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Biomedical subjects

G Delogu

Publications and source records attributed to G Delogu.

At least 19 recordsLinked to original sources
PubMed2003

Pancuronium bromide, a non-depolarizing muscle relaxant which promotes apoptosis of blood lymphocytes in vitro.

BACKGROUND: Several compounds used in anesthesia practice have demonstrated to impair immune function and to influence the process of apoptotic death in T cell population following surgical trauma. We designed this study to test in vitro the impact of neuromuscular blocker, such as pancuronium, at clinically relevant concentration on lymphocyte apoptosis, death factor expression and mitochondrial function. METHODS: Following isolation, lymphocytes were incubated with pancuronium bromide at a clinically relevant concentration (0.136 micro mol l-1) for 3 h at 37 C in a 5% carbon-dioxide-humidified atmosphere and the frequency of apoptotic lymphocytes was then measured. We also investigated crucial steps in the apoptotic process, including Fas/Fas ligand (FasL) phenotype, intracellular expression of the interleukin-1beta-converting enzyme (ICE) p20, mitochondrial membrane potential (DeltaPsim), generation of mitochondrial reactive oxygen species, and glutathione (GSH) levels. Control experiments were performed incubating cells in the complete culture medium added with the dilution medium of the drug without addition of the drug. RESULTS: Expression of Fas, FasL and ICEp20 was six-fold, four-fold, and five-fold increased, respectively, among pancuronium-treated lymphocytes with respect to control cultures (P = 0.0001). The percentage of cells exhibiting either dissipation of mitochondrial membrane potential or increased production of reactive oxygen species was seven-fold increased following exposure to pancuronium compared with untreated lymphocytes (P = 0.0001). These findings were associated with a decrease in GSH level. In addition, the frequency of apoptotic cells was 10-fold greater among lymphocytes cultured in the presence of the drug with respect to control cultures. (P = 0.0001). CONCLUSION: Our data suggest an apoptogenic effect of pancuronium in vitro at clinically relevant concentration on peripheral blood lymphocytes. This could be implicated in the transient immune suppression following a surgical operation.

Adult↗
PubMed2001

Induction of a preferred sense of twist in flexible diphenyls by carbohydrate scaffolds. Synthesis of two "naked" ellagitannin analogous.

The synthesis of "naked" ellagitannin analogues 1 and 2, having a preferred sense of twist of the diphenyl moiety, with a rhamnose and a glucose template, is reported. A clear induction in the chirality of the diphenyl moiety, mediated through a 10-membered ring via ester linkages, was observed. The chiral scaffold of glucose (diequatorial 2,3-hydroxyl groups) exerts a remarkable stronger atropdiastereoselective effect onto the diphenoyl group than the rhamnose ring (axial-equatorial 2,3-hydroxyl groups), according to the Schmidt-Haslam hypothesis.

Biphenyl Compounds↗
PubMed2001

The heparin-binding haemagglutinin of M. tuberculosis is required for extrapulmonary dissemination.

Tuberculosis remains the world's leading cause of death due to a single infectious agent, Mycobacterium tuberculosis, with 3 million deaths and 10 million new cases per year. The infection initiates in the lungs and can then spread rapidly to other tissues. The availability of the entire M. tuberculosis genome sequence and advances in gene disruption technologies have led to the identification of several mycobacterial determinants involved in virulence. However, no virulence factor specifically involved in the extrapulmonary dissemination of M. tuberculosis has been identified to date. Here we show that the disruption of the M. tuberculosis or Mycobacterium bovis Bacille Calmette-Guérin (BCG) hbhA gene encoding the heparin-binding haemagglutinin adhesin (HBHA) markedly affects mycobacterial interactions with epithelial cells, but not with macrophage-like cells. When nasally administered to mice, the mutant strains were severely impaired in spleen colonization, but not in lung colonization. Coating wild-type mycobacteria with anti-HBHA antibodies also impaired dissemination after intranasal infection. These results provide evidence that adhesins such as HBHA are required for extrapulmonary dissemination, and that interactions with non-phagocytic cells have an important role in the pathogenesis of tuberculosis. They also suggest that antibody responses to HBHA may add to immune protection against tuberculosis.

Animals↗
PubMed2001

Mitochondrial perturbations and oxidant stress in lymphocytes from patients undergoing surgery and general anesthesia.

