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PubMed2006

Porphyromonas gingivalis heat shock protein vaccine reduces the alveolar bone loss induced by multiple periodontopathogenic bacteria.

OBJECTIVES: Heat shock protein (HSP) can be utilized as a vaccine to cross-protect against multiple pathogenic species. The present study was performed to evaluate Porphyromonas gingivalis heat shock protein 60 (HSP60) as a vaccine candidate to inhibit multiple bacteria-induced alveolar bone loss. MATERIAL AND METHODS: Recombinant P. gingivalis HSP60 was produced and purified from P. gingivalis GroEL gene. Rats were immunized with P. gingivalis HSP60, and experimental alveolar bone loss was induced by infection with multiple periodontopathogenic bacteria. RESULTS: There was a very strong inverse relationship between postimmune anti-P. gingivalis HSP immunoglobulin G (IgG) levels and the amount of alveolar bone loss induced by either P. gingivalis or multiple bacterial infection (p=0.007). Polymerase chain reaction data indicated that the vaccine successfully eradicated the multiple pathogenic species. CONCLUSIONS: We concluded that P. gingivalis HSP60 could potentially be developed as a vaccine to inhibit periodontal disease induced by multiple pathogenic bacteria.

Actinobacillus Infections↗

PubMed1983

Pneumococcal meningitis and bacteraemia in Danish children 1969-1978. Serotypes, incidence and outcome.

The incidence of pneumococcal meningitis in Danish children during 1969-1978 was estimated to be 2.1/year/100,000 children from 0 to 14 years old. Fifty-five per cent of 146 children with pneumococcal meningitis and 61% of 61 with bacteraemia were below 2 years of age. Mortality from meningitis was 13% and from bacteraemia 7%. Of the children with meningitis, 14% had sequelae at the time of discharge from the hospital. Sequelae were not seen after bacteraemia. Among 277 pneumococcal isolates from spinal fluid and blood from Danish children during 1969-1978, serotypes 14, 18C, 6A + 6B, 23F, 7F and 19F, in that order of frequency, were the most common ones, accounting for 69% of all isolates. Serotypes included in current 14-valent pneumococcal polysaccharide vaccines made of 80% of all types, when types 6A and 6B are considered together (because it has been shown that they offer cross-protection).

Adolescent↗

PubMed1995

Clinical Importance of Salmonella Paratyphi A Infection to Enteric Fever in Nepal.

Background: Enteric fever in Nepal is caused by infection with Salmonella typhi or Salmonella paratyphi A. The clinical presentation of these two illnesses has never been compared in a population of travelers and expatriates. If the illnesses are clinically comparable, and if S. paratyphi A infection is sufficiently common, the choice of typhoid vaccine for Nepal may have to take into account the vaccine's efficacy in preventing infection with S. paratyphi A. Methods: NonNepalese patients presenting to the CIWEC Clinic with a history of 3 days of fever or greater were considered eligible for the study. Patients with positive blood or stool cultures for S. typhi or S. paratyphi A were entered into the study (along with three patients who had positive Widal titers only). A questionnaire was administered by a physician to determine signs and symptoms. Treatment with oral chloramphenicol was openly compared to treatment with oral ciprofloxacin. Results: Forty-five cases of enteric fever were diagnosed during the 2 years of the study. Infection with S. typhi accounted for 20 cases, and S. paratyphi A was isolated in 22 cases. The illnesses were clinically indistinguishable. Treatment with chloramphenicol and ciprofloxacin was clinically comparable. Conclusions: Infection with S. paratyphi A accounts for a significant percentage of enteric fever presentations among tourists in Nepal, and the illness is comparable to infection with S. typhi. Therefore, the choice of typhoid vaccine for long-term travelers or expatriates in Nepal should take into account the vaccine's potential ability to also prevent S. paratyphi A infection. The only typhoid vaccine that can currently offer this type of cross protection is the whole-cell killed preparation.

Journal Article↗

PubMed1998

Global eradication of rinderpest. Yea or nay?

