@article{troxell_petri_daron_pereira_mendoza_hassan_koci_2015, title={Poultry Body Temperature Contributes to Invasion Control through Reduced Expression of Salmonella Pathogenicity Island 1 Genes in Salmonella enterica Serovars Typhimurium and Enteritidis}, volume={81}, ISSN={0099-2240 1098-5336}, url={http://dx.doi.org/10.1128/AEM.02622-15}, DOI={10.1128/aem.02622-15}, abstractNote={ABSTRACT Salmonella enterica serovars Typhimurium (S. Typhimurium) and Enteritidis (S. Enteritidis) are foodborne pathogens, and outbreaks are often associated with poultry products. Chickens are typically asymptomatic when colonized by these serovars; however, the factors contributing to this observation are uncharacterized. Whereas symptomatic mammals have a body temperature between 37°C and 39°C, chickens have a body temperature of 41°C to 42°C. Here, in vivo experiments using chicks demonstrated that numbers of viable S. Typhimurium or S. Enteritidis bacteria within the liver and spleen organ sites were ≥4 orders of magnitude lower than those within the ceca. When similar doses of S. Typhimurium or S. Enteritidis were given to C3H/HeN mice, the ratio of the intestinal concentration to the liver/spleen concentration was 1:1. In the avian host, this suggested poor survival within these tissues or a reduced capacity to traverse the host epithelial layer and reach liver/spleen sites or both. Salmonella pathogenicity island 1 (SPI-1) promotes localization to liver/spleen tissues through invasion of the epithelial cell layer. Following in vitro growth at 42°C, SPI-1 genes sipC, invF, and hilA and the SPI-1 rtsA activator were downregulated compared to expression at 37°C. Overexpression of the hilA activators fur, fliZ, and hilD was capable of inducing hilA-lacZ at 37°C but not at 42°C despite the presence of similar levels of protein at the two temperatures. In contrast, overexpression of either hilC or rtsA was capable of inducing hilA and sipC at 42°C. These data indicate that physiological parameters of the poultry host, such as body temperature, have a role in modulating expression of virulence.}, number={23}, journal={Applied and Environmental Microbiology}, publisher={American Society for Microbiology}, author={Troxell, Bryan and Petri, Nicholas and Daron, Caitlyn and Pereira, Rafaela and Mendoza, Mary and Hassan, Hosni M. and Koci, Matthew D.}, editor={Elkins, C. A.Editor}, year={2015}, month={Sep}, pages={8192–8201} }
 @article{husain_jones-carson_liu_song_saah_troxell_mendoza_hassan_vazquez-torresa_2014, title={Ferric Uptake Regulator-Dependent Antinitrosative Defenses in Salmonella enterica Serovar Typhimurium Pathogenesis}, volume={82}, ISSN={["1098-5522"]}, DOI={10.1128/iai.01201-13}, abstractNote={ABSTRACT Herein we report an important role for the ferric uptake regulator (Fur) in the resistance of Salmonella enterica serovar Typhimurium to the reactive nitrogen species produced by inducible nitric oxide (NO) synthase in an NRAMP1r murine model of acute systemic infection. The expression of fur protected Salmonella grown under normoxic and hypoxic conditions against the bacteriostatic activity of NO. The hypersusceptibility of fur-deficient Salmonella to the cytotoxic actions of NO coincides with a marked repression of respiratory activity and the reduced ability of the bacteria to detoxify NO. A fur mutant Salmonella strain contained reduced levels of the terminal quinol oxidases of the electron transport chain. Addition of the heme precursor δ-aminolevulinic acid restored the cytochrome content, respiratory activity, NO consumption, and wild-type growth in bacteria undergoing nitrosative stress. The innate antinitrosative defenses regulated by Fur added to the adaptive response associated with the NO-detoxifying activity of the flavohemoprotein Hmp. Our investigations indicate that, in addition to playing a critical role in iron homeostasis, Fur is an important antinitrosative determinant of Salmonella pathogenesis.}, number={1}, journal={INFECTION AND IMMUNITY}, author={Husain, Maroof and Jones-Carson, Jessica and Liu, Lin and Song, Miryoung and Saah, J. Royden and Troxell, Bryan and Mendoza, Mary and Hassan, Hosni and Vazquez-Torresa, Andres}, year={2014}, month={Jan}, pages={333–340} }
 @misc{troxell_yang_2013, title={Metal-dependent gene regulation in the causative agent of Lyme disease}, volume={3}, journal={Frontiers in Cellular and Infection Microbiology}, author={Troxell, B. and Yang, X. F.}, year={2013} }
