STEPHEN J. BILLINGTON  

Associate Professor
Ph.D. Monash University, 
Melbourne, Australia, 1993

Department of Veterinary Science and Microbiology
University of Arizona 
Tucson, AZ 85721

Phone  (520) 621-8641
Fax      (520) 621-6366
E-Mail  sbilling@u.arizona.edu

My primary area of research is the molecular genetics and pathogenesis of the opportunistic pathogen, Arcanobacterium pyogenes. This common inhabitant of mucosal surfaces of domestic animals, in combination with other invading microbes or physical trauma, can cause diseases as diverse as "summer" mastitis in cattle and polyarthritis in pigs.

Our research has focused on establishing genetic techniques for the manipulation of A. pyogenes and using these techniques to study virulence factors in this organism. In particular, we have determined that a hemolytic exotoxin, pyolysin, is an important virulence factor in experimental A. pyogenes infections in mice. Pyolysin is a novel member of the cholesterol dependent cytolysin family.

Like many opportunistic pathogens, A. pyogenes must tightly regulate its virulence factors. As such, I am interested in how expression of pyolysin and other A. pyogenes virulence factors are regulated. Pylosin expression appears to be regulated by a two-component regulatory system, PloR/PloS, which also reciprocally A. pyogenes proteases. Thus, the PloR/PloS system is potentially a global regulator of A. pyogenes virulence

As a commensal organism on domestic animals, A. pyogenes is routinely exposed to antibiotics, such as tetracycline derviatives and the macrolide, tylosin, which are fed to both cattle and swine for therapy and growth promotion. We have begun to characterize the genetic elements involved in resistance to antibiotics by A. pyogenes, with a view to determining their potential transfer to other bacteria.

MIC 205 General Microbiology
Selected lectures

MIC205B Microbiology Elements

VSC 595A Critical Evaluation of Scientific Literature

VSC 610 Advanced Topics in Microbiology and Cell Biology

Billington, S.J. and Jost, B.H. (2006). Multiple genetic elements carry the tetracycline resistance gene, tet(W) in the animal pathogen, Arcanobacterium pyogenes. Antimicrob. Agents Chemother. in press.

Myers, G.S., Rasko, D.A., Cheung, J.K., Ravel, J., Seshadri, R., Deboy, R.T., Ren, Q., Varga, J., Awad, M.M., Brinkac, L.M., Daugherty, S.C., Haft, D.H., Dodson, R.J., Madupu, R., Nelson, W.C., Rosovitz, M.J., Sullivan, S.A., Khouri, H., Dimitrov, G.I., Watkins, K.L., Mulligan, S., Benton, J., Radune, D., Fisher, D.J., Atkins, H.S., Hiscox, T., Jost, B.H., Billington, S.J., Songer, J.G., McClane, B.A., Titball, R.W., Rood, J.I., Melville, S.B. and Paulsen, I.T. (2006). Skewed genomic variability in strains of the toxigenic bacterial pathogen, Clostridium perfringens. Genome Res. in press.

Tambourgi, D.V., Fernandes Pedrosa, M.F., Gonçalves de Andrade, R.M., Billington, S.J., Griffiths, M. and van den Berg, C.W. (2006). Sphingomyelinases D induce direct association of C1q to the erythrocyte membrane causing complement mediated autologous hemolysis. Mol. Immunol. in press.

Jost, B.H., Billington, S.J., Trinh, H.T. and Songer, J.G. (2006). Association of genes encoding beta2 toxin and a collagen binding protein in Clostridium perfringens isolates of porcine origin. Vet. Microbiol 115: 173-182.

Jost, B.H. and Billington, S.J. (2005). Arcanobacterium pyogenes: molecular pathogenesis of an animal opportunist. Antonie van Leeuwenhoek 88: 87-102.

Jost, B.H., Billington, S.J., Trinh, H.T., Bueschel, D.M. and Songer, J.G. (2005). Atypical cpb2 genes, encoding beta2-toxin in Clostridium perfringens isolates of nonporcine origin. Infection and Immunity, 73:652–656. | Paper

Brands, D.A., Billington, S.J. Levine, J. and Joens, L.A. (2005). Genotypes and antibiotic resistance of Salmonella Newport isolates from U.S. market oysters. Foodborne Path. Dis. 2: 111 114.

Brands, D.A., Inman, A.E., Gerba, C.P., Mare, C.J., Billington, S.J., Saif, L.A., Levine, J.F. and Joens, L.A. (2005). The prevalence of Salmonella spp. in United States oysters. Appl. Environ. Microbiol. 71: 893-897.

Jost, B.H., Trinh, H.T., Songer, J.G. and Billington, S.J. (2004). Erm B is a determinant of tylosin resistance in Arcanobacterium pyogenes. Antimicrobial Agents and Chemotherapy, 48:721 727. | Paper

Jost, B.H., Trinh, H.T., Songer, J.G. and Billington, S.J. (2004). Ribosomal mutations in Arcanobacterium pyogenes confer a unique spectrum of macrolide resistance. Antimicrobial Agents and Chemotherapy, 48:1021 1023. | Paper

Van Meeteren, L.A., Frederiks, F., Giepmans, B.N., Fernandes Pedrosa, M.F., Billington, S.J., Jost, B.H., Tambourgi, D.V. and Moolenaar, W.H. (2004). Spider and bacterial sphingomyelinases D target cellular LPA receptors by hydrolyzing lysophosphatidylcholine. Journal of Biological Chemistry, 279:10833 10836. | Paper

