@article{tan_havell_orndorff_shirwaiker_2017, title={Antibacterial efficacy and cytotoxicity of low intensity direct current activated silver-titanium implant system prototype}, volume={30}, ISSN={["1572-8773"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85009513848&partnerID=MN8TOARS}, DOI={10.1007/s10534-017-9993-1}, abstractNote={Silver-based devices activated by electric current are of interest in biomedicine because of their broad-spectrum antimicrobial activity. This study investigates the in vitro antibacterial efficacy and cytotoxicity of a low intensity direct current (LIDC)-activated silver-titanium implant system prototype designed for localized generation and delivery of silver ions at the implantation site. First, the antibacterial efficacy of the system was assessed against methicillin-resistant Staphylococcus aureus (MRSA) over 48 h at current levels of 3 and 6 µA in Mueller-Hinton broth. The cytotoxicity of the system was then evaluated over 48 h in two phases using an in vitro model with in which the activated electrodes were suspended in growth medium in a cell-seeded tissue culture plate. In phase-1, the system was tested on human osteosarcoma (MG-63) cell line and compared to titanium controls. In phase-2, the cytotoxicity characteristics were validated with normal human diploid osteoblast cells. The LIDC-activated system demonstrated high antimicrobial efficacy against MRSA, but was also toxic to human cells immediately surrounding the electrodes. The statistical analysis showed that the cytotoxicity was a result of the presence of silver, and the electric activation did not make it worse.}, number={1}, journal={BIOMETALS}, author={Tan, Zhuo and Havell, Edward A. and Orndorff, Paul E. and Shirwaiker, Rohan A.}, year={2017}, month={Feb}, pages={113–125} } @article{spears_havell_hamrick_goforth_levine_abraham_heiss_azadi_orndorff_2016, title={Listeria monocytogenes wall teichoic acid decoration in virulence and cell-to-cell spread}, volume={101}, ISSN={["1365-2958"]}, DOI={10.1111/mmi.13353}, abstractNote={Summary}, number={5}, journal={MOLECULAR MICROBIOLOGY}, author={Spears, Patricia A. and Havell, Edward A. and Hamrick, Terri S. and Goforth, John B. and Levine, Alexandra L. and Abraham, S. Thomas and Heiss, Christian and Azadi, Parastoo and Orndorff, Paul E.}, year={2016}, month={Sep}, pages={714–730} } @article{suyemoto_hamrick_spears_horton_washington_havell_borst_orndorff_2013, title={Extrauterine Listeriosis in the gravid mouse influences embryonic growth and development}, volume={8}, number={8}, journal={PLoS One}, author={Suyemoto, M. M. and Hamrick, T. S. and Spears, P. A. and Horton, J. R. and Washington, I. M. and Havell, E. A. and Borst, L. B. and Orndorff, P. E.}, year={2013} } @article{spears_suyemoto_hamrick_wolf_havell_orndorff_2011, title={In Vitro Properties of a Listeria monocytogenes Bacteriophage-Resistant Mutant Predict Its Efficacy as a Live Oral Vaccine Strain}, volume={79}, ISSN={["1098-5522"]}, DOI={10.1128/iai.05700-11}, abstractNote={ABSTRACT}, number={12}, journal={INFECTION AND IMMUNITY}, author={Spears, Patricia A. and Suyemoto, M. Mitsu and Hamrick, Terri S. and Wolf, Rebecca L. and Havell, Edward A. and Orndorff, Paul E.}, year={2011}, month={Dec}, pages={5001–5009} } @article{suyemoto_spears_hamrick_barnes_havell_orndorff_2010, title={Factors Associated with the Acquisition and Severity of Gestational Listeriosis}, volume={5}, ISSN={["1932-6203"]}, DOI={10.1371/journal.pone.0013000}, abstractNote={Gravid mammals are more prone to listeriosis than their nongravid counterparts. However, many features of the disease in gravid animals are not well defined. We determined, in mice, that increased susceptibility to lethal infection following oral inoculation begins surprisingly early in pregnancy and extends through embryonic development. Pregnancy did not demonstrably increase the spread of listeriae from the intestine to the liver and spleen in the initial 96 h period post inoculation. Consequently, it appeared that gravid animals were competent to contain an enteric infection, but in those instances where escape did occur, a lethal outcome was more likely. Interestingly, colonic colonization level and prevalence, measured 96 h post inoculation, was significantly higher in gravid individuals. In terms of human risk factors for listeriosis, our results suggest that the window of listeriosis susceptibility afforded by pregnancy may be open longer than previously appreciated. Our results also suggest that while gravid animals are competent to contain an enteric infection, enteric carriage rate may be more of a factor in defining disease incidence than previously considered.