 @article{troxell_fink_porwollik_mcclelland_hassan_2011, title={The Fur regulon in anaerobically grown Salmonella enterica sv. Typhimurium: identification of new Fur targets}, volume={11}, ISSN={["1471-2180"]}, DOI={10.1186/1471-2180-11-236}, abstractNote={Abstract Background The Ferric uptake regulator (Fur) is a transcriptional regulator that controls iron homeostasis in bacteria. Although the regulatory role of Fur in Escherichia coli is well characterized, most of the studies were conducted under routine culture conditions, i.e., in ambient oxygen concentration. To reveal potentially novel aspects of the Fur regulon in Salmonella enterica serovar Typhimurium under oxygen conditions similar to that encountered in the host, we compared the transcriptional profiles of the virulent wild-type strain (ATCC 14028s) and its isogenic Δ fur strain under anaerobic conditions. Results Microarray analysis of anaerobically grown Δ fur S . Typhimurium identified 298 differentially expressed genes. Expression of several genes controlled by Fnr and NsrR appeared to be also dependent on Fur. Furthermore, Fur was required for the activity of the cytoplasmic superoxide disumutases (MnSOD and FeSOD). The regulation of FeSOD gene, sodB , occurred via small RNAs (i.e., the ryhB homologs, rfrA and rfrB ) with the aid of the RNA chaperone Hfq. The transcription of sodA was increased in Δ fur; however, the enzyme was inactive due to the incorporation of iron instead of manganese in SodA. Additionally, in Δ fur , the expression of the gene coding for the ferritin-like protein ( ftnB ) was down-regulated, while the transcription of the gene coding for the nitric oxide (NO · ) detoxifying flavohemoglobin ( hmpA ) was up-regulated. The promoters of ftnB and hmpA do not contain recognized Fur binding motifs, which indicated their probable indirect regulation by Fur. However, Fur activation of ftnB was independent of Fnr. In addition, the expression of the gene coding for the histone-like protein, H-NS ( hns ) was increased in Δ fur . This may explain the observed down-regulation of the tdc operon, responsible for the anaerobic degradation of threonine, and ftnB in Δ fur . Conclusions This study determined that Fur is a positive factor in ftnB regulation, while serving to repress the expression of hmpA . Furthermore, Fur is required for the proper expression and activation of the antioxidant enzymes, FeSOD and MnSOD. Finally, this work identified twenty-six new targets of Fur regulation, and demonstrates that H-NS repressed genes are down-regulated in Δ fur .}, journal={BMC MICROBIOLOGY}, author={Troxell, Bryan and Fink, Ryan C. and Porwollik, Steffen and McClelland, Michael and Hassan, Hosni M.}, year={2011}, month={Oct} }
 @article{fink_evans_porwollik_vazquez-torres_jones-carson_troxell_libby_mcclelland_hassan_2007, title={FNR is a global regulator of virulence and anaerobic metabolism in Salmonella enterica serovar typhimurium (ATCC 14028s)}, volume={189}, ISSN={["1098-5530"]}, DOI={10.1128/JB.00726-06}, abstractNote={ABSTRACT Salmonella enterica serovar Typhimurium must successfully transition the broad fluctuations in oxygen concentrations encountered in the host. In Escherichia coli, FNR is one of the main regulatory proteins involved in O2 sensing. To assess the role of FNR in serovar Typhimurium, we constructed an isogenic fnr mutant in the virulent wild-type strain (ATCC 14028s) and compared their transcriptional profiles and pathogenicities in mice. Here, we report that, under anaerobic conditions, 311 genes (6.80% of the genome) are regulated directly or indirectly by FNR; of these, 87 genes (28%) are poorly characterized. Regulation by FNR in serovar Typhimurium is similar to, but distinct from, that in E. coli. Thus, genes/operons involved in aerobic metabolism, NO· detoxification, flagellar biosynthesis, motility, chemotaxis, and anaerobic carbon utilization are regulated by FNR in a fashion similar to that in E. coli. However, genes/operons existing in E. coli but regulated by FNR only in serovar Typhimurium include those coding for ethanolamine utilization, a universal stress protein, a ferritin-like protein, and a phosphotransacetylase. Interestingly, Salmonella-specific genes/operons regulated by FNR include numerous virulence genes within Salmonella pathogenicity island 1 (SPI-1), newly identified flagellar genes (mcpAC, cheV), and the virulence operon (srfABC). Furthermore, the role of FNR as a positive regulator of motility, flagellar biosynthesis, and pathogenesis was confirmed by showing that the mutant is nonmotile, lacks flagella, is attenuated in mice, and does not survive inside macrophages. The inability of the mutant to survive inside macrophages is likely due to its sensitivity to the reactive oxygen species generated by NADPH phagocyte oxidase.}, number={6}, journal={JOURNAL OF BACTERIOLOGY}, author={Fink, Ryan C. and Evans, Matthew R. and Porwollik, Steffen and Vazquez-Torres, Andres and Jones-Carson, Jessica and Troxell, Bryan and Libby, Stephen J. and McClelland, Michael and Hassan, Hosni M.}, year={2007}, month={Mar}, pages={2262–2273} }