BACKGROUND: Previous studies have shown that a profound suppression of immune function transiently occurs in patients who undergo surgery under general anesthesia. The decline in the absolute counts of peripheral blood lymphocytes constitutes a major factor accounting for this immune defect, and recent evidence indicates that apoptosis plays a crucial role in determining postsurgical lymphocytopenia. HYPOTHESIS: An altered oxidation-reduction status of mitochondria may contribute through apoptosis to the loss of lymphocytes following surgical trauma and general anesthesia. DESIGN: We studied 16 patients with American Society of Anesthesiologists' physical status I or II who underwent elective surgery under general anesthesia. The data were collected prospectively. SETTING: University hospital. MAIN OUTCOME MEASURES: Samples of peripheral blood were drawn on the day before surgery and at 24 and 96 hours after the operation. Following lymphocyte isolation, the mitochondrial transmembrane potential was assessed by flow cytometry using 3,3'-dihexylocarbo-cyanine iodide, and stains with hydroethidine and 2'-7'-dichlorofluorescein diacetate were used to determine the generation of reactive oxygen species. The labeling of lymphocytes with monobromobimane was used to assess the presence of reduced glutathione. RESULTS: At 24 hours after surgery, we detected a significantly elevated frequency of peripheral blood lymphocytes (P =.002), which incorporated low levels of 3,3'-dihexylocarbo-cyanine iodide, compared with the preoperative period. At this same time point, the frequency of lymphocytes with the hydroethidine- and 2'-7'-dichlorofluorescein diacetate-positive phenotype was elevated compared with baseline levels. Conversely, at 24 hours after surgery, the frequency of cells that stained positive for glutathione was strongly decreased compared with preoperative values. Overall measurements returned to the baseline levels at 96 hours after surgery. CONCLUSION: The strict association we observed between the overproduction of reactive oxygen species and the disruption of the mitochondrial transmembrane potential supports the view that alterations in mitochondrial energy metabolism, paralleled by the presence of a pro-oxidant oxidation-reduction status, could be involved in the accelerated apoptotic loss of lymphocytes following surgical trauma and general anesthesia.

Anesthesia, General↗
PubMed2001

Electrospray ionisation tandem mass spectrometry in the characterisation of isomeric benzofurocoumarins.

A set of aminoalkoxy-substituted, differently annullated furocoumarins, differing in the position of the aminoalkoxy chain and in the unsaturation level of the fused ring, has been subjected to electron impact and electrospray ionisation (ESI) experiments. In order to achieve a distinct characterisation of isomeric compounds, which partially failed under electron impact conditions, collision-induced dissociation experiments were performed on protonated molecules. The breakdown curves obtained by varying the tickle voltage on an ion trap ESI instrument led to the desired characterisation.

Benzene↗
PubMed2001

Mycoplasma hominis and Trichomonas vaginalis symbiosis: multiplicity of infection and transmissibility of M. hominis to human cells.

We recently reported that most Trichomonas vaginalis isolates cultured in vitro are infected by Mycoplasma hominis. In this work, we have characterized some aspects of the relationships between the two microorganisms. PCR, cultivation, and immunological methods revealed that the number of M. hominis organisms carried by T. vaginalis in culture varied from isolate to isolate, suggesting a specific multiplicity of infection. Moreover, infected T. vaginalis isolates were able to pass bacteria not only to M. hominis-free protozoa, but also to human-derived epithelial cells. The in vitro transmission of the bacterium from T. vaginalis to both uninfected parasite isolates and human epithelial cells suggests a role for T. vaginalis as a carrier of the M. hominis infection in vivo.

Animals↗
PubMed2001

Bacillus cereus keratitis associated with contact lens wear.