}, number={9}, journal={PLOS ONE}, author={Suyemoto, M. Mitsu and Spears, Patricia A. and Hamrick, Terri S. and Barnes, Jill A. and Havell, Edward A. and Orndorff, Paul E.}, year={2010}, month={Sep} } @article{spears_suyemoto_palermo_horton_hamrick_havell_orndorff_2008, title={A Listeria monocytogenes mutant defective in bacteriophage attachment is attenuated in orally inoculated mice and impaired in enterocyte intracellular growth}, volume={76}, ISSN={["0019-9567"]}, DOI={10.1128/IAI.00283-08}, abstractNote={ABSTRACT}, number={9}, journal={INFECTION AND IMMUNITY}, author={Spears, Patricia A. and Suyemoto, M. Mitsu and Palermo, Angela M. and Horton, John R. and Hamrick, Terri S. and Havell, Edward A. and Orndorff, Paul E.}, year={2008}, month={Sep}, pages={4046–4054} } @misc{orndorff_hamrick_smoak_havell_2006, title={Host and bacterial factors in listeriosis pathogenesis}, volume={114}, ISSN={["1873-2542"]}, DOI={10.1016/j.vetmic.2005.12.003}, abstractNote={Members of the Genus Listeria are ubiquitous environmental saprophytic microorganisms. If ingested they can cause a severe disseminated disease (listeriosis) that has a high mortality rate, the highest of any food-borne pathogen, even with antibiotic therapy. Central to the high mortality rate is the hallmark characteristic of the microorganism to grow intracellularly. The presence of listeriae in food processing plants has resulted in many outbreaks of human disease and large scale recalls of processed foods. Despite the ubiquity of the microorganism, the actual disease rate (those animals showing disease signs over those exposed) is quite low and disease is almost always associated with an underlying predisposition (pregnancy being the most common in otherwise normal individuals). There are many features of the pathogenesis of listeriosis that have remained mysterious despite the extensive use of the microorganism in the study of cell-mediated immunity and intracellular growth. Informational advances such as the sequence of the mouse and listerial genomes, and technical advances such as the discovery of listeria-susceptible mouse strains, may renew interest in the study of the natural pathogenesis of the disease. This may be further facilitated by studies that employ the natural inoculation route and mimic common predisposing conditions witnessed in victims of natural outbreaks.}, number={1-2}, journal={VETERINARY MICROBIOLOGY}, author={Orndorff, PE and Hamrick, TS and Smoak, IW and Havell, EA}, year={2006}, month={Apr}, pages={1–15} } @article{mccaffrey_fawcett_m o'riordan_lee_havell_brown_portnoy_2004, title={A specific gene expression program triggered by gram-positive bacteria in the cytosol}, volume={101}, ISSN={["0027-8424"]}, DOI={10.1073/pnas.0403215101}, abstractNote={ Innate and adaptive immunity depends critically on host recognition of pathogen-associated molecules. Toll-like receptors (TLRs) are key mediators of pathogen surveillance at the cell or phagocytic vacuole surface. However, mechanisms underlying recognition of pathogens in other cellular compartments remain unclear, and responses elicited by cytosolic challenge are poorly characterized. We therefore used mouse cDNA microarrays to investigate gene expression triggered by infection of bone marrow-derived macrophages with cytosol- and vacuole-localized Listeria monocytogenes ( Lm ), a model cytosolic pathogen. The resulting gene expression program included two basic categories of induced genes: an “early/persistent” cluster consistent with NF-κB-dependent responses downstream of TLRs, and a subsequent “late response” cluster largely composed of IFN-responsive genes (IRGs). The early/persistent cluster was observed upon infection with WT, heat-killed, or mutant Lm lacking listeriolysin O, the pore-forming hemolysin that promotes escape from phagocytic vacuoles. However, the