Rinderpest is a scourge continuing to change the course of history. The German "Rinderpest" in English fails to convey the spectre of Death, Despair and Desolation long associated with the disease. Although the causal morbillivirus cross-protects against other morbillivirus, there is only one rinderpest serotype which is both immuno-suppressive and immunogenic. Safe vaccines induce lifelong protection in cattle. Transmission follows close contact between sick and healthy artiodactyls. Infectious periods are short and deaths may be curtailed by liberal fluid replacement therapy. Carriers do not exist. In other words rinderpest is a prime candidate for eradication. Why has it not happened? The major obstacle is "man's inhumanity to man". Rinderpest thrives in a milieu of armed conflict and fleeing refugee masses. Until world peace is secured, the "Nays" win the argument.

Animals↗

PubMed2000

Anaplasmosis control. Past, present, and future.

Control methods for anaplasmosis have not changed markedly during the past 50 years and include arthropod control, chemoprophylaxsis, vaccination, and maintenance of an Anaplasma-free herd. Control measures implemented vary with geographic location, and depend on availability, cost, and the feasibility of application. Vaccination has been an effective means of preventing outbreaks of anaplasmosis, but these vaccines, both live and inactivated, are dependent on bovine blood as the source of infection or antigen. Blood-derived vaccines are difficult to standardize and bear the risk of transmitting other bovine pathogens inapparent at the time of blood collection. Extensive purification is required to remove bovine cell membranes, which may cause side effects. Most importantly, geographic isolates of A. marginale are often not cross-protective. Development of a tick cell culture system for A. marginale shows promise as a source of antigen for development of an improved inactivated vaccine in the near future that is free from bovine pathogens. Development of an antigenically defined molecular vaccine appears to be a realistic goal, although further research is required to determine epitopes involved in both humoral and cellular immunity, to define antigenic variation during cyclic rickettsemia, and to develop effective delivery systems for optimization of the immune response.

Anaplasma↗

PubMed2000

Immunological control of ticks through vaccination with Boophilus microplus gut antigens.

The control of tick infestations and the transmission of tick-borne diseases remain a challenge for the scientific community. Traditional control methods have been only partially successful. Recently, vaccination with recombinant Boophilus microplus gut antigens has been shown to control tick infestations. Our Bm86-containing vaccine formulation (Gavac) has been effective for the control of artificial infestations of B. annulatus, B. decoloratus, and chemically sensitive and resistant B. microplus strains from Australia, Africa, America, and Iran. Preliminary results with Hyalomma spp. and Rhipicephalus spp. suggest partial cross protection. In field trials, vaccination with Gavac controlled B. microplus and B. annulatus infestations and reduced the transmission of babesiosis, resulting in important savings for the cattle industry. Different degrees of susceptibility to the vaccination with Bm86 and sequence variations in the Bm86 locus have been reported. The Bm95 antigen was isolated from the Argentinean Bm86-resistant B. microplus strain A. A Bm95-based vaccine was used to protect cattle against tick infestations under production conditions with similar results to that obtained with Gavac. The Bm95 antigen from strain A was able to protect against infestations with Bm86-sensitive and Bm86-resistant tick strains, thus suggesting that Bm95 could be a more universal antigen in protecting cattle against infestations by B. microplus strains from different geographical areas. These results clearly demonstrate the advantage and possibilities for the immunological control of ticks.

Animals↗

PubMed1985

Relationship between the resistance of cattle to Haemaphysalis longicornis and to Boophilus microplus.

Cattle that had been exposed to Haemaphysalis longicornis were as susceptible to Boophilus microplus as cattle that had never been exposed to either species of tick. Cattle with acquired resistance to both species ranked consistently for levels of resistance to each when infested separately. Concurrent infestation with H. longicornis had no effect on ranking for resistance to B. microplus. The coefficient of concordance between the rankings of individuals on their levels of resistance to both species of tick was positive, but was not statistically significant. We conclude that the tick antigens that stimulate host resistance are species-specific and do not cross protect. The apparent correlation in rankings for resistance to the 2 species may be a consequence of either an individual's immunological responsiveness to tick antigens or to non-specific host factors which determine levels of resistance. The apparent correlation suggests that co-selection for resistance to different tick species is practicable.

Animals↗

PubMed1982

Dynorphin is a specific endogenous ligand of the kappa opioid receptor.

