Toll-like receptors in CNS parasitic infections.

Parasite infections in the central nervous system (CNS) are a major cause of morbidity and mortality worldwide, second only to HIV infection. Finding appropriate therapeutic measures to control CNS parasite infections requires an understanding of the tissue-specific host response. CNS parasitic diseases are invariably associated with persistent T-helper 1 (Th1) cytokine-dependent proinflammatory responses.

Vaccination with a defined Francisella tularensis subsp. novicida pathogenicity island mutant (DeltaiglB) induces protective immunity against homotypic and heterotypic challenge.

Francisella tularensis, an intracellular Gram-negative bacterium, is the causative agent of tularemia and a potential bioweapon. Currently, there is no licensed vaccine against this organism. We have characterized the efficacy of a defined F.

Treatment and prevention of Candida albicans biofilms with caspofungin in a novel central venous catheter murine model of candidiasis.

Objectives: We sought to develop a novel model of central venous catheter (CVC)-associated candidiasis in mice and to use this model to examine the efficacy of caspofungin to treat and prevent Candida albicans biofilms in vivo.

Methods: We used catheterized mice, commercially available from the National Cancer Institute, to form C. albicans biofilms inside CVCs.

A genetically engineered live attenuated vaccine of Coccidioides posadasii protects BALB/c mice against coccidioidomycosis.

Coccidioidomycosis (also known as San Joaquin Valley fever) is an occupational disease. Workers exposed to outdoor dust which contains spores of the soil-inhabiting fungus have a significantly increased risk of respiratory infection. In addition, people with compromised T-cell immunity, the elderly, and certain racial groups, particularly African-Americans and Filipinos, who live in regions of endemicity in the southwestern United States have an elevated incidence of symptomatic infection caused by inhalation of spores of Coccidioides posadasii or Coccidioides immitis.

Targeted gene disruption in Francisella tularensis by group II introns.

Francisella tularensis is a highly infectious Gram-negative bacterium that is the causative agent of tularemia. Very little is known about the molecular mechanisms responsible for F. tularensis virulence, in part due to the paucity of genetic tools available for the study of F.

Design of a simple model of Candida albicans biofilms formed under conditions of flow: development, architecture, and drug resistance.

Candida albicans biofilms on most medical devices are exposed to a flow of body fluids that provide water and nutrients to the fungal cells. While C. albicans biofilms grown in vitro under static conditions have been exhaustively studied, the same is not true for biofilms developed under continuous flow of replenishing nutrients.

A limited role for antibody in protective immunity induced by rCPAF and CpG vaccination against primary genital Chlamydia muridarum challenge.

Mice deficient in B cells (micromT mice) were used to evaluate the role of antibody in enhanced chlamydial clearance and reduction of pathology afforded by vaccination with recombinant chlamydial protease-like activity factor (rCPAF). Enhanced, but comparable, chlamydial clearance was observed in micromT and wild-type (WT) mice after rCPAF+CpG vaccination. Chlamydia-induced pathology was present in mock-immunized animals, but at significantly greater levels in micromT than WT mice, whereas vaccinated micromT and WT mice exhibited similar reductions in pathology.

Oral live vaccine strain-induced protective immunity against pulmonary Francisella tularensis challenge is mediated by CD4+ T cells and antibodies, including immunoglobulin A.

Francisella tularensis is an intracellular gram-negative bacterium and the etiological agent of pulmonary tularemia. Given the high degrees of infectivity in the host and of dissemination of bacteria following respiratory infection, immunization strategies that target mucosal surfaces are critical for the development of effective vaccines against this organism. In this study, we have characterized the efficacy of protective immunity against pneumonic tularemia following oral vaccination with F.

Efficacy of a genetically engineered Candida albicans tet-NRG1 strain as an experimental live attenuated vaccine against hematogenously disseminated candidiasis.

We report on the efficacy of the genetically engineered Candida albicans tet-NRG1 strain as an experimental live, attenuated vaccine against disseminated candidiasis in both immunocompetent and immunodeficient mice mostly dependent on T-cell immunity. This experimental vaccination model may represent an important tool to unravel the mechanisms of protective immunity during candidiasis.

Effect of tunicamycin on Candida albicans biofilm formation and maintenance.

Background: Candida albicans is a common opportunistic pathogen of the human body and is the frequent causative agent of candidiasis. Typically, these infections are associated with the formation of biofilms on both host tissues and implanted biomaterials. As a result of the intrinsic resistance of C.

Expression and distribution of Toll-like receptors 11-13 in the brain during murine neurocysticercosis.

The functions of Toll-like receptors (TLRs) 11-13 in central nervous system (CNS) infections are currently unknown. Using a murine model of neurocysticercosis, we investigated the expression and distribution of TLRs 11-13 by using both gene specific real-time PCR analysis and in situ immunofluorescence microscopy in both control and neurocysticercosis brains. In the mock infected brain, mRNAs of TLRs 11-13 were constitutively expressed.

sodA is essential for virulence of Borrelia burgdorferi in the murine model of Lyme disease.

Borrelia burgdorferi, the causative agent of Lyme disease, has a limited set of genes to combat oxidative/nitrosative stress encountered in its tick vector or mammalian hosts. We inactivated the gene encoding for superoxide dismutase A (sodA, bb0153), an enzyme mediating the dismutation of superoxide anions and examined the in vitro and in vivo phenotype of the mutant. There were no significant differences in the in vitro growth characteristics of the sodA mutant compared with the control strains.

