Bordetella bronchiseptica pneumonia in a patient with lung cancer; a case report of a rare infection.

BACKGROUND: Bordetella bronchiseptica (B.bronchiseptica) is a frequent cause of respiratory infections in animals but rarely causes serious infection in humans. We present a rare case of B. bronchiseptica pneumonia in a patient with lung cancer. CASE PRESENTATION: A 52-year-old white male with non small cell lung cancer developed fever during treatment with nivolumab. A persistent productive cough and a deterioration in his clinical condition led to his hospitalization for evaluation. Bronchoscopy was performed and a diagnosis of B. bronchiseptica pneumonia was made. The infection was successfully managed by antiobiotic therapy. CONCLUSIONS: B. bronchiseptica is a pathogen that can cause serious infection in humans, especially in immunocompromised or immunoincompetent individuals. In our patient it showed unusual resistance to cephalosporins and poor sensitivity to amikacin. To our knowledge this is the first case of such an infection in a lung cancer patient undergoing treatment with nivolumab. When B. bronchiseptica is identified, the possibility of a nosocomial transmission must be considered.

Bacteriemia recurrente por Bordetella bronchiseptica en un paciente con trasplante de medula ósea / Bordetella bronchiseptica recurrent bacteraemia in a patient with bone marrow transplantation

Se reporta un caso de bacteriemia recurrente por Bordetella bronchiseptica en un paciente inmunocomprometido con antecedentes de trasplante alogénico de medula ósea por síndrome mielodisplásico, quien ingresó al hospital por síndrome febril. Bordetella bronchiseptica es un agente patógeno veterinario poco común en humanos que afecta principalmente a pacientes inmunocomprometidos y es causa poco frecuente de bacteriemia.

We report a case of recurrent bacteraemia caused by Bordetella bronchiseptica in an immunocompromised patient with a history of allogenic bone marrow transplantation for myelodysplastic syndrome, who was admitted to hospital with febrile syndrome. Bordetella bronchiseptica is an uncommon human pathogen which mainly affects immunocompromised patients, being a rare cause of bacteraemia.

[Bordetella bronchiseptica recurrent bacteraemia in a patient with bone marrow transplantation]. / Bacteriemia recurrente por Bordetella bronchiseptica en un paciente con trasplante de medula ósea.

We report a case of recurrent bacteraemia caused by Bordetella bronchiseptica in an immunocompromised patient with a history of allogenic bone marrow transplantation for myelodysplastic syndrome, who was admitted to hospital with febrile syndrome. Bordetella bronchiseptica is an uncommon human pathogen which mainly affects immunocompromised patients, being a rare cause of bacteraemia.

[Bordetella holmesii bacteremia in a 26-year-old patient with sickle cell disease]. / Bactériémie à Bordetella holmesii chez un patient drépanocytaire de 26 ans.

Bordetella holmesii is a rare cause of bacteremia. It occurs mainly in hyposplenic patients, such as those affected by sickle cell anemia. The most frequent clinical signs are not very specific: fever, cephalalgia, cough, dyspnea, vomiting, etc. B. holmesii is frequently isolated from blood cultures. We describe the case of a 26-year-old sickle cell patient, presenting with dry cough and fever caused by a B. holmesii blood stream infection, identified by 16S rRNA gene sequencing. The outcome was favorable with amoxicillin. It is useful to know about B. holmesii, especially for physicians managing sickle cell or hyposplenic patients, because of its variable susceptibility to beta-lactams.

Chronic cholangitis caused by Bordetella hinzii in a liver transplant recipient.

Bordetella hinzii was isolated in four biliary specimens collected over 6 months from a liver transplant recipient with cholangitis. The isolates were resistant to most beta-lactam antibiotics and fluoroquinolones. Molecular typing was performed by pulsed-field gel electrophoresis. These data add cholangitis to the spectrum of disease manifestations caused by B. hinzii.

BhuR, a virulence-associated outer membrane protein of Bordetella avium, is required for the acquisition of iron from heme and hemoproteins.

