Bronchiseptica Infection Research Articles

Immunoprophylactic effects of shiitake mushroom (Lentinula edodes) against Bordetella bronchiseptica in mice

Antimicrobials are used as feed additives to improve growth performance and to prevent subclinical disease challenge in industrial animals. However, these drugs can lead to the development of resistant strains of bacteria. Shiitake mushrooms (SM) (Lentinula edodes) have long been popular as a health food in East Asia. Moreover, SM-derived polysaccharides are well-known as immunostimulants that possess antimicrobial properties. The aim of the present study was to evaluate the immunoprophylactic effects of SM against Bordetella bronchiseptica infection in mice as an initial step towards the development of eco-friendly feed additives to reduce the use of antimicrobials. Although SM had no effect on body weight gain under the un-infected conditions, SM alleviated progressive weight loss and helped in the recovery of body weight in B. bronchiseptica infected mice. Dietary supplementation with SM reinforced bacterial clearance in the infected mice. Of note, SM markedly increased the percentage of various T lymphocytes and the relative mRNA expression levels of tumor necrosis factor-α and interferon-γ in the bronchial lymph node early in the infection. Taken together, these findings suggest that SM could help in the improvement of body weight gain during B. bronchiseptica infection and may enhance the protective immune activity against a subclinical disease challenge, such as B. bronchiseptica infection in mice, probably by a strong stimulation of non-specific immune responses. Hence, SM may provide an alternative to reduce use of antimicrobials. Confirmation of the beneficial effects of SM as a feed additive is now required in industrial animals.

AroA deleted Bordetella bronchiseptica inspiring robust mucosal immune response and provide full protection against intranasal challenge

Bordetella bronchiseptica is a Gram-negative respiratory pathogen responsible for atrophic rhinitis and bronchopneumonia in swine. Several vaccines aimed at preventing B. bronchiseptica have been used, but a safe and efficient live vaccine for use in piglets remains elusive. In this study, we constructed an aroA-deleted B. bronchiseptica strain (QH0814) and evaluated its safety and protective efficiency in piglets. Lung lesion scores in QH0814-immunized piglets post-challenge were significantly lower than those in piglets immunized with the parent strain (P<0.05). Immunization with QH0814 induced a vigorous immune response, especially at the mucosal surface of the respiratory tract. IgA titers in bronchoalveolar lavage fluid (BALF) and serum were significantly higher in the QH0814-immunized group compared to the inactivated-vaccine-immunized group. Piglets immunized with QH0814 were better protected than those in the inactivated-vaccine and negative control groups. The clinical symptoms, histopathological changes and immune responses elicited in the piglets were recorded. The results of this study suggest that QH0814 was able to confer complete protection against B. bronchiseptica infection and could thus be used as a candidate attenuated live vaccine against B. bronchiseptica in piglets.

Phenotypic and Genomic Analysis of Hypervirulent Human-associated Bordetella bronchiseptica

BackgroundB. bronchiseptica infections are usually associated with wild or domesticated animals, but infrequently with humans. A recent phylogenetic analysis distinguished two distinct B. bronchiseptica subpopulations, designated complexes I and IV. Complex IV isolates appear to have a bias for infecting humans; however, little is known regarding their epidemiology, virulence properties, or comparative genomics.ResultsHere we report a characterization of the virulence of human-associated complex IV B. bronchiseptica strains. In in vitro cytotoxicity assays, complex IV strains showed increased cytotoxicity in comparison to a panel of complex I strains. Some complex IV isolates were remarkably cytotoxic, resulting in LDH release levels in A549 cells that were 10- to 20-fold greater than complex I strains. In vivo, a subset of complex IV strains was found to be hypervirulent, with an increased ability to cause lethal pulmonary infections in mice. Hypercytotoxicity in vitro and hypervirulence in vivo were both dependent on the activity of the bsc T3SS and the BteA effector. To clarify differences between lineages, representative complex IV isolates were sequenced and their genomes were compared to complex I isolates. Although our analysis showed there were no genomic sequences that can be considered unique to complex IV strains, there were several loci that were predominantly found in complex IV isolates.ConclusionOur observations reveal a T3SS-dependent hypervirulence phenotype in human-associated complex IV isolates, highlighting the need for further studies on the epidemiology and evolutionary dynamics of this B. bronchiseptica lineage.