In the guinea pig ileum myenteric plexus--longitudinal muscle preparation, dynorphin-(1--13) and the prototypical kappa agonist ethylketocyclazocine had equally poor sensitivity to naloxone antagonism and showed selective cross protection in receptor inactivation experiments with the alkylating antagonist beta-chlornaltrexamine. In binding assays with membranes from guinea pig brain, ethylketocyclazocine and dynorphin-(1--13) amide were more potent in displacing tritium-labeled ethylketocyclazocine than in displacing typical mu and delta opioid receptor ligands. In the two preparations studied, the dynorphin receptor appears to be the same as the kappa opioid receptor.

Analgesics, Opioid↗

PubMed1994

Starvation-Induced Stress Resistance in Lactococcus lactis subsp. lactis IL1403.

Carbohydrate-starved cultures of Lactococcus lactis subsp. lactis IL1403 showed enhanced resistance to heat, ethanol, acid, osmotic, and oxidative stresses. This cross-protection seems to be established progressively during the transitional growth phase, with maximum resistance occurring when cells enter the stationary phase. Chloramphenicol or rifamycin treatment does not abolish the development of a tolerant cell state but, on the contrary, seems to provoke this response in L. lactis subsp. lactis.

Journal Article↗

PubMed1997

The freeze-thaw stress response of the yeast Saccharomyces cerevisiae is growth phase specific and is controlled by nutritional state via the RAS-cyclic AMP signal transduction pathway.

The ability of cells to survive freezing and thawing is expected to depend on the physiological conditions experienced prior to freezing. We examined factors affecting yeast cell survival during freeze-thaw stress, including those associated with growth phase, requirement for mitochondrial functions, and prior stress treatment(s), and the role played by relevant signal transduction pathways. The yeast Saccharomyces cerevisiae was frozen at -20 degrees C for 2 h (cooling rate, less than 4 degrees C min-1) and thawed on ice for 40 min. Supercooling occurred without reducing cell survival and was followed by freezing. Loss of viability was proportional to the freezing duration, indicating that freezing is the main determinant of freeze-thaw damage. Regardless of the carbon source used, the wild-type strain and an isogenic petite mutant ([rho 0]) showed the same pattern of freeze-thaw tolerance throughout growth, i.e., high resistance during lag phase and low resistance during log phase, indicating that the response to freeze-thaw stress is growth phase specific and not controlled by glucose repression. In addition, respiratory ability and functional mitochondria are necessary to confer full resistance to freeze-thaw stress. Both nitrogen and carbon source starvation led to freeze-thaw tolerance. The use of strains affected in the RAS-cyclic AMP (RAS-cAMP) pathway or supplementation of an rca1 mutant (defective in the cAMP phosphodiesterase gene) with cAMP showed that the freeze-thaw response of yeast is under the control of the RAS-cAMP pathway. Yeast did not adapt to freeze-thaw stress following repeated freeze-thaw treatment with or without a recovery period between freeze-thaw cycles, nor could it adapt following pretreatment by cold shock. However, freeze-thaw tolerance of yeast cells was induced during fermentative and respiratory growth by pretreatment with H2O2, cycloheximide, mild heat shock, or NaCl, indicating that cross protection between freeze-thaw stress and a limited number of other types of stress exists.

Adaptation, Physiological↗

PubMed1999

The groESL chaperone operon of Lactobacillus johnsonii.

The Lactobacillus johnsonii VPI 11088 groESL operon was localized on the chromosome near the insertion element IS1223. The operon was initially cloned as a series of three overlapping PCR fragments, which were sequenced and used to design primers to amplify the entire operon. The amplified fragment was used as a probe to recover the chromosomal copy of the groESL operon from a partial library of L. johnsonii VPI 11088 (NCK88) DNA, cloned in the shuttle vector pTRKH2. The 2,253-bp groESL fragment contained three putative open reading frames, two of which encoded the ubiquitous GroES and GroEL chaperone proteins. Analysis of the groESL promoter region revealed three transcription initiation sites, as well as three sets of inverted repeats (IR) positioned between the transcription and translation start sites. Two of the three IR sets bore significant homology to the CIRCE elements, implicated in negative regulation of the heat shock response in many bacteria. Northern analysis and primer extension revealed that multiple temperature-sensitive promoters preceded the groESL chaperone operon, suggesting that stress protein production in L. johnsonii is strongly regulated. Maximum groESL transcription activity was observed following a shift to 55 degrees C, and a 15 to 30-min exposure of log-phase cells to this temperature increased the recovery of freeze-thawed L. johnsonii VPI 11088. These results suggest that a brief, preconditioning heat shock can be used to trigger increased chaperone production and provide significant cross-protection from the stresses imposed during the production of frozen culture concentrates.