IRG cluster depended on entry of WT Lm into the cytosol. Infection with listeriolysin O-expressing, cytosolic Bacillus subtilis ( Bs ) strikingly recapitulated the expression profile associated with WT Lm , including IRG induction. IRG up-regulation was associated with MyD88-independent induction of IFN-β transcription and activity. Whereas Staphylococcus aureus ( Sa ) lipoteichoic acid treatment confirmed that many late-response genes could also be stimulated through TLRs, our study identified a cytosol-specific transcriptional program independent of TLR signaling through MyD88. Further characterization of cytosolic surveillance pathway(s) and their points of convergence with TLR- and IFN-dependent pathways will enhance our understanding of the means by which mammals detect and respond to pathogens. }, number={31}, journal={PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, author={McCaffrey, RL and Fawcett, P and M O'Riordan and Lee, KD and Havell, EA and Brown, PO and Portnoy, DA}, year={2004}, month={Aug}, pages={11386–11391} } @article{hamrick_diaz_havell_horton_orndorff_2003, title={Influence of extracellular bactericidal agents on bacteria within macrophages}, volume={71}, ISSN={["0019-9567"]}, DOI={10.1128/IAI.71.2.1016-1019.2003}, abstractNote={ABSTRACT}, number={2}, journal={INFECTION AND IMMUNITY}, author={Hamrick, TS and Diaz, AH and Havell, EA and Horton, JR and Orndorff, PE}, year={2003}, month={Feb}, pages={1016–1019} } @article{hamrick_horton_spears_havell_smoak_orndorff_2003, title={Influence of pregnancy on the pathogenesis of listeriosis in mice inoculated intragastrically}, volume={71}, ISSN={["1098-5522"]}, DOI={10.1128/IAI.71.9.5202-5209.2003}, abstractNote={ABSTRACT}, number={9}, journal={INFECTION AND IMMUNITY}, author={Hamrick, TS and Horton, JR and Spears, PA and Havell, EA and Smoak, IW and Orndorff, PE}, year={2003}, month={Sep}, pages={5202–5209} } @article{harris_spears_havell_hamrick_horton_orndorff_2001, title={Characterization of Escherichia coli type 1 pilus mutants with altered binding specificities}, volume={183}, ISSN={["0021-9193"]}, DOI={10.1128/JB.183.13.4099-4102.2001}, abstractNote={ABSTRACT}, number={13}, journal={JOURNAL OF BACTERIOLOGY}, author={Harris, SL and Spears, PA and Havell, EA and Hamrick, TS and Horton, JR and Orndorff, PE}, year={2001}, month={Jul}, pages={4099–4102} } @article{hamrick_harris_spears_havell_horton_russell_orndorff_2000, title={Genetic characterization of Escherichia coli type 1 pilus adhesin mutants and identification of a novel binding phenotype}, volume={182}, ISSN={["0021-9193"]}, DOI={10.1128/JB.182.14.4012-4021.2000}, abstractNote={ABSTRACT}, number={14}, journal={JOURNAL OF BACTERIOLOGY}, author={Hamrick, TS and Harris, SL and Spears, PA and Havell, EA and Horton, JR and Russell, PW and Orndorff, PE}, year={2000}, month={Jul}, pages={4012–4021} } @article{hamrick_havell_horton_orndorff_2000, title={Host and bacterial factors involved in the innate ability of mouse macrophages to eliminate internalized unopsonized Escherichia coli}, volume={68}, ISSN={["0019-9567"]}, DOI={10.1128/IAI.68.1.125-132.2000}, abstractNote={ABSTRACT}, number={1}, journal={INFECTION AND IMMUNITY}, author={Hamrick, TS and Havell, EA and Horton, JR and Orndorff, PE}, year={2000}, month={Jan}, pages={125–132} } @article{li_havell_brown_cullen_2000, title={Woodchuck lymphotoxin-alpha, -beta and tumor necrosis factor genes: structure, characterization and biological activity}, volume={242}, ISSN={["0378-1119"]}, DOI={10.1016/S0378-1119(99)00494-1}, abstractNote={We cloned and characterized the woodchuck tumor necrosis factor (TNF) and lymphotoxin-alpha, -beta (LT-alpha, -beta) cDNAs, genes and proteins to facilitate study of the functions of these cytokines during the course of woodchuck hepatitis virus (WHV) infection. Woodchuck cDNA and genomic DNA libraries were screened with woodchuck-specific DNA probes to isolate the cDNA and gene clones for TNF, LT-alpha and LT-beta. The cDNAs for woodchuck TNF, LT-alpha and LT-beta code for proteins of 233, 205 and 310 amino acids respectively. The polypeptide encoded by each gene among woodchucks, humans and mice can differ: the human TNF, LT-alpha and LT-beta genes encode polypeptides of 233, 205 and 244 