&amp;lt;i&amp;gt;Bordetella bronchiseptica&amp;lt;/i&amp;gt; pneumonia in a woman with lymphoma: A case report

A 62-year-old woman with splenic marginal zone lymphoma presented with fever, cough and bilateral pneumonia 11 days after chemotherapy. A bronchoalveolar lavage showed numerous leukocytes and Gramnegative bacilli that were identified as Bordetella bronchiseptica in culture. An antibiotherapy with minocycline and ciprofloxacin helped her to stop coughing. This unusual micro-organism, which has mainly an animal reservoir, is a rarely cause of human infection, almost always in immunocompromised patients. The main problems in B. bronchiseptica infection are the difficulties of identification of this micro-organism and the recurrence of infection, which are a challenge for microbiologists and practitionners.

Differential Expression of Type III Effector BteA Protein Due to IS481 Insertion in Bordetella pertussis

Background Bordetella pertussis is the primary etiologic agent of the disease pertussis. Universal immunization programs have contributed to a significant reduction in morbidity and mortality of pertussis; however, incidence of the disease, especially in adolescents and adults, has increased in several countries despite high vaccination coverage. During the last three decades, strains of Bordetella pertussis in circulation have shifted from the vaccine-type to the nonvaccine-type in many countries. A comparative proteomic analysis of the strains was performed to identify protein(s) involved in the type shift.Methodology/Principal FindingProteomic analysis identified one differentially expressed protein in the B. pertussis strains: the type III cytotoxic effector protein BteA, which is responsible for host cell death in Bordetella bronchiseptica infections. Immunoblot analysis confirmed the prominent expression of BteA protein in the nonvaccine-type strains but not in the vaccine-type strains. Sequence analysis of the vaccine-type strains revealed an IS481 insertion in the 5′ untranslated region of bteA, −136 bp upstream of the bteA start codon. A high level of bteA transcripts from the IS481 promoter was detected in the vaccine-type strains, indicating that the transcript might be an untranslatable form. Furthermore, BteA mutant studies demonstrated that BteA expression in the vaccine-type strains is down-regulated by the IS481 insertion.Conclusion/SignificanceThe cytotoxic effector BteA protein is expressed at higher levels in B. pertussis nonvaccine-type strains than in vaccine-type strains. This type-dependent expression is due to an insertion of IS481 in B. pertussis clinical strains, suggesting that augmented expression of BteA protein might play a key role in the type shift of B. pertussis.

Evaluation of eight cases of confirmed Bordetella bronchiseptica infection and colonization over a 15-year period

We describe eight human cases of Bordetella bronchiseptica infection and colonization over a 15-year period. Amongst the eight patients, seven had significant underlying disease. Cat exposure was documented in three cases. Symptoms ranged from asymptomatic carriage to severe pneumonia. We could not identify a homogeneous pattern of clinical disease among symptomatic patients. Although B. bronchiseptica infection remains a rare clinical condition among humans, it should be considered as potentially pathogenic when found in airways of immunocompromised patients.

Identifying the Age Cohort Responsible for Transmission in a Natural Outbreak of Bordetella bronchiseptica

Identifying the major routes of disease transmission and reservoirs of infection are needed to increase our understanding of disease dynamics and improve disease control. Despite this, transmission events are rarely observed directly. Here we had the unique opportunity to study natural transmission of Bordetella bronchiseptica – a directly transmitted respiratory pathogen with a wide mammalian host range, including sporadic infection of humans – within a commercial rabbitry to evaluate the relative effects of sex and age on the transmission dynamics therein. We did this by developing an a priori set of hypotheses outlining how natural B. bronchiseptica infections may be transmitted between rabbits. We discriminated between these hypotheses by using force-of-infection estimates coupled with random effects binomial regression analysis of B. bronchiseptica age-prevalence data from within our rabbit population. Force-of-infection analysis allowed us to quantify the apparent prevalence of B. bronchiseptica while correcting for age structure. To determine whether transmission is largely within social groups (in this case litter), or from an external group, we used random-effect binomial regression to evaluate the importance of social mixing in disease spread. Between these two approaches our results support young weanlings – as opposed to, for example, breeder or maternal cohorts – as the age cohort primarily responsible for B. bronchiseptica transmission. Thus age-prevalence data, which is relatively easy to gather in clinical or agricultural settings, can be used to evaluate contact patterns and infer the likely age-cohort responsible for transmission of directly transmitted infections. These insights shed light on the dynamics of disease spread and allow an assessment to be made of the best methods for effective long-term disease control.

Bordetella bronchiseptica Bacteremia in a Patient with AIDS

Bordetella bronchiseptica bacteremia is often associated with various infection in animals. The majority of B bronchiseptica infections reported in humans are cases of pneumonia. Very few cases have been reported in patients with a history of acquired immune deficiency syndrome (AIDS). The patient described herein, who had a history of AIDS, was likely infected with B bronchiseptica as a result of his hemodialysis catheter. The patient was successfully treated with antibiotics without the removal of the catheter.