A simple and reproducible 96-well plate-based method for the formation of fungal biofilms and its application to antifungal susceptibility testing.

The incidence of fungal infections has increased significantly over the past decades. Very often these infections are associated with biofilm formation on implanted biomaterials and/or host surfaces. This has important clinical implications, as fungal biofilms display properties that are dramatically different from planktonic (free-living) populations, including increased resistance to antifungal agents.

Deletion of BBA64, BBA65, and BBA66 loci does not alter the infectivity of Borrelia burgdorferi in the murine model of Lyme disease.

Borrelia burgdorferi, the causative agent of Lyme disease, alters its gene expression in response to highly disparate environmental signals encountered in its tick vector versus vertebrate hosts. Whole-genome transcriptional profile analysis of B. burgdorferi, propagated in vitro under mammalian-host-specific conditions, revealed significant upregulation of several linear plasmid 54 (lp54)-encoded open reading frames (ORFs).

Characterization of the Francisella tularensis subsp. novicida type IV pilus.

Francisella tularensis causes the disease tularaemia. Type IV pili (Tfp) genes are present in the genomes of all F. tularensis subspecies.

Mast cells inhibit intramacrophage Francisella tularensis replication via contact and secreted products including IL-4.

Francisella tularensis is an intracellular, Gram-negative bacterium that is the causative agent of pulmonary tularemia. The pathogenesis and mechanisms related to innate resistance against F. tularensis are not completely understood.

CD4+ T cells are required during priming but not the effector phase of antibody-mediated IFN-gamma-dependent protective immunity against pulmonary Francisella novicida infection.

We have previously demonstrated the protective efficacy of intranasal vaccination with a defined Francisella tularensis subsp. novicida DeltaiglC mutant (KKF24) against pulmonary F. novicida U112 challenge.

A seed and feed model for the formation of Candida albicans biofilms under flow conditions using an improved modified Robbins device.

A variety of manifestations of Candida albicans infections are associated with the formation of biofilms on the surface of biomaterials. In order to maintain their niche these adherent populations need to withstand the continuous bathing action of physiological fluids (saliva, blood), which also provide water and nutrients to the fungal cells. Thus, it was the aim of this study to examine and further characterize the development of C.

Endogenous IFN-gamma production is induced and required for protective immunity against pulmonary chlamydial infection in neonatal mice.

Chlamydia trachomatis infection in neonates, not adults, has been associated with the development of chronic respiratory sequelae. Adult chlamydial infections induce Th1-type responses that subsequently clear the infection, whereas the neonatal immune milieu in general has been reported to be biased toward Th2-type responses. We examined the protective immune responses against intranasal Chlamydia muridarum challenge in 1-day-old C57BL/6 and BALB/c mice.

Antigen-specific CD4+ T cells produce sufficient IFN-gamma to mediate robust protective immunity against genital Chlamydia muridarum infection.

Chlamydia has been shown to evade host-specific IFN-gamma-mediated bacterial killing; however, IFN-gamma-deficient mice exhibit suboptimal late phase vaginal Chlamydia muridarum clearance, greater dissemination, and oviduct pathology. These findings introduce constraints in understanding results from murine chlamydial vaccination studies in context of potential implications to humans. In this study, we used mice deficient in either IFN-gamma or the IFN-gamma receptor for intranasal vaccination with a defined secreted chlamydial Ag, chlamydial protease-like activity factor (CPAF), plus CpG and examined the role of IFN-gamma derived from adoptively transferred Ag-specific CD4+ T cells in protective immunity against genital C.

Role of the BBA64 locus of Borrelia burgdorferi in early stages of infectivity in a murine model of Lyme disease.

Borrelia burgdorferi, the causative agent of Lyme disease, undergoes rapid adaptive gene expression in response to environmental signals encountered during different stages of its life cycle in the arthropod vector or the mammalian host. Among all the plasmid-encoded genes of B. burgdorferi, several linear plasmid 54 (lp54)-encoded open reading frames (ORFs) exhibit the greatest differential expression in response to mammalian host-specific temperature, pH, and other uncharacterized signals.

Lipidation of an FlrC-dependent protein is required for enhanced intestinal colonization by Vibrio cholerae.

Vibrio cholerae, the causative agent of cholera, has a sheathed, polar flagellum, and motility has been linked to virulence. An operon with two genes, flgO and flgP (VC2207 and VC2206), is positively regulated by FlrC, the activator of class III flagellar genes. Deletion of flgP results in a nonmotile phenotype, demonstrating the requirement of this gene for V.

Induction of cross-serovar protection against genital chlamydial infection by a targeted multisubunit vaccination approach.

An important consideration for antichlamydial vaccine development is the induction of cross-serovar protection, since multiple serovars (D to L) of Chlamydia trachomatis cause genital infections. We have shown previously that vaccination with C. trachomatis-derived recombinant chlamydial protease-like activity factor (rCPAF) induced significant earlier resolution of Chlamydia muridarum infection and reduced oviduct pathology.

Intranasal immunization with chlamydial protease-like activity factor and CpG deoxynucleotides enhances protective immunity against genital Chlamydia muridarum infection.

We have reported recently that intranasal (i.n.) vaccination with chlamydial protease-like activity factor (CPAF) and interleukin-12 (IL-12) enhances protective immunity against genital chlamydial challenge.