Miriam Golomb

Associate Professor of Biological Sciences

PhD, 1974 University of California - Berkeley

golombm@missouri.edu
573-882-9628
407 Tucker Hall

Research description

My laboratory studies the evolution and pathogenesis of Haemophilus influenzae, a gram-negative bacterium which causes diseases ranging from otitis media to meningitis. Nonencapsulated H. influenzae (NTHI) is an important cause of many respiratory illnesses, including those which complicate cystic fibrosis and chronic obstructive pulmonary disease. Genomic comparisons of nonencapsulated H influenzae and the sequenced, avirulent RdKW20 strain have revealed many putative virulence determinants, most of these imported from distantly related bacterial genomes. At present, my research includes a comparative study of H. influenzae genomes ( in collaboration with Dr. Arnold Smith’s lab, Seattle Biomedical Research Institute). We have recently discovered a chromosomal H. influenzae gene related to a multi-drug efflux pump component that has been transferred extremely recently (>98% DNA similarity) from the animal pathogen Pasteurella multocida, which diverged from H. influenzae (an exclusively human pathogen and commensal) an estimated 270 million years ago. This horizontal transfer event from P. multocida, which does not naturally colonize humans, may have occurred by an opportunistic infection after the domestication of its animal hosts as recently as 10,000 B.P.

In collaboration with Dr. Tom Phillips’ laboratory. I am currently investigating early events in H. influenzae colonization of respiratory cells, including function of the Lav protein of nonencapsulated H. influenzae, an outer membrane protein that belongs to a family of virulence-related autotransporters. A nearly identical lav gene (89% DNA identity) is found in Neisseria meningitidis, the agent of epidemic meningitis, which obtained it by lateral transfer from H. influenzae. Using tissue culture, we are looking at the role of Lav in the association of H. influenzae to cells of the human lower respiratory epithelium. The lav gene is phase-variable, mutating to the ON or OFF phase by gain or loss of tetranucleotide repeats within the 5’ end of the gene. Unlike most autotransporters, Lav is not proteolytically cleaved at the cell surface and remains full-length. We have constructed phase-locked mutants of several strains to investigate the role of Lav in cell adherence, autoaggregation, and biofilm formation.

In collaboration with Dr. Phillips’ laboratory to test the hypothesis that large microbes such as NTHI are transcytosed by M cells in the conjunctiva. NTHI were stained with fluorescein under conditions where they retain viability, and instilled into guinea pig conjunctivae. Confocal laser scanning microscopy showed that NTHi were selectively bound and translocated by conjunctival M cells, establishing conjunctival M cells as a potential port of entry for microbial pathogens.

Selected publications

Petris, C.K. , Golomb, M., and Phillips, T. E. 2007. Bacterial transcytosis across conjunctival M cells. Invest. Ophthalm. Vis. Sci. 48: 2172-2177.

Erwin, A.L., Nelson, K.L., Mutangadura, T. , Bothuis, P.J., Geelhood, J.L., Morlin, G., Unrath, W.C.T., Campos, J., Williams, B., Morlin, G., Crook, D.W., Farley, M.M., Jacobs, R.F., Muhlemann, K., Satola, S.W., von Alphen, L., Golomb, M., and Smith, A.L. 2005. Characterization of genetic and phenotypic diversity of invasive nontypeable Haemophilus influenzae. Infect. Immun. 73:5853-5863.

Kuwajima, V., Mandefro, A., Nelson, K.L., Smith, A.L., and M. Golomb. 2005. Genome Size As an Adaptation in Haemophilus influenzae: Genomic Comparison of the Sequenced Rd KW20 Strain with Its Archived Ancestors and Other Natural Isolates, submitted.

Williams, B. J., Golomb, M., Phillips, T., Brownlee, J., Olson, M.V., and Smith, A.L. 2002. Bacteriophage HP2 of Haemophilus influenzae. J. Bacteriol. 184: 6893-6905.

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