@article{khare_alali_zhang_hunter_pugh_fang_libby_adams_2010, title={Vaccination with attenuated Salmonella enterica Dublin expressing E coli O157:H7 outer membrane protein Intimin induces transient reduction of fecal shedding of E coli O157:H7 in cattle}, volume={6}, journal={BMC Veterinary Research}, author={Khare, S. and Alali, W. and Zhang, S. P. and Hunter, D. and Pugh, R. and Fang, F. C. and Libby, S. J. and Adams, L. G.}, year={2010} } @article{navarre_halsey_walthers_frye_mcclelland_potter_kenney_gunn_fang_libby_2005, title={Co-regulation of Salmonella enterica genes required for virulence and resistance to antimicrobial peptides by SlyA and PhoP/PhoQ}, volume={56}, ISSN={["1365-2958"]}, DOI={10.1111/j.1365-2958.2005.04553.x}, abstractNote={Analysis of the transcriptome of slyA mutant Salmonella enterica serovar Typhimurium revealed that many SlyA-dependent genes, including pagC, pagD, ugtL, mig-14, virK, phoN, pgtE, pipB2, sopD2, pagJ and pagK, are also controlled by the PhoP/PhoQ regulatory system. Many SlyA- and PhoP/PhoQ-co-regulated genes have functions associated with the bacterial envelope, and some have been directly implicated in virulence and resistance to antimicrobial peptides. Purified His-tagged SlyA binds to the pagC and mig-14 promoters in regions homologous to a previously proposed 'SlyA-box'. The pagC promoter lacks a consensus PhoP binding site and does not bind PhoP in vitro, suggesting that the effect of PhoP on pagC transcription is indirect. Stimulation of pagC expression by PhoP requires SlyA. Levels of SlyA protein and mRNA are not significantly changed under low-magnesium PhoP-inducing conditions in which pagC expression is profoundly elevated, however, indicating that the PhoP/PhoQ system does not activate pagC expression by altering SlyA protein concentration. Models are proposed in which PhoP may control SlyA activity via a soluble ligand or SlyA may function as an anti-repressor to allow PhoP activation. The absence of almost all SlyA-activated genes from the Escherichia coli K12 genome suggests that the functional linkage between the SlyA and PhoP/PhoQ regulatory systems arose as Salmonella evolved its distinctive pathogenic lifestyle.}, number={2}, journal={MOLECULAR MICROBIOLOGY}, author={Navarre, WW and Halsey, TA and Walthers, D and Frye, J and McClelland, M and Potter, JL and Kenney, LJ and Gunn, JS and Fang, FC and Libby, SJ}, year={2005}, month={Apr}, pages={492–508} } @article{bruno-barcena_andrus_libby_klaenhammer_hassan_2004, title={Expression of a heterologous manganese superoxide dismutase gene in intestinal lactobacilli provides protection against hydrogen peroxide toxicity}, volume={70}, ISSN={["1098-5336"]}, url={http://europepmc.org/abstract/med/15294805}, DOI={10.1128/AEM.70.8.4702-4710.2004}, abstractNote={In living organisms, exposure to oxygen provokes oxidative stress. A widespread mechanism for protection against oxidative stress is provided by the antioxidant enzymes: superoxide dismutases (SODs) and hydroperoxidases. Generally, these enzymes are not present in Lactobacillus spp. In this study, we examined the potential advantages of providing a heterologous SOD to some of the intestinal lactobacilli. Thus, the gene encoding the manganese-containing SOD (sodA) was cloned from Streptococcus thermophilus AO54 and expressed in four intestinal lactobacilli. A 1.2-kb PCR product containing the sodA gene was cloned into the shuttle vector pTRK563, to yield pSodA, which was functionally expressed and complemented an Escherichia coli strain deficient in Mn and FeSODs. The plasmid, pSodA, was subsequently introduced and expressed in Lactobacillus gasseri NCK334, Lactobacillus johnsonii NCK89, Lactobacillus acidophilus NCK56, and Lactobacillus reuteri NCK932. Molecular and biochemical analyses confirmed the presence of the gene (sodA) and the expression of an active gene product (MnSOD) in these strains of lactobacilli. The specific activities of MnSOD were 6.7, 3.8, 5.8, and 60.7 U/mg of protein for L. gasseri, L. johnsonii, L. acidophilus, and L. reuteri, respectively. The expression of S. thermophilus MnSOD in L. gasseri and L. acidophilus provided protection against hydrogen peroxide stress. The data show that MnSOD protects cells against hydrogen peroxide by removing O(2)(.