Rudnick, S.T., Jost, B.H., Songer, J.G. and Billington, S.J. (2003). The gene encoding pyolysin, the pore-forming toxin of Arcanobacterium pyogenes, resides within a genomic islet flanked by essential genes. FEMS Microbiology Letters, 225:241-247. Paper

Esmay, P.A., Billington, S.J., Link, M.A., Songer, J.G. and Jost, B.H. (2003). The Arcanobacterium pyogenes collagen binding protein, CbpA, promotes adhesion to host cells. Infection and Immunity, 71:4368-4374. Paper

Jost, B.H., Field, A.C., Trinh, H.T., Songer, J.G. and Billington, S.J. (2003). Tylosin resistance in Arcanobacterium pyogenes is encoded by an Erm X determinant. Antimicrobial Agents and Chemotherapy, 47:3519 3524. | Paper

Jost, B.H., Trinh, H.T., Songer, J.G. and Billington, S.J. (2003). Immunization with genetic toxoids of the Arcanobacterium pyogenes cholesterol-dependent cytolysin, pyolysin, protects mice against infection. Infection and Immunity, 71:2966-2969. Paper

Bueschel, D.M., Jost, B.H., Billington, S.J., Trinh, H.T. and Songer J.G. (2003). Prevalence of cbp2, encoding beta2 toxin, in Clostridium perfringens field isolates: correlation of genotype with phenotype. Veterinary Microbiology, 94:121-129. Paper

Subbaiah, P.V., Billington, S.J., Jost, B.H., Songer, J.G. and Lange, Y. (2003). Sphingomyelinase D, a novel probe for cellular sphingomyelin: differential effects of sphingomyelinases C and D on cholesterol homeostasis in human skin fibroblasts. Journal of Lipid Research, 44:1574-1580. Paper

Billington, S.J., Songer, J.G. and Jost, B.H. (2002). Widespread distribution of a Tet W determinant among tetracycline resistant isolates of the animal pathogen, Arcanobacterium pyogenes. Antimicrobial Agents and Chemotherapy, 46:1281-1287. Paper

Billington S.J., Esmay, P.A., Songer, J.G. and Jost B.H. (2002). Identification and role in virulence of putative iron acquisition genes from Corynebacterium pseudotuberculosis. FEMS Microbiology Letters, 208:41-45. Paper

Trinh, H.T., Billington, S.J., Field, A.C., Songer, J.G. and Jost B.H. (2002). Susceptibility of Arcanobacterium pyogenes from different sources to tetracycline, macrolide and lincosamide antimicrobial agents. Veterinary Microbiology, 85:353-359. Paper

Jost, B.H., Songer, J.G. and Billington, S.J. (2002). Identification of a second Arcanobacterium pyogenes neuraminidase and involvement of neuraminidase activity in host cell adhesion. Infection and Immunity, 70:1106-1112. Paper

Billington, S.J., Post, K.W. and Jost, B.H. (2002). Isolation of Arcanobacterium (Actinomyces) pyogenes from cases of feline otitis externa and canine cystitis. Journal of Veterinary Diagnostic Investigation, 14:159-162.

Tambourgi, D.V., de Sousa da Silva, M., Billington, S.J., Goncalves de Andrade, R.M., MagnoliI, F.C., Songer J.G. and van den Berg, C.W. (2002). Mechanism of induction of complement susceptibility of erythrocytes by spider and bacterial sphingomyelinases. Immunology, 107:93-101. Paper

Billington, S.J., Songer, J.G. and Jost, B.H. (2001). Molecular characterization of the pore-forming toxin, pyolysin, a major virulence determinant of Arcanobacterium pyogenes. Veterinary Microbiology, 82:261-274. Paper

Jost, B.H., Songer, J.G., Billington, S.J. (2001). Cloning, expression and characterization of a neuraminidase gene from Arcanobacterium pyogenes. Infection and Immunity, 69:4430-4437. | Paper

Billington, S.J., Jost, B.H. and Songer, J.G. (2000). Thiol-activated cytolysins: structure, function and role in pathogenesis. FEMS Microbiology Letters, 182:197-205. Paper

Jost, B.H., Songer, J.G. and Billington, S.J. (1999). An Arcanobacterium (Actinomyces) pyogenes mutant deficient in production of the pore-forming cytolysin pyolysin has reduced virulence. Infection and Immunity, 67:1723-1728. Paper

Billington, S.J., Huggins A.S., Johannesen P., Crellin P.K., Cheung J., Katz M.E., Wright C.L., Haring, V. and Rood, J.I. (1999). Complete nucleotide sequence of the 27-kilobase virulence related locus (vrl) of Dichelobacter nodosus: evidence for extrachromosomal origin. Infection and Immunity, 67:1277-1286.

Billington, S.J., Wieckowski, E.U., Sarker, M.R., Bueschel, D., Songer, J.G. and McClane, B.A. (1998). Clostridium perfringens type E animal enteritis Isolates with highly conserved, silent enterotoxin gene sequences. Infection and Immunity, 66:4531-4536. Paper

Billington, S.J., Jost, B.H., Cuevas, W.A., Bright, K.R. and Songer, J.G. (1997). The Arcanobacterium (Actinomyces) pyogenes hemolysin, pyolysin, is a novel member of the thiol-activated cytolysin family. Journal of Bacteriology, 179:6100-6106. Paper