Iron (Fe) is an essential element for most organisms which must be obtained from the local environment. In the case of pathogenic bacteria, this fundamental element must be acquired from the fluids and tissues of the infected host. A variety of systems have evolved in bacteria for efficient acquisition of host-bound Fe. The gram-negative bacterium Bordetella avium, upon colonization of the avian upper respiratory tract, produces a disease in birds that has striking similarity to whooping cough, a disease caused by the obligate human pathogen Bordetella pertussis. We describe a B. avium Fe utilization locus comprised of bhuR and six accessory genes (rhuIR and bhuSTUV). Genetic manipulations of B. avium confirmed that bhuR, which encodes a putative outer membrane heme receptor, mediates efficient acquisition of Fe from hemin and hemoproteins (hemoglobin, myoglobin, and catalase). BhuR contains motifs which are common to bacterial heme receptors, including a consensus FRAP domain, an NPNL domain, and two TonB boxes. An N-terminal 32-amino-acid segment, putatively required for rhuIR-dependent regulated expression of bhuR, is present in BhuR but not in other bacterial heme receptors. Two forms of BhuR were observed in the outer membrane of B. avium: a 91-kDa polypeptide consistent in size with the predicted mature protein and a smaller 82-kDa polypeptide which lacks the 104 amino acids found at the N terminus of the 91-kDa form. A mutation in hemA was engineered in B. avium to demonstrate that the bacterium transports heme into the cytoplasm in a BhuR-dependent manner. The role of BhuR in virulence was established in turkey poults by use of a competitive-infection model.

Bordetella holmesii bacteraemia in an individual on haemodialysis.

A case of haemodialysis-associated bacteraemia due to Bordetella holmesii is described. Commercially available identification kits failed to identify the isolate, which was speciated using 16s rRNA gene sequencing. B. holmesii is a rare cause of bacteraemia, endocarditis and pneumonia in the immunosuppressed and may also cause a pertussis-like illness.

Effects of long-term induced ostial obstruction in the rabbit maxillary sinus.

One of the widely proposed theories for mucocele formation is sinus ostial obstruction. Accordingly, this study was undertaken to investigate the long-term effects of ostial obstruction in the rabbit maxillary sinus and its potential role in the pathogenesis of mucoceles. Maxillary sinus ostial obstruction was induced on one side in eight Pasteurella-free White New Zealand rabbits using Histoacryl. The rabbits were housed in a Pasteurella-free zone for 24 weeks. At re-exploration, only three of the eight maxillary sinuses where ostial obstruction was induced showed pressure recording consistent with ostial obstruction. Mucociliary clearance activity was assessed using India ink. Swabs for culture were taken from the infected maxillary sinuses. Mucosal specimens for histopathological examination were harvested from one of the maxillary sinuses with obstructed ostium as well as from another sinus with nonobstructed ostium. The three maxillary sinuses with obstructed ostia showed gross evidence of infection and deranged mucociliary clearance, but no mucocele formation. Based on the findings of this study it is concluded that long-term ostial obstruction indeed plays a role in the pathogenesis of chronic sinusitis, but it did not induce mucocele formation in the rabbit maxillary sinus.

Reduced virulence of a Bordetella bronchiseptica siderophore mutant in neonatal swine.

One means by which Bordetella bronchiseptica scavenges iron is through production of the siderophore alcaligin. A nonrevertible alcaligin mutant derived from the virulent strain 4609, designated DBB25, was constructed by insertion of a kanamycin resistance gene into alcA, one of the genes essential for alcaligin biosynthesis. The virulence of the alcA mutant in colostrum-deprived, caesarean-delivered piglets was compared with that of the parent strain in two experiments. At 1 week of age, piglets were inoculated with phosphate-buffered saline, 4609, or DBB25. Two piglets in each group were euthanatized on day 10 postinfection. The remainder were euthanatized at 21 days postinfection. Clinical signs, including fever, coughing, and sneezing, were present in both groups. Nasal washes performed 7, 14, and 21 days postinoculation demonstrated that strain DBB25 colonized the nasal cavity but did so at levels that were significantly less than those achieved by strain 4609. Analysis of colonization based on the number of CFU per gram of tissue recovered from the turbinate, trachea, and lung also demonstrated significant differences between DBB25 and 4609, at both day 10 and day 21 postinfection. Mild to moderate turbinate atrophy was apparent in pigs inoculated with strain 4609, while turbinates of those infected with strain DBB25 developed no or mild atrophy. We conclude from these results that siderophore production by B. bronchiseptica is not essential for colonization of swine but is required for maximal virulence. B. bronchiseptica mutants with nonrevertible defects in genes required for alcaligin synthesis may be candidates for evaluation as attenuated, live vaccine strains in conventionally reared pigs.

Multiple roles for Bordetella lipopolysaccharide molecules during respiratory tract infection.