-) and preventing the redox cycling of iron. To our best knowledge, this is the first report of a sodA from S. thermophilus being expressed in other lactic acid bacteria.}, number={8}, journal={APPLIED AND ENVIRONMENTAL MICROBIOLOGY}, author={Bruno-Barcena, JM and Andrus, JM and Libby, SL and Klaenhammer, TR and Hassan, HM}, year={2004}, month={Aug}, pages={4702–4710} } @article{halsey_vazquez-torres_gravdahl_fang_libby_2004, title={The ferritin-like Dps protein is required for Salmonella enterica serovar typhimurium oxidative stress resistance and virulence}, volume={72}, ISSN={["1098-5522"]}, DOI={10.1128/IAI.72.2.1155-1158.2004}, abstractNote={ABSTRACT Resistance to phagocyte-derived reactive oxygen species is essential for Salmonella enterica serovar Typhimurium pathogenesis. Salmonella can enhance its resistance to oxidants through the induction of specific genetic pathways controlled by SoxRS, OxyR, σ S , σ E , SlyA, and RecA. These regulons can be found in a wide variety of pathogenic and environmental bacteria, suggesting that evolutionarily conserved mechanisms defend against oxidative stress both endogenously generated by aerobic respiration and exogenously produced by host phagocytic cells. Dps, a ferritin-like protein found in many eubacterial and archaebacterial species, appears to protect cells from oxidative stress by sequestering iron and limiting Fenton-catalyzed oxyradical formation. In Escherichia coli and some other bacterial species, Dps has been shown to accumulate during stationary phase in a σ S -dependent fashion, bind nonspecifically to DNA, and form a crystalline structure that compacts and protects chromatin from oxidative damage. In the present study, we provide evidence that Dps protects Salmonella from iron-dependent killing by hydrogen peroxide, promotes Salmonella survival in murine macrophages, and enhances Salmonella virulence. Reduced numbers of dps mutant bacteria in the livers and spleens of infected mice are consistent with a role of Dps in protecting Salmonella from oxidative stress encountered during infection.}, number={2}, journal={INFECTION AND IMMUNITY}, author={Halsey, TA and Vazquez-Torres, A and Gravdahl, DJ and Fang, FC and Libby, SJ}, year={2004}, month={Feb}, pages={1155–1158} } @article{schapiro_libby_fang_2003, title={Inhibition of bacterial DNA replication by zinc mobilization during nitrosative stress}, volume={100}, ISSN={["0027-8424"]}, DOI={10.1073/pnas.1033133100}, abstractNote={Phagocytic cells inhibit the growth of intracellular pathogens by producing nitric oxide (NO). NO causes cell filamentation, induction of the SOS response, and DNA replication arrest in the Gram-negative bacterium Salmonella enterica . NO also induces double-stranded chromosomal breaks in replication-arrested Salmonella lacking a functional RecBCD exonuclease. This DNA damage depends on actions of additional DNA repair proteins, the RecG helicase, and RuvC endonuclease. Introduction of a recG mutation restores both resistance to NO and the ability of an attenuated recBC mutant Salmonella strain to cause lethal infection in mice, demonstrating that bacterial DNA replication is inhibited during host–pathogen interactions. Inhibition of DNA replication during nitrosative stress is invariably accompanied by zinc mobilization, implicating DNA-binding zinc metalloproteins as critical targets of NO-related antimicrobial activity.