OBJECTIVE: We report the first case of contact lens-related Bacillus cereus keratitis and ulcer associated with B. cereus contamination of the contact lens case. This is also the first study to investigate and establish the genetic identity of an organism isolated from the cornea and contact lens case in a patient with contact lens-associated keratitis. DESIGN: Case report. INTERVENTION AND TESTING: Conjunctival swabs and corneal scrapings from the left eye were inoculated for culture. The contact lens case was also cultured. Antibiotic susceptibility testing was determined by agar disk diffusion method. Initial treatment with topical ciprofloxacin and fortified tobramycin was given. Genetic analysis of the bacterial isolates was performed using polymerase chain reaction (PCR) with enterobacterial repetitive intergenic consensus primers (ERIC; ERIC-PCR). Susceptibility of B. cereus to heat and contact lens disinfecting solutions containing hydrogen peroxide, hydrogen peroxide-catalase, polyquaternium-1, and polyaminopropyl biguanide (PAPB) was tested. MAIN OUTCOME MEASURES: Clinical features, culture results, and antibiotic susceptibility testing were analyzed. The ERIC-PCR amplification products were visualized in ethidium bromide-stained agarose gel. Bacterial growth after exposure to heat and contact lens disinfecting solutions was assessed on blood agar plates. RESULTS: B. cereus was grown from the conjunctiva, corneal ulcer, and contact lens case. All isolates were sensitive to gentamicin, tobramycin, ciprofloxacin, clindamycin, and vancomycin. The corneal ulcer gradually healed over the next 6 days. Results of ERIC-PCR showed that the isolates from the cornea and contact lens case were indistinguishable, thus demonstrating the source of infecting organism to be the contaminated contact lens case. Exposure to a temperature of 80 degrees C for 20 minutes and incubation with hydrogen peroxide-catalase, polyquaternium-1, and PAPB for the minimum recommended time failed to kill B. cereus. Only exposure to hydrogen peroxide for 4 hours eradicated the organism. CONCLUSIONS: B. cereus should be considered a possible etiologic agent of contact lens-associated keratitis. Heat and many types of contact lens disinfecting solutions may be ineffective in eradicating B. cereus from contaminated contact lens cases. Only prolonged exposure to hydrogen peroxide appeared to be sporicidal to B. cereus in this study.

Bacillaceae Infections↗
PubMed2001

Circulating neutrophils exhibit enhanced apoptosis associated with mitochondrial dysfunctions after surgery under general anaesthesia.

BACKGROUND: Evidence suggests that apoptosis plays a main role in the postoperative changes detected in the polymorphonuclear neutrophil (PMN) population. Furthermore, recent studies have demonstrated that mitochondrial alterations constitute critical events of the apoptotic cascade. In this study we investigated whether apoptosis among neutrophils taken from patients undergoing surgical trauma could be associated with perturbation of mitochondrial transmembrane potential (deltapsim) and/or exaggerated production of mitochondrial reactive oxygen species (ROS). METHODS: Twenty-seven patients undergoing elective surgery under general anaesthesia were enrolled in the study. Peripheral blood samples were drawn one day before the operation and at 12 and 24 h after surgery. Apoptosis rate was assessed by staining neutrophils with 7-amino-actinomycin D (7-AAD) and by analysis by a FACScan flow cytometer. In order to evaluate deltapsim, cells were exposed to 3,3-dihexyloxacarbocyanine iodide [DiOC6(3)]; intracellular ROS was measured by means of hydroethidine (HE) and 2,7-diclorofluorescein diacetate (DCFH-DA), followed by analysis on a cytofluorometer. RESULTS: At 12 h following surgery we observed a significantly (P<0.05) increased frequency of apoptotic PMNs compared to that preoperatively (30.79+/-3.68% vs 7.40+/-0.69%). At this same time-point, the rate of neutrophils stained with HE, DCFH-DA and [DiOC6(3)] were significantly (P<0.05) higher compared to baseline (51.05+/-5.44%, 50.58+/-5.84% and 55.31+/-4.33% vs 20.17+/-2.38%, 19.59+/-2.03 and 25.43+/-2.71% respectively). Overall measurements returned to the preoperative values 24 h after surgery. CONCLUSION: These data suggest that surgery under general anaesthesia triggers in the immediate postoperative period pathways of PMN accelerated apoptosis associated with significant alterations in mitochondrial function.

Aged↗
PubMed2001

Interleukin-10 and apoptotic death of circulating lymphocytes in surgical/anesthesia trauma.