Bordetella pertussis, Bordetella parapertussis, and Bordetella bronchiseptica are closely related subspecies that cause respiratory tract infections in humans and other mammals and express many similar virulence factors. Their lipopolysaccharide (LPS) molecules differ, containing either a complex trisaccharide (B. pertussis), a trisaccharide plus an O-antigen-like repeat (B. bronchiseptica), or an altered trisaccharide plus an O-antigen-like repeat (B. parapertussis). Deletion of the wlb locus results in the loss of membrane-distal polysaccharide domains in the three subspecies of bordetellae, leaving LPS molecules consisting of lipid A and core oligosaccharide. We have used wlb deletion (Deltawlb) mutants to investigate the roles of distal LPS structures in respiratory tract infection by bordetellae. Each mutant was defective compared to its parent strain in colonization of the respiratory tracts of BALB/c mice, but the location in the respiratory tract and the time point at which defects were observed differed significantly. Although the Deltawlb mutants were much more sensitive to complement-mediated killing in vitro, they displayed similar defects in respiratory tract colonization in C5(-/-) mice compared with wild-type (wt) mice, indicating that increased sensitivity to complement-mediated lysis is not sufficient to explain the in vivo defects. B. pertussis and B. parapertussis Deltawlb mutants were also defective compared to wt strains in colonization of SCID-beige mice, indicating that the defects were not limited to interactions with adaptive immunity. Interestingly, the B. bronchiseptica Deltawlb strain was defective, compared to the wt strain, in colonization of the respiratory tracts of BALB/c mice beginning 1 week postinoculation but did not differ from the wt strain in its ability to colonize the respiratory tracts of B-cell- and T-cell-deficient mice, suggesting that wlb-dependent LPS modifications in B. bronchiseptica modulate interactions with adaptive immunity. These data show that biosynthesis of a full-length LPS molecule by these three bordetellae is essential for the expression of full virulence for mice. In addition, the data indicate that the different distal structures modifying the LPS molecules on these three closely related subspecies serve different purposes in respiratory tract infection, highlighting the diversity of functions attributable to LPS of gram-negative bacteria.

A porcine model for the evaluation of virulence of Bordetella bronchiseptica.

Studies of virulence factors of Bordetella bronchiseptica require a suitable system. Such a system was devised in colostrum-deprived, caesarean-derived pigs, aged 7 d. In two different experiments, pigs (n = 11) were inoculated intranasally with 10(6) colony-forming units of the virulent strain 4609. In the same way, further pigs (n = 11) were inoculated with a strain (B133) of unknown virulence. No significant differences between 4609 and B133 colonization were seen. However, colonization of the turbinates was significantly higher than that of the trachea, lung and tonsil, and a significantly higher degree of colonization was present at 11 d post-inoculation (PI) than at 15 days. Moderate turbinate atrophy was present by 11 d PI, and peribronchiolar fibrosis was present at 15 days. Immunocytochemical methods showed that all pigs had bacterial antigen in the ciliated cells of the turbinates and trachea, and in the lung; some pigs also had antigen in the bronchi. Bacterial antigen was present in some bronchioles and within the cytoplasm of pulmonary macrophages and neutrophils. This model should prove useful for comparing strains of B. bronchiseptica and isogenic mutants deficient in putative virulence factors.

Crystal containing membrane bound intracellular inclusion bodies in the epithelium of experimentally infected sinus mucosa.

The sinus mucosa of 16 rabbits was experimentally infected with Bacteroides fragilis. This paper describes and discusses large inclusion bodies, which were found in abundance by light and electron microscopy inside ciliated cells of the sinus epithelium in 3 of the studied animals. The spindle-shaped inclusions were located in the apical portion of the cytoplasm. They were bound by a trilaminar membrane with several coils to the interior as well as to the exterior. The interior of an inclusion body consisted to a large extent of electron-lucent, floccular substance, but fibrogranular aggregates and rod-shaped crystals with a line periodicity center-to-center of about 15 nm were also conspicuous. These peculiar formations may be constituted by abnormally stored material from defective synthesis of cilia.

Bordetella bronchoseptica pneumonia with shock in an immunocompetent patient.

Bordetella bronchoseptica is a rarely reported cause of human infection, but is a common respiratory tract commensal of mammals. Human infection with B. bronchoseptica is almost always associated with severe underlying disease and contact with an appropriate animal reservoir. We report a case of pneumonia with shock caused by B. bronchoseptica in an immunocompetent patient.

Human Bordetella bronchiseptica infection related to contact with infected animals: persistence of bacteria in host.

Within a period of 2 1/2 years, Bordetella bronchiseptica was isolated four times from a 79-year-old woman with bronchopneumonia. We have demonstrated by pulsed-field gel electrophoresis that this infection was related to contact with infected rabbits. The initial human B. bronchiseptica isolate had a phenotype characteristic of usual B. bronchiseptica clinical isolates; it produced toxin and adhesins, such as adