factors in the gonococcal iron response continues.

Evolution of the regulation of gene expression in the Bacillus cereus sensu lato group.

The genus Bacillus is a heterogeneous group of Gram-positive heterotrophic aerobic or facultative anaerobic bacilli that form environmentally resistant, metabolically inert spores.  Within this large genus, the B. cereus sensu lato group consists of seven species [B. anthracis (Ba), B. cereus (Bc), B. mycoides, B. pseudomycoides, B. thuringiensis (Bt), B. weihenstephanensis (Bw) and B. cytotoxicus], based on classical microbial taxonomy. Recent molecular phylogenies and comparative genome sequence analysis indicate that these organisms should more accurately be viewed as a single species despite their phenotypic diversity. Thus, these organisms have arisen from a common ancestor to display impressive phenotypic diversity while occupying a close phylogenetic space.  Horizontal gene transfer (HGT), mobile genetic elements, and the routine processes of insertion/deletion (indel) formation have typically been invoked to explain the diversity in these organisms.  Clearly, mobile elements such as the virulence plasmids pXO1 and pXO2 in the Ba lineage, and the Cry toxin plasmids in various Bt strains, are essential for the phenotypes of these organisms.  On the other hand, it is unclear how much of the phenotypic diversity in these organisms can be explained by these mechanisms.  As a whole, Bc sensu lato organisms have an extremely high degree of chromosomal synteny, and whole genome comparisons between these organisms reveal a highly similar gene content. Other observations suggest that the most evolutionarily flexible portions of the bacterial genome are regulatory sequences and transcriptional networks. Thus, we hypothesize that many of the phenotypic characteristics that vary between these organisms are likely the result of divergence in the regulatory control of the shared gene content of these organisms.  We have recently shown that this is likely the case by an in silico analysis of the divergence of the SigB regulons of these organisms. Surprisingly, changes in promoter sequence between members of the Bc sensu lato group that ‘re-purpose’ conserved genes into/out of the SigB regulon appear to be more common than evidence of HGT or other mechanisms for remodeling the structure of this regulon. Four different lineages of the SigB regulon appear to have arisen during this process (see Fig. 1).  One lineage appears to carry the core SigB regulon that arose after the emergence of these organisms from a B. cytotoxicus-like ancestor. This lineage appears to have given rise to three additional clades that each appropriated different genes from a common gene pool into the SigB regulon, suggesting different strategies for the support of pathogenesis by the SigB-mediated generalized stress response.  Current studies will continue this approach to examine the divergence of other important elements in the B. cereus sensu lato regulome, including the plcR, ccpA and fur regulators.  Additional wet-bench experiments will test the hypotheses stemming from these in silico studies.


 
Figure 1: Proposed pathway for the divergence of the SigB regulon within the Bc sensu lato group.


Current Laboratory Personnel:

Jennie Allen, Bioinformatics Education Specialist

Michael Day, Research Assistant

Lydgia Jackson, Ph.D., Research Assistant Professor

Edgar Scott, Bioinformatics Education Specialist


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Selected Publications:

Schmidt, T.R., Scott II, E.J., and D.W. Dyer. Whole-genome phylogenies of the Family Bacillaceae and expansion of the sigma factor gene family in the Bacillus cereus species-group.  BMC Genomics 12: 430 (24 August 2011).

Liu, E.B., L. Ferreyra, S.L. Fischer, J.V. Pavan, S.V. Nates, N.R. Hudson, D. Tirado, D.W. Dyer, J. Chodosh, D. Seto and M.S. Jones.  Genetic Analysis of a Novel Human Adenovirus with a Serologically Unique Hexon and a Recombinant Fiber Gene. PLoS ONE 6 (9): e24491 (2011).

Siddaramappa, S., J. F. Challacombe, A. J. Duncan, A. F. Gillaspy, M. Carson, J. Gipson, M. Gipson, J. Orvis, J. Zaitshik, G. Barnes, D. Bruce, O. Chertkov, J. C. Detter, C. S. Han, R. Tapia, D. W. Dyer, and T. J. Inzana. Genome Sequence of Histophilus somni Strain 2336 from Bovine Pneumonia and Comparison to Commensal Strain 129Pt Reveal Extensive Horizontal Gene Transfer and Evolution of Pathogenesis.  BMC Genomics 12: 570 (2011).

Mullins, M.A., K.B. Register, D.O. Bayles, D.W. Dyer, J.S. Kuehn and G.J. Phillips. Genome sequence of Haemophilus parasuis strain 29755. Stds. Genom. Sci. 5 (1): 61-68 (2011).

Liu, E., D.A. Wadford, J. Seto, M. Vu, N.R. Hudson, L. Thrasher, S. Torres, D.W. Dyer, J. Chodosh, D. Seto and M S. Jones.  Computational and serologic analysis of novel and known viruses in species human adenovirus D in which serology and genomics do not correlate.  PLOS One 7(3): 33212 (2012).

Mercante, A.D., L. Jackson, P.J.T. Johnson, V.A. Stringer, D.W. Dyer, and W.M. Shafer.  MpeR regulates the mtr antimicrobial efflux locus in Neisseria gonorrhoeae and modulates antimicrobial resistance through an iron-responsive mechanism. Antimicrob. Ag. Chemother. Antimicrob. Ag. Chemother. 56 (3): 1491-1501 (2012).

Williams, M., A. Gillaspy, D.W. Dyer, R. Thune, G. Waldbieser, J.R. Gipson, J. Zaitshik, M. Banes and M. Lawrence.  Genome Announcement: Genome Sequence of Edwardsiella ictaluri 93-146, a Strain Associated with a Natural Channel Catfish Outbreak of Enteric Septicemia of Catfish. J. Bacteriol. 194 (3): 740-741 (2012).

Tekedar, H.C., A. Karsi, A.F. Gillaspy, D.W. Dyer, N.R. Benton, J. Zaitshik, S. Vamenta, M.M. Banes, N. Gülsoy, M. Aboko-Cole, G.C. Waldbieser, and M.L. Lawrence.  Genome Sequence of the fish pathogen Flavobacterium columnare ATCC 49512.  J. Bacteriol. 194 (10): 2763-2764 (2012).

Scott II, E, and D.W. Dyer. Divergence of the SigB regulon and pathogenesis of    the Bacillus cereus sensu lato group.  BMC Genomics 13: 564 (2012).

Robinson, C.M., G. Singh, J.Y. Lee, S. Dehghan, J. Rajaiya, E.B. Liu, M.A. Yousuf, R.A. Betensky, M.S. Jones, D.W. Dyer, D. Seto and J. Chodosh. Molecular evolution of human adenoviruses. Nature Sci. Rep. May 9; 3:1812 (2013); PMID: 23657240.

Jackson, L.A., J. Pan, M.W. Day and D.W. Dyer. Control of RNA stability by NrrF, an iron-regulated small RNA in Neisseria gonorrhoeae. J. Bacteriol. 2013 Sep 13. [Epub ahead of print] PMID: 24039262.

Dehghan, S., J. Seto, M.S. Jones, D.W Dyer, J. Chodosh and D. Seto. Simian adenovirus type 35 has a recombinant genome comprising human and simian adenovirus sequences, which predicts its potential emergence as a human respiratory pathogen. Virology 2013 Dec; 447(1-2):265-73. doi: 10.1016/j.virol.2013.09.009. Epub 2013 Oct 8.

Chavez-Bueno S, M. Day M, I. Toby, D. Akins, and D.W. Dyer. Genome Sequence of Multi-Drug Resistant Escherichia coli ST 131 Causing Neonatal Early-Onset Sepsis. Genome Announcements (in press, 2014).

Day, M., M. Ibrahim, D.W. Dyer and L. Bulla. Genome Sequence of Bacillus thuringiensis subsp. kurstaki Strain HD-1. Genome Announcements (submitted, 2014).

Toby, I., and D.W. Dyer. Divergence of protein-coding capacity and regulation in the Bacillus cereus sensu lato group. BMC Bioinformatics (submitted, 2014).