OBJECTIVE: To examine the relationship between circulating interleukin-10 (IL-10) and the occurrence of lymphocyte apoptosis after surgical/anesthesia trauma. METHODS: Data were collected prospectively on 18 adult patients undergoing elective major surgery. Blood sampling for assessment of lymphocyte apoptosis and IL-10 levels was performed on the day before surgery (t(0)) and at 24 and 96 hours after operation (t(1) and t(2), respectively). After lymphocyte isolation, quantification of apoptosis was made by staining apoptotic cells with 7-amino-actinomycin D. Plasma IL-10 concentrations were measured using enzyme-linked immunosorbent assay. RESULTS: A significantly increased frequency of apoptotic CD4(+) and CD8(+) cells (p < 0.05) was observed at t1 measurement (8.10% +/- 0.58% and 12.21% +/- 1.47% for CD4(+) and CD8(+), respectively) compared with preoperative values (1.53% +/- 0.38% and 1.32% +/- 0.45% for CD4(+) and CD8(+), respectively). Plasma IL-10 levels showed a significant elevation at both t(1) and t(2) times, peaking at t(1). At t(1), IL-10 levels were correlated with the frequency of CD4(+) and CD8(+) apoptotic lymphocytes (r = 0.78, p = 0.0005 for IL-10 vs. apoptotic CD4(+); r = 0.71, p = 0.003 for IL-10 vs. apoptotic CD8(+)). CONCLUSION: Surgical trauma is associated with a significant but transient increase in lymphocyte commitment to apoptosis and IL-10 production. The exact relationship linking the overproduction of IL-10 with lymphocyte apoptosis after a surgical operation is still elusive and requires further investigation.

Adult↗
PubMed2001

Molecular basis of rifampin and isoniazid resistance in Mycobacterium bovis strains isolated in Sardinia, Italy.

Fourteen of 22 (68%) Mycobacterium bovis strains isolated from cattle in Sardinia were found to be resistant to rifampin and isoniazid. Analysis of the rpoB and the katG, oxyR-ahpC, and inhA gene regions of these strains was performed in order to investigate the molecular basis of rifampin and isoniazid resistance, respectively. The most frequent mutation, encountered in 6 of 10 strains (60%), was in the rpoB gene; it occurred, at codon position 521 and resulted in leucine changed to proline. This suggests that codon 521 may be important for the development of rifampin resistance in M. bovis. Resistance to isoniazid is associated in Mycobacterium tuberculosis with a variety of mutations affecting one or more genes. Our results confirm the difficulty of interpreting the sequence variations observed in clinical strains of M. bovis. M. bovis strains isolated from the same geographic area showed similar mutations within the genes responsible for rifampin and isoniazid resistance. Our results represent the first study to elucidate the molecular genetic basis of drug resistance in M. bovis isolated from cattle.

Animals↗
PubMed2001

Evidence that mycobacterial PE_PGRS proteins are cell surface constituents that influence interactions with other cells.

The elucidation of the genomic sequence of Mycobacterium tuberculosis revealed the presence of a novel multigene family designated PE/PE_PGRS that encodes numerous, highly related proteins of unknown function. In this study, we demonstrate that a transposon insertion in a PE_PGRS gene (1818(PE_PGRS)) found in Mycobacterium bovis BCG Pasteur, which is the BCG homologue of the M. tuberculosis H37Rv gene Rv1818c, introduces new phenotypic properties to this BCG strain. These properties include dispersed growth in liquid medium and reduced infection of macrophages. Complementation of the 1818(PE_PGRS)::Tn5367 mutant with the wild-type gene restores both aggregative growth (clumping) in liquid medium and reestablishes infectivity of macrophages to levels equivalent to those for the parent BCG strain. Western blot analysis using antisera raised against the 1818(PE_PGRS) protein shows that PE_PGRS proteins are found in cell lysates of BCG and M. tuberculosis H37Ra and in the cell wall fraction of M. tuberculosis H37Rv. Moreover, immunofluorescent labeling of mycobacteria indicates that certain PE_PGRS proteins are localized at the cell surface of BCG and M. tuberculosis. Together these results suggest that certain PE_PGRS proteins may be found at the surface of mycobacteria and influence both cell surface interactions among mycobacteria as well as the interactions of mycobacteria with macrophages.

Adhesins, Bacterial↗
PubMed2001

By releasing ADP, Acanthamoeba castellanii causes an increase in the cytosolic free calcium concentration and apoptosis in wish cells.

The role played by soluble molecules that may participate in acanthamoebal cytopathogenicity has yet to be fully characterized. We demonstrate here that Acanthamoeba castellanii trophozoites constitutively release ADP in the medium. Cell-free supernatants prepared from A. castellanii, by interaction with specific P(2y2) purinoceptors expressed on the Wish cell membrane, caused a biphasic rise in [Ca(2+)](i), extensive cell membrane blebbing, cytoskeletal disorganization, and the breakdown of nuclei. Cell damage induced by amoebic supernatants was blocked by the P(2y2) inhibitor Suramin. The same results were found in Wish cells exposed to purified ADP. These findings suggest that pathogenic free-living A. castellanii may have a cytopathic effect on human epithelial cells through ADP release, by a process that begins with a rise of cytosolic free-calcium concentration, and culminates in apoptosis.