Kitten-transmitted Bordetella bronchiseptica infection in a patient receiving temozolomide for glioblastoma

Bordetella bronchiseptica is a gram negative coccobacillus that can be transmitted from domestic animals and cause severe infections in immunocompromised patients. A 56-year-old man with a left parietal glioblastoma was treated with resection, radiation and concomitant and adjuvant temozolomide chemotherapy. He received bevacizumab for progression, and dose dense metronomic temozolomide was added for additional progression. He developed chronic cough and was diagnosed with B. bronchiseptica infection. This is the first reported case of B. bronchiseptica infection in a patient receiving temozolomide. The infection was likely acquired from an infected kitten. Patients receiving temozolomide should be counseled on the risks of acquiring zoonotic infections, including B. bronchiseptica, from their pets.

The occurrence of Bordetella bronchiseptica in pigs with clinical respiratory disease

Between January 2003 and September 2008, 652 Bordetella bronchiseptica isolates were cultured from 3506 lung samples collected from pigs with respiratory disease. Over the 6-year period, the average isolation rate was 18.6%, making B. bronchiseptica the fourth most frequently isolated pathogenic bacterium from those lung samples. The isolation rates in different years and provinces ranged from 15.2% to 25.7% and 17.3% to 20.7%, respectively. There were significant influences of sampling month and pig age on bacterial isolation (P<0.05). Streptococcus suis (29.9%), Haemophilus parasuis (26.7%) and Escherichia coli (21.6%) were isolated most frequently in association with B. bronchiseptica. All 12 toxigenic Pasteurella multocida strains co-isolated with B. bronchiseptica from 63 cases of atrophic rhinitis were classified into serogroup D. The results suggest that B. bronchiseptica infection is highly prevalent in pig farms in China, and is often accompanied by co-infection with other bacteria.

Immune-Enhancing Effect of Fermented Maesil (Prunus mume Siebold &amp; Zucc.) with Probiotics against Bordetella bronchiseptica in Mice

Maesil (Prunus mume) has long been used as a traditional drug and healthy food in East Asian countries. It possesses a number of beneficial biological activities including potential antimicrobial effects against pathogens. Probiotics also have antibacterial effects. Moreover, some probiotics have an important role in regulating the immune system. The present study evaluated the immune enhancing effects of fermented Maesil with probiotics (Saccharomyces cerevisiae, Bacillus subtilis and Lactobacillus acidophilus) in mice, especially against Bordetella bronchiseptica, as an initial step towards the development of feed supplements for the promotion of immune activity and prevention of disease, especially in pigs. Continuous ingestion of fermented Maesil with probiotics markedly increased the macrophage ratio in peripheral blood and the T lymphocyte ratio in the spleen. In addition, antibody production against formalin-killed B. bronchiseptica significantly increased in the mice fed fermented Maesil compared with the control group. The number of leukocytes was significantly higher in the bronchio-alveolar lavage obtained from the fermented Maesil-fed animals compared to it in the control group at day 3 (maximal peak time) after experimental B. bronchiseptica infection. Moreover, at 7 day post-infection, relative messenger RNA expression levels of tumor necrosis factor- α and interferon-γ were significantly increased in splenocytes of mice fed fermented Maesil compared with those in the control group. Taken together, these findings suggest that feed containing fermented Maesil with probiotics enhances immune activity in mice, especially against B. bronchiseptica, via the potent stimulation of non-specific immune responses.

Association of Bordetella dermonecrotic toxin with the extracellular matrix

BackgroundBordetella dermonecrotic toxin (DNT) causes the turbinate atrophy in swine atrophic rhinitis, caused by a Bordetella bronchiseptica infection of pigs, by inhibiting osteoblastic differentiation. The toxin is not actively secreted from the bacteria, and is presumed to be present in only small amounts in infected areas. How such small amounts can affect target tissues is unknown.ResultsFluorescence microscopy revealed that DNT associated with a fibrillar structure developed on cultured cells. A cellular component cross-linked with DNT conjugated with a cross-linker was identified as fibronectin by mass spectrometry. Colocalization of the fibronectin network on the cells with DNT was also observed by fluorescence microscope. Several lines of evidence suggested that DNT interacts with fibronectin not directly, but through another cellular component that remains to be identified. The colocalization was observed in not only DNT-sensitive cells but also insensitive cells, indicating that the fibronectin network neither serves as a receptor for the toxin nor is involved in the intoxicating procedures. The fibronectin network-associated toxin was easily liberated when the concentration of toxin in the local environment decreased, and was still active.ConclusionsComponents in the extracellular matrix are known to regulate activities of various growth factors by binding and liberating them in response to alterations in the extracellular environment. Similarly, the fibronectin-based extracellular matrix may function as a temporary storage system for DNT, enabling small amounts of the toxin to efficiently affect target tissues or cells.