Amino Acid Sequence↗

PubMed2001

Survival and heat resistance of Listeria monocytogenes after exposure to alkali and chlorine.

A strain of Listeria monocytogenes isolated from a drain in a food-processing plant was demonstrated, by determination of D values, to be more resistant to the lethal effect of heat at 56 or 59 degrees C following incubation for 45 min in tryptose phosphate broth (TPB) at pH 12.0 than to that of incubation for the same time in TPB at pH 7.3. Cells survived for at least 6 days when they were suspended in TPB at pHs 9.0, 10.0, and 11.0 and stored at 4 or 21 degrees C. Cells of L. monocytogenes incubated at 37 degrees C for 45 min and then stored for 48 or 144 h in TPB at pH 10.0 were more resistant to heat treatment at 56 degrees C than were cells stored in TPB at pH 7.3. The alkaline-stress response in L. monocytogenes may induce resistance to otherwise lethal thermal-processing conditions. Treatment of cells in 0.05 M potassium phosphate buffer (pH 7.00 +/- 0.05) containing 2.0 or 2.4 mg of free chlorine per liter reduced populations by as much as 1.3 log(10) CFU/ml, while treatment with 6.0 mg of free chlorine per liter reduced populations by as much as 4.02 log(10) CFU/ml. Remaining subpopulations of chlorine-treated cells exhibited some injury, and cells treated with chlorine for 10 min were more sensitive to heating at 56 degrees C than cells treated for 5 min. Contamination of foods by L. monocytogenes cells that have survived exposure to processing environments ineffectively cleaned or sanitized with alkaline detergents or disinfectants may have more severe implications than previously recognized. Alkaline-pH-induced cross-protection of L. monocytogenes against heat has the potential to enhance survival in minimally processed as well as in heat-and-serve foods and in foods on holding tables, in food service facilities, and in the home. Cells surviving exposure to chlorine, in contrast, are more sensitive to heat; thus, the effectiveness of thermal processing in achieving desired log(10)-unit reductions is not compromised in these cells.

Alkalies↗

PubMed2003

Thermal inactivation of susceptible and multiantimicrobial-resistant salmonella strains grown in the absence or presence of glucose.

The heat resistance of susceptible and multiantimicrobial-resistant Salmonella strains grown to stationary phase in glucose-free tryptic soy broth supplemented with 0.6% yeast extract (TSBYE-G; nonadapted), in regular (0.25% glucose) TSBYE, or in TSBYE-G with 1.00% added glucose (TSBYE+G; acid adapted) was determined at 55, 57, 59, and 61 degrees C. Cultures were heated in sterile 0.1% buffered peptone water (50 microl) in heat-sealed capillary tubes immersed in a thermostatically controlled circulating-water bath. Decimal reduction times (D values) were calculated from survival curves having r(2) values of >0.90 as a means of comparing thermal tolerance among variables. D(59 degrees C) values increased (P < 0.05) from 0.50 to 0.58 to 0.66 min for TSBYE-G, TSBYE, and TSBYE+G cultures, respectively. D(61 degrees C) values of antimicrobial-susceptible Salmonella strains increased (P < 0.05) from 0.14 to 0.19 as the glucose concentration increased from 0.00 to 1.00%, respectively, while D(61 degrees C) values of multiantimicrobial-resistant Salmonella strains did not differ (P > 0.05) between TSBYE-G and TSBYE+G cultures. When averaged across glucose levels and temperatures, there were no differences (P > 0.05) between the D values of susceptible and multiantimicrobial-resistant inocula. Collectively, D values ranged from 4.23 to 5.39, 1.47 to 1.81, 0.50 to 0.66, and 0.16 to 0.20 min for Salmonella strains inactivated at 55, 57, 59, and 61 degrees C, respectively. z(D) values were 1.20, 1.48, and 1.49 degrees C for Salmonella strains grown in TSBYE+G, TSBYE, and TSBYE-G, respectively, while the corresponding activation energies of inactivation were 497, 493, and 494 kJ/mol. Study results suggested a cross-protective effect of acid adaptation on thermal inactivation but no association between antimicrobial susceptibility and the ability of salmonellae to survive heat stress.