Acanthamoeba↗
PubMed2001

Comparative immune response to PE and PE_PGRS antigens of Mycobacterium tuberculosis.

Sequencing of the entire genome of Mycobacterium tuberculosis identified a novel multigene family composed of two closely related subfamilies designated PE and PE_PGRS. The major difference between these two families is the presence of a domain containing numerous Gly-Ala repeats extending to the C terminus of the PE_PGRS genes. We have used a representative PE_PGRS gene from M. tuberculosis, Rv1818c (1818PE_PGRS), and its amino-terminal PE region (1818PE), to investigate the immunological response to these proteins during experimental tuberculosis and following immunization with DNA constructs. During infection of mice with M. tuberculosis, a significant humoral immune response was observed against recombinant 1818PE_PGRS but not toward the 1818PE protein. Similarly, immunization with a 1818PE_PGRS DNA construct induced antibodies directed against 1818PE_PGRS but not against 1818PE proteins, and no humoral response was induced by 1818PE DNA. These results suggest that certain PE_PGRS genes are expressed during infection of the host with M. tuberculosis and that an antibody response is directed solely against the Gly-Ala-rich PGRS domain. Conversely, splenocytes from 1818PE-vaccinated mice but not mice immunized with 1818PE_PGRS secreted gamma interferon following in vitro restimulation and demonstrated protection in the mouse tuberculosis challenge model. These results suggest that the PE vaccine can elicit an effective cellular immune response and that immune recognition of the PE antigen is influenced by the Gly-Ala-rich PGRS domain.

Amino Acid Sequence↗
PubMed2001

[Proapoptotic effect of propofol on T cells].

BACKGROUND: Surgery and general anesthesia induce excessive apoptosis on peripheral lymphocytes and this phenomenon significantly contributes to the postoperative lymphocytopenia. However, the role played by anesthetic agents on this event remains to be elucidated. In this study we examined whether an anesthetic compound such as propofol is able to exert, in vitro, a proapoptotic effect on T cells. METHODS: Lymphocytes were isolated from heparinized venous blood in healthy volunteers and were incubated with propofol at clinically relevant concentration (5 mg/ml) and at 10 times this concentration (50 mg/ml). The counts of cells either bearing the Fas/FasL phenotype or expressing the intracellular Bcl2 protein were determined by means of flow cytometry. Assessment of lymphocytes undergoing apoptosis was made both by staining of apoptotic nuclei with propidium iodide (PI) and by phenotypic analysis of apoptotic cells with 7-amino-actinomycin D (7-AAD). RESULTS: Treated lymphocytes exhibit a significantly enhanced expression of Fas/FssL system associated with a decrease of Bcl2 expression at both 5 and 50 mg/ml propofol concentrations (p<0.05). On the other hand, the rate of apoptotic cells was not significantly different as compared to control in the absence of propofol. CONCLUSIONS: Propofol impairs, in vitro, both Fas/FasL and Bcl2 expressions on lymphocytes at clinically relevant concentrations but fails to induce apoptotic cell death. It is suggested that the antioxidative properties of the drug could inhibit some way the mechanisms by which mitochondrial free-radicals mediating apoptosis ultimately lead to cell death execution.

Anesthetics, Intravenous↗
PubMed2000

Apoptosis and surgical trauma: dysregulated expression of death and survival factors on peripheral lymphocytes.