Bordetella pertussis Infection or Vaccination Substantially Protects Mice against B. bronchiseptica Infection

Although B. bronchiseptica efficiently infects a wide range of mammalian hosts and efficiently spreads among them, it is rarely observed in humans. In contrast to the many other hosts of B. bronchiseptica, humans are host to the apparently specialized pathogen B. pertussis, the great majority having immunity due to vaccination, infection or both. Here we explore whether immunity to B. pertussis protects against B. bronchiseptica infection. In a murine model, either infection or vaccination with B. pertussis induced antibodies that recognized antigens of B. bronchiseptica and protected the lower respiratory tract of mice against three phylogenetically disparate strains of B. bronchiseptica that efficiently infect naïve animals. Furthermore, vaccination with purified B. pertussis-derived pertactin, filamentous hemagglutinin or the human acellular vaccine, Adacel, conferred similar protection against B. bronchiseptica challenge. These data indicate that individual immunity to B. pertussis affects B. bronchiseptica infection, and suggest that the high levels of herd immunity against B. pertussis in humans could explain the lack of observed B. bronchiseptica transmission. This could also explain the apparent association of B. bronchiseptica infections with an immunocompromised state.

Bordetella bronchiseptica infection in cats. ABCD guidelines on prevention and management.

Bordetella bronchiseptica is a Gram-negative bacterium that colonises the respiratory tract of mammals and is considered to be a primary pathogen of domestic cats. It is sensible to consider B bronchiseptica as a rare cause of zoonotic infections. The bacterium is susceptible to common disinfectants. The bacterium is shed in oral and nasal secretions of infected cats. Dogs with respiratory disease are an infection risk for cats. The microorganism colonises the ciliated epithelium of the respiratory tract of the host, establishing chronic infections. A wide range of respiratory signs has been associated with B bronchiseptica infection, from a mild illness with fever, coughing, sneezing, ocular discharge and lymphadenopathy to severe pneumonia with dyspnoea, cyanosis and death. Bacterial culture and PCR lack sensitivity. Samples for isolation can be obtained from the oropharynx (swabs) or via transtracheal wash/ bronchoalveolar lavage. Antibacterial therapy is indicated, even if the signs are mild. Where sensitivity data are unavailable, tetracyclines are recommended. Doxycycline is the antimicrobial of choice. Cats with severe B bronchiseptica infection require supportive therapy and intensive nursing care. In some European countries an intranasal modified-live virus vaccine is available. The modified-live product is licensed for use as a single vaccination with annual boosters. Cats should not be routinely vaccinated against B bronchiseptica (non-core), since the infection generally causes only a mild disease.

Relapsing Peritonitis Caused by Bordetella bronchiseptica in Continuous Ambulatory Peritoneal Dialysis Patient: A Case Report

Bordetella (B) bronchiseptica is a common veterinary pathogen, but has rarely been implicated in human infections. Most patients with B. bronchiseptica infections are compromised clinically such as in patients with a malignancy, AIDS, malnutrition, or chronic renal failure. We experienced a case of relapsing peritonitis caused by B. bronchiseptica associated with continuous ambulatory peritoneal dialysis (CAPD). A 56-yr-old male, treated with CAPD due to end stage renal disease (ESRD), was admitted with complaints of abdominal pain and a turbid peritoneal dialysate. The culture of peritoneal dialysate identified B. bronchiseptica. The patient was treated with a combination of intraperitoneal antibiotics. There were two further episodes of relapsing peritonitis, although the organism was sensitive to the used antibiotics. Finally, the indwelling CAPD catheter was removed and the patient was started on hemodialysis. This is the first report of a B. bronchiseptica human infection in the Korean literature.