Animals↗

PubMed2004

Ethanol-mediated variations in cellular fatty acid composition and protein profiles of two genotypically different strains of Escherichia coli O157:H7.

Two strains of Escherichia coli O157:H7 were grown in tryptic soy broth (TSB, pH 7.1) supplemented with 0, 2.5, 5.0, 7.5, and 10% ethanol at 30 degrees C for up to 54 h. Growth rates in TSB supplemented with 0, 2.5, and 5.0% ethanol decreased with an increase in ethanol concentration. Growth was not observed in TSB supplemented with 7.5 or 10% ethanol. The pH of TSB containing 5.0% ethanol decreased to 5.8 within 12 h and then increased to 7.0 at 54 h. The ethanol content in TSB supplemented with 2.5 or 5.0% ethanol did not change substantially during the first 36 h of incubation but decreased slightly thereafter, indicating utilization or degradation of ethanol by both strains. Glucose was depleted in TSB supplemented with 0, 2.5, or 5.0% ethanol within 12 h. Cells grown under ethanol stress contained a higher amount of fatty acids. With the exceptions of cis-oleic acid and nonadecanoic acid, larger amounts of fatty acid were present in stationary-phase cells of the two strains grown in TSB supplemented with 5.0% ethanol for 30 h than in cells grown in TSB without ethanol for 22 h. The trans-oleic acid content was 10-fold higher in the cells grown in TSB with 5.0% ethanol than those grown in TSB without ethanol. In contrast, cis-oleic acid was not detected in ethanol-stressed cells but was present at concentrations of 0.32 and 0.36 mg/g of cells of the two strains grown in TSB without ethanol. Protein content was higher in ethanol-stressed cells than in nonstressed cells. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis protein profiles varied qualitatively as affected by the strain and the presence of ethanol in TSB. An ethanol-mediated protein (28 kDa) was observed in the ethanol-stressed cells but not in control cells. It is concluded that the two test strains of E. coli O157:H7 underwent phenotypic modifications in cellular fatty acid composition and protein profiles in response to ethanol stress. The potential for cross protection against subsequent stresses applied in food preservation technologies as a result of these changes is under investigation.

DNA, Bacterial↗

PubMed2005

Exposure to cadmium elevates expression of genes in the OxyR and OhrR regulons and induces cross-resistance to peroxide killing treatment in Xanthomonas campestris.

Cadmium is an important heavy metal pollutant. For this study, we investigated the effects of cadmium exposure on the oxidative stress responses of Xanthomonas campestris, a soil and plant pathogenic bacterium. The exposure of X. campestris to low concentrations of cadmium induces cross-protection against subsequent killing treatments with either H2O2 or the organic hydroperoxide tert-butyl hydroperoxide (tBOOH), but not against the superoxide generator menadione. The cadmium-induced resistance to peroxides is due to the metal's ability to induce increased levels of peroxide stress protective enzymes such as alkyl hydroperoxide reductase (AhpC), monofunctional catalase (KatA), and organic hydroperoxide resistance protein (Ohr). Cadmium-induced resistance to H2O2 is dependent on functional OxyR, a peroxide-sensing transcription regulator. Cadmium-induced resistance to tBOOH shows a more complex regulatory pattern. The inactivation of the two major sensor-regulators of organic hydroperoxide, OxyR and OhrR, only partially inhibited cadmium-induced protection against tBOOH, suggesting that these genes do have some role in the process. However, other, as yet unknown mechanisms are involved in inducible organic hydroperoxide protection. Furthermore, we show that the cadmium-induced peroxide stress response is mediated by the metal's ability to predominately cause an increase in intracellular concentrations of organic hydroperoxide and, in part, H2O2. Analyses of various mutants of peroxide-metabolizing enzymes suggested that this increase in organic hydroperoxide levels is, at least in part, responsible for cadmium toxicity in Xanthomonas.