BACKGROUND: Surgery and anesthesia cause depression of cell-mediated immunity in the postoperative period, including a reduction in the numbers of circulating lymphocytes. It has been claimed that this immunosuppression is associated with an increased incidence of postoperative infections. HYPOTHESIS: Lymphocytopenia following surgical trauma depends on a dysregulated expression of death/and survival factors associated with apoptosis that, in turn, interferes with the occurrence of postsurgical infections. DESIGN: Fifteen subjects undergoing elective surgery under general anesthesia entered the study. The data of the patients who had infections during the postoperative outcome were compared with the data of those who did not. The data were collected prospectively. MAIN OUTCOME MEASURES: Peripheral blood samples were drawn before the operation, and 24 hours and 96 hours after the operation. Lymphocytes were isolated and examined for quantification and phenotypic analysis of apoptosis using the 7-amino-actinomycin D method, as well as for Fas and Fas ligand, interleukin 1-converting enzyme p20/caspase-1, Bcl-2, and p35 expression. The rate of apoptotic cells was correlated with the incidence of postoperative infections. SETTING: University hospital. RESULTS: Twenty-four hours after surgery, CD4(+) and CD8(+) cells exhibited a significantly higher frequency of apoptosis as well as of Fas and Fas ligand and interleukin 1-converting enzyme p20/caspase-1 expressions than preoperatively. This increase was paralleled by a significant down-regulation of antiapoptotic factors such as Bcl-2. However, the expression of the proapoptotic factor p35 was reduced. In addition, we found a relationship between the rate of the apoptotic CD8(+) subset and the occurrence of infectious complications during the postoperative course. At 96 hours after surgery, the variables studied returned to the baseline levels. CONCLUSIONS: In the early postoperative period, surgical trauma under general anesthesia induces an intracellular perturbation on peripheral lymphocytes, resulting in both up-regulation of death-signaling factors and down-regulation of survival-signaling factors. The increased apoptosis of CD8(+) lymphocytes, but not of CD4(+) cells, seemed to be associated with a greater risk of postsurgical infections.

Analysis of Variance↗
PubMed2000

A pre-existing infection by Mycobacterium avium subsp. avium modulates anti-Cryptococcus neoformans and anti-Candida albicans activities in human macrophages.

Mycobacterium avium is a facultative intracellular microorganism, able to survive and multiply within mammalian macrophages by circumventing antimicrobial mechanisms. In this study we hypothesize that pre-existing M. avium infection could result in macrophage superinfections by other microorganisms. We found that 24 h after ingestion of M. avium at a low multiplicity of infection, macrophages are unable to efficiently produce superoxide anions when over-stimulated with phorbol esters, and that the generation of oxidative burst is only partially restored 72 h after bacteria ingestion. We also demonstrate that intracellular killing of Cryptococcus neoformans is markedly impaired in human macrophages that have previously ingested M. avium (but not other bacteria such as Escherichia coli). This inhibitory effect is observed with live mycobacteria, but not when heat-inactivated bacteria are ingested. In contrast, when Candida albicans is given to macrophages instead of C. neoformans, an enhancement of intracellular killing is observed, suggesting that cytocidal mechanisms other than respiratory burst are involved in the anti- Candidacidal activity of macrophages.

Candida albicans↗
PubMed2000

DNA vaccination against tuberculosis: expression of a ubiquitin-conjugated tuberculosis protein enhances antimycobacterial immunity.

Genetic immunization is a promising new technology for developing vaccines against tuberculosis that are more effective. In the present study, we evaluated the effects of intracellular turnover of antigens expressed by DNA vaccines on the immune response induced by these vaccines in a mouse model of pulmonary tuberculosis. The mycobacterial culture filtrate protein MPT64 was expressed as a chimeric protein fused to one of three variants of the ubiquitin protein (UbG, UbA, and UbGR) known to differentially affect the intracellular processing of the coexpressed antigens. Immunoblot analysis of cell lysates of in vitro-transfected cells showed substantial differences in the degradation rate of ubiquinated MPT64 (i.e., UbG64 < UbA64 < UbGR64). The specific immune response generated in mice correlated with the stability of the ubiquitin-conjugated antigen. The UbA64 DNA vaccine induced a weak humoral response compared to UbG64, and a mixed population of interleukin-4 (IL-4)- and gamma interferon (IFN-gamma)-secreting cells. Vaccination with the UbGR64 plasmid generated a strong Th1 cell response (high IFN-gamma, low IL-4) in the absence of a detectable humoral response. Aerogenic challenge of vaccinated mice with Mycobacterium tuberculosis indicated that immunization with both the UbA64- and UbGR64-expressing plasmids evoked an enhanced protective response compared to the vector control. The expression of mycobacterial antigens from DNA vaccines as fusion proteins with a destabilizing ubiquitin molecule (UbA or UbGR) shifted the host response toward a stronger Th1-type immunity which was characterized by low specific antibody levels, high numbers of IFN-gamma-secreting cells, and significant resistance to a tuberculous challenge.

Animals↗