amino acids respectively, whereas the mouse TNF, LT-alpha and LT-beta genes encode polypeptides of 235, 202 and 306 amino acids respectively. In the woodchuck, there are four exons for TNF, four exons for LT-alpha and three exons for LT-beta. The RNA splicing patterns for TNF, LT-alpha and LT-beta genes are identical among woodchucks, humans and mice, except that the human LT-beta gene contains four exons. The woodchuck TNF gene promoter contains consensus sequences for binding of AP-1, AP-2, C/EBPbeta, CRE, Egr-1, Ets, NF-AT, NF-kappaB and SP-1 transcription factors. LT-alpha has AP-2, Ets, NF-kappaB, SP-1 and STAT binding sites, and LT-beta has Egr-1/SP-1, Ets and NF-kappaB binding sites. The bacterially expressed woodchuck TNF and LT-alpha proteins exhibited cytotoxic activities on both mouse L929B and woodchuck A2 cells in the presence of actinomycin D. The specific activities of TNF and LT-alpha were 2.62x10(8) units/mg and 2.22x10(3) units/mg respectively for L929B cells, and 1.05x10(9) units/mg and 3.56x10(4) units/mg respectively for A2 cells. However, only woodchuck TNF showed cytotoxic activity on human HepG2 cells, with a specific activity of 6.55x10(7) units/mg in the presence of actinomycin D. The data obtained from this study will be useful to future investigations of the TNF and LT antitumor and anti-viral activities, and their therapeutic potential in the woodchuck model for human hepatitis B virus (HBV).}, number={1-2}, journal={GENE}, author={Li, DH and Havell, EA and Brown, CL and Cullen, JM}, year={2000}, month={Jan}, pages={295–305} } @article{havell_beretich_carter_1999, title={The mucosal phase of Listeria infection}, volume={201}, ISSN={["0171-2985"]}, DOI={10.1016/S0171-2985(99)80056-4}, abstractNote={Listeria monocytogenes is an enteroinvasive bacterial pathogen of man and animals. Listeriae have been shown capable of infecting the host by translocating from the intestinal lumen through Peyer's Patches (PP), however, results of experiments now indicate that these facultative intracellular parasites may also translocate through PP-independent routes. With regards to this, on occasion we observed that listeriae were absent from the PP of mice inoculated intragastrically with L. monocytogenes, but were present in the mesenteric lymph nodes of these same mice. These observations suggested that PP were not necessary for listerial translocation from the intestinal lumen. Two experimental approaches were used to determine whether luminal listeriae could indeed infect the host through PP-independent routes. First, since it is known that: 1) following the intragastric inoculation of L. monocytogenes, listeriae rapidly transit the length of the gastrointestinal tract and reside in the colonic lumen for up to a week, 2) the colon lacks PP, and 3) the descending colon and rectum are drained exclusively by the caudal lymph node (CLN), it was determined whether colonic listeriae could access the CLN. Inoculation of listeriae into the rectum of mice resulted in the infection of the CLN which indicated that PP were not required for listerial translocation. Second, since germfree SCID mice lack PP, it was determined whether listeriae could translocate from the intestinal lumen and infect these immunoincompetent mice. Shortly after the intragastric inoculation of L. monocytogenes into germfree SCID mice, listeriae were found in the mesenteries, livers and spleens. These results also indicate that PP are not required for listerial translocation from the intestinal lumen. One possible route of translocation from the intestinal lumen might occur by listeriae entering enterocytes. Results were obtained showing that listeriae were capable of entering cultured mouse small intestine enterocytes. Internalized listeriae were observed to multiply and spread intracellularly between enterocytes.}, number={2}, journal={IMMUNOBIOLOGY}, author={Havell, EA and Beretich, GR and Carter, PB}, year={1999}, month={Dec}, pages={164–177} } @article{beretich_carter_havell_1998, title={Roles for tumor necrosis factor and gamma interferon in resistance to enteric listeriosis}, volume={66}, number={5}, journal={Infection and Immunity}, author={Beretich, G. R. and Carter, P. B. and Havell, E. A.}, year={1998}, pages={2368–2373} }