}, number={14}, journal={PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, author={Schapiro, JM and Libby, SJ and Fang, FC}, year={2003}, month={Jul}, pages={8496–8501} } @article{libby_lesnick_hasegawa_kurth_belcher_fierer_guiney_2002, title={Characterization of the spv locus in Salmonella enterica serovar Arizona}, volume={70}, DOI={10.1128/IAI.70.6.3290.3294.2002}, number={6}, journal={Infection and Immunity}, author={Libby, S. J. and Lesnick, M. and Hasegawa, P. and Kurth, M. and Belcher, C. and Fierer, J. and Guiney, D. G.}, year={2002}, pages={3290–3294} } @article{testerman_vazquez-torres_xu_jones-carson_libby_fang_2002, title={The alternative sigma factor sigma(E) controls antioxidant defences required for Salmonella virulence and stationary-phase survival}, volume={43}, ISSN={["1365-2958"]}, DOI={10.1046/j.1365-2958.2002.02787.x}, abstractNote={Bacteria must contend with conditions of nutrient limitation in all natural environments. Complex programmes of gene expression, controlled in part by the alternative sigma factors sigmaS (sigma38, RpoS) and sigmaH (sigma32, RpoH), allow a number of bacterial species to survive conditions of partial or complete starvation. We show here that the alternative sigma factor sigmaE (sigma24, RpoE) also facilitates the survival of Salmonella typhimurium under conditions of nutrient deprivation. Expression of the sigmaE regulon is strongly induced upon entry of Salmonella into stationary phase. A Salmonella mutant lacking sigmaE has reduced survival during stationary phase as well as increased susceptibility to oxidative stress. A Salmonella strain lacking both sigmaE and sigmaS is non-viable after just 24 h in stationary phase, but survival of these mutants is completely preserved under anaerobic stationary-phase conditions, suggesting that oxidative injury is one of the major mechanisms of reduced microbial viability during periods of nutrient deprivation. Moreover, the attenuated virulence of sigmaE-deficient Salmonella for mice can be largely restored by genetic abrogation of the host phagocyte respiratory burst, suggesting that the sigmaE regulon plays an important antioxidant role during Salmonella infection of mammalian hosts.}, number={3}, journal={MOLECULAR MICROBIOLOGY}, author={Testerman, TL and Vazquez-Torres, A and Xu, YS and Jones-Carson, J and Libby, SJ and Fang, FC}, year={2002}, month={Feb}, pages={771–782} } @article{wilson_libby_freet_boddicker_fahlen_jones_2001, title={Fis, a DNA nucleoid-associated protein, is involved in Salmonella typhimurium SPI-1 invasion gene expression}, volume={39}, number={1}, journal={Molecular Microbiology}, author={Wilson, R. L. and Libby, S. J. and Freet, A. M. and Boddicker, J. D. and Fahlen, T. F. and Jones, B. D.}, year={2001}, pages={79–88} } @article{allen_fedorka-cray_vazquez-torres_suyemoto_altier_ryder_fang_libby_2001, title={In Vitro and In Vivo Assessment of Salmonella enterica Serovar Typhimurium DT104 Virulence}, volume={69}, ISSN={0019-9567}, url={http://dx.doi.org/10.1128/iai.69.7.4673-4677.2001}, DOI={10.1128/IAI.69.7.4673-4677.2001}, abstractNote={Multidrug-resistant Salmonella enterica serovar Typhimurium phage type DT104 has become a widespread cause of human and other animal infection worldwide. The severity of clinical illness in S. enterica serovar Typhimurium DT104 outbreaks has led to the suggestion that this strain possesses enhanced virulence. In the present study, in vitro and in vivo virulence-associated phenotypes of several clinical isolates of S. enterica serovar Typhimurium DT104 were examined and compared to S. enterica serovar Typhimurium ATCC 14028s. The ability of these DT104 isolates to survive within murine peritoneal macrophages, invade cultured epithelial cells, resist antimicrobial actions of reactive oxygen and nitrogen compounds, and cause lethal infection in mice were assessed. Our results failed to demonstrate that S. enterica serovar Typhimurium DT104 isolates are more virulent than S. enterica serovar Typhimurium ATCC 14028s.