Bacterial Proteins↗

PubMed2006

Molecular and genetic characterization of a novel nisin variant produced by Streptococcus uberis.

Streptococcus uberis is one of the principal causative agents of bovine mastitis. In this study, we report that S. uberis strain 42 produces a lantibiotic, nisin U, which is 78% identical (82% similar) to nisin A from Lactococcus lactis. The 15.6-kb nisin U locus comprises 11 open reading frames, similar in putative functionality but differing in arrangement from that of the nisin A biosynthetic cluster. The nisin U producer strain exhibits specific resistance (immunity) to nisin U and cross-resistance to nisin A, a finding consistent with the 55% sequence similarity of their respective immunity peptides. Homologues of the nisin U structural gene were identified in several additional S. uberis strains, and in each case cross-protective immunity was expressed to nisin A and to the other producers of nisin U and its variants. To our knowledge, this is the first report both of characterization of a bacteriocin by S. uberis, as well as of a member of the nisin family of peptides in a species other than L. lactis.

Amino Acid Sequence↗

PubMed2003

Molecular host-pathogen interaction in brucellosis: current understanding and future approaches to vaccine development for mice and humans.

Brucellosis caused by Brucella spp. is a major zoonotic disease. Control of brucellosis in agricultural animals is a prerequisite for the prevention of this disease in human beings. Recently, Brucella melitensis was declared by the Centers for Disease Control and Prevention to be one of three major bioterrorist agents due to the expense required for the treatment of human brucellosis patients. Also, the economic agricultural loss due to bovine brucellosis emphasizes the financial impact of brucellosis in society. Thus, vaccination might efficiently solve this disease. Currently, B. abortus RB51 and B. melitensis REV.1 are used to immunize cattle and to immunize goats and sheep, respectively, in many countries. However, these genetically undefined strains still induce abortion and persistent infection, raising questions of safety and efficiency. In fact, the REV.1 vaccine is quite virulent and apparently unstable, creating the need for improved vaccines for B. melitensis. In addition, Brucella spp. may or may not provide cross-protection against infection by heterologous Brucella species, hampering the acceleration of vaccine development. This review provides our current understanding of Brucella pathogenesis and host immunity for the development of genetically defined efficient vaccine strains. Additionally, conditions required for an effective Brucella vaccine strain as well as the future research direction needed to investigate Brucella pathogenesis and host immunity are postulated.

Animals↗

PubMed2006

Two complex, adenovirus-based vaccines that together induce immune responses to all four dengue virus serotypes.

Dengue virus infections can cause hemorrhagic fever, shock, encephalitis, and even death. Worldwide, approximately 2.5 billion people live in dengue-infested regions with about 100 million new cases each year, although many of these infections are believed to be silent. There are four antigenically distinct serotypes of dengue virus; thus, immunity from one serotype will not cross-protect from infection with the other three. The difficulties that hamper vaccine development include requirements of the natural conformation of the envelope glycoprotein to induce neutralizing immune responses and the necessity of presenting antigens of all four serotypes. Currently, the only way to meet these requirements is to use a mixture of four serotypes of live attenuated dengue viruses, but safety remains a major problem. In this study, we have developed the basis for a tetravalent dengue vaccine using a novel complex adenovirus platform that is capable of expressing multiple antigens de novo. This dengue vaccine is constructed as a pair of vectors that each expresses the premembrane and envelope genes of two different dengue virus serotypes. Upon vaccination, the vaccine expressed high levels of the dengue virus antigens in cells to mimic a natural infection and induced both humoral and cellular immune responses against multiple serotypes of dengue virus in an animal model. Further analyses show the humoral responses were indeed neutralizing against all four serotypes. Our studies demonstrate the concept of mimicking infections to induce immune responses by synthesizing dengue virus membrane antigens de novo and the feasibility of developing an effective tetravalent dengue vaccine by vector-mediated expression of glycoproteins of the four serotypes.

Adenoviridae↗