Performance of transport and selective media for swine Bordetella bronchiseptica recovery and it comparison to polymerase chain reaction detection

Three comparative assays were performed seeking to improve the sensitivity of the diagnosis of Bordetella bronchiseptica infection analyzing swine nasal swabs. An initial assay compared the recovery of B. bronchiseptica from swabs simultaneously inoculated with B. bronchiseptica and some interfering bacteria, immersed into three transport formulations (Amies with charcoal, trypticase soy broth and phosphate buffer according to Soerensen supplemented with 5% of bovine fetal serum) and submitted to different temperatures (10°C and 27°C) and periods of incubation (24, 72 and 120 hours). A subsequent assay compared three selective media (MacConkey agar, modified selective medium G20G and a ceftiofur medium) for their recovery capabilities from clinical specimens. One last assay compared the polymerase chain reaction to the three selective media. In the first assay, the recovery of B. bronchiseptica from transport systems was better at 27°C and the three formulations had good performances at this temperature, but the collection of qualitative and quantitative analysis indicated the advantage of Amies medium for nasal swabs transportation. The second assay indicated that MacConkey agar and modified G20G had similar results and were superior to the ceftiofur medium. In the final assay, polymerase chain reaction presented superior capability of B. bronchiseptica detection to culture procedures.

BORDETELLA BRONCHISEPTICA INFECTION IN AN IMMUNOCOMPROMISED PATIENT

INTRODUCTION: Pulmonary infections due to atypical organisms are often overlooked in immunosuppressed patients. We describe a case of Bordetella bronchiseptica infection in an immunocompromised patient.

CD11b is required for the resolution of inflammation induced by Bordetella bronchiseptica respiratory infection

CD11b is a cell surface receptor that contributes to many cellular processes which are involved in the generation of a protective immune response against pathogenic organisms. In this work, the natural host-pathogen model of murine Bordetella bronchiseptica infection was used to explore the role of CD11b in respiratory immunity. Following intranasal inoculation, CD11b-/- mice rapidly succumb to B. bronchiseptica respiratory infection, highlighting the prominent role of CD11b in the generation of a protective immune response in this model. CD11b appears to be required for both the control of bacterial numbers and the regulation of cellular responses in the lungs. An increased accumulation of neutrophils in the lungs of CD11b-/- mice as compared with wild-type mice suggests that CD11b contributes to the regulation of cellular responses to respiratory infection. This accumulation may be explained by a decrease in apoptosis that is observed in the absence of CD11b following cellular interactions with B. bronchiseptica. Interestingly, this role for CD11b in the regulation of cellular accumulation appears to be critically important for the resolution of damage associated with the type III secretion system (TTSS) of B. bronchiseptica. These data provide new insight into the key role CD11b plays in the resolution of damage in the lower respiratory tract, as well as the B. bronchiseptica virulence determinant that induces it.

BopC Is a Novel Type III Effector Secreted by Bordetella bronchiseptica and Has a Critical Role in Type III-dependent Necrotic Cell Death

In Bordetella bronchiseptica, the functional type III secretion system (TTSS) is required for the induction of necrotic cell death in infected mammalian cells. To identify the factor(s) involved in necrotic cell death, type III-secreted proteins from B. bronchiseptica were analyzed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and electrospray ionization tandem mass spectrometry. We identified a 69-kDa secreted protein designated BopC. The gene encoding BopC is located outside of the TTSS locus and is also highly conserved in both Bordetella parapertussis and Bordetella pertussis. The results of a lactate dehydrogenase release assay and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling assay demonstrated that BopC is required for necrotic cell death. It has been reported that tyrosine-phosphorylated proteins (PY) of host cells are dephosphorylated during B. bronchiseptica infection in a TTSS-dependent manner. We found that BopC is also involved in PY dephosphorylation in infected host cells. It appears that the necrotic cell death triggered by BopC occurs prior to the PY reduction in host cells, because Bordetella-induced cell death was not affected even in the presence of a dephosphorylation inhibitor. Furthermore, a translocation assay showed that the signal sequence for both secretion into culture supernatant and translocation into the host cell is located in 48 amino acid residues of the BopC N terminus. This report reveals for the first time that a novel type III effector, BopC, is required for the induction of necrotic cell death during Bordetella infection.

Constitutive expression of bvgR-repressed factors is not detrimental to the Bordetella bronchiseptica–host interaction

Bordetella bronchiseptica infection requires the activation of virulence genes by the two-component BvgAS regulatory system, which also activates bvgR, a repressor of another set of genes called avirulence genes. Whether or not BvgR-repressed genes play a role in pathogenesis is poorly understood. To evaluate their possible contribution to the bacteria–host interaction we constructed a B. bronchiseptica bvgR insertional mutant ( BbBvgR mutant). As expected, this mutant simultaneously expressed virulence and avirulence markers. In vitro experiments demonstrated that, although the BbBvgR mutant expressed avirulence factors during its virulent state, the bacteria adhered to and survived within human epithelial cells as efficiently as the wild-type strain. The mutant was not impaired for colonization of the respiratory tract in vivo, as it was effectively cleared from lungs during the same time period as the wild-type strain.