}, number={7}, journal={Infection and Immunity}, publisher={American Society for Microbiology}, author={Allen, C. A. and Fedorka-Cray, P. J. and Vazquez-Torres, A. and Suyemoto, M. and Altier, C. and Ryder, L. R. and Fang, F. C. and Libby, S. J.}, year={2001}, month={Jul}, pages={4673–4677} } @article{libby_lesnick_hasegawa_weidenhammer_guiney_2000, title={The Salmonella virulence plasmid spv genes are required for cytopathology in human monocyte-derived macrophages}, volume={2}, ISSN={["1462-5814"]}, DOI={10.1046/j.1462-5822.2000.00030.x}, abstractNote={The pathogenesis of serious systemic Salmonella infections is characterized by survival and proliferation of bacteria inside macrophages. Infection of human monocyte-derived macrophages in vitro with S. typhimurium or S. dublin produces cytopathology characterized by detachment of cells that contain large numbers of proliferating bacteria. This cytopathology is dependent on the expression of the bacterial spv genes, a virulence locus previously shown to markedly enhance the ability of Salmonella to produce systemic disease. After 24 h of infection, macrophage cultures contain two populations of bacteria: (i) proliferating organisms present in a detached cell fraction; and (ii) a static bacterial population in macrophages remaining attached to the culture well. Mutations in either the essential transcriptional activator SpvR or the key SpvB protein markedly reduce the cytopathic effect of Salmonella infection. The spv-dependent cytopathology in macrophages exhibits characteristics of apoptosis, with release of nucleosomes into the cytoplasm, nuclear condensation and DNA fragmentation. The current findings suggest that the mechanism of the spv effect is through induction of increased cytopathology in host macrophages.}, number={1}, journal={CELLULAR MICROBIOLOGY}, author={Libby, SJ and Lesnick, M and Hasegawa, P and Weidenhammer, E and Guiney, DG}, year={2000}, month={Feb}, pages={49–58} } @article{watson_paulin_bland_libby_jones_wallis_1999, title={Differential regulation of enteric and systemic salmonellosis by slyA}, volume={67}, number={9}, journal={Infection and Immunity}, author={Watson, P. R. and Paulin, S. M. and Bland, A. P. and Libby, S. J. and Jones, P. W. and Wallis, T. S.}, year={1999}, pages={4950–4954} } @article{fernandez_xing_kapur_libby_barletta_moxley_1998, title={Regulation of the Escherichia coli sheA gene and characterization of its encoded hemolytic activity}, volume={168}, ISSN={["0378-1097"]}, DOI={10.1111/j.1574-6968.1998.tb13259.x}, abstractNote={Escherichia coli K-12 carries the cryptic hemolysin gene sheA which is under the control of positive and negative transcriptional regulators. The objectives of the present study were to further analyze the regulation of the sheA gene in E. coli, to compare the sheA genes from E. coli K-12 and a pathogenic E. coli strain, and to characterize the SheA hemolytic activity. Northern blot analysis demonstrated that the transcriptional regulator SlyA activates the E. coli K-12 sheA gene. The main transcriptional start site of the sheA gene was 56 nucleotides upstream from the start codon as determined by primer extension analysis. The sheA genes from E. coli K-12 and a pathogenic E. coli strain were identical. SheA hemolytic activity was cell associated and Ca2+ independent.}, number={1}, journal={FEMS MICROBIOLOGY LETTERS}, author={Fernandez, SV and Xing, J and Kapur, V and Libby, SJ and Barletta, RG and Moxley, RA}, year={1998}, month={Nov}, pages={85–90} } @article{buchmeier_bossie_chen_fang_guiney_libby_1997, title={SlyA, a transcriptional regulator of Salmonella typhimurium, is required for resistance to oxidative stress and is expressed in the intracellular environment of macrophages}, volume={65}, number={9}, journal={Infection and Immunity}, author={Buchmeier, N. and Bossie, S. and Chen, C. Y. and Fang, F. C. and Guiney, D. G. and Libby, S. J.}, year={1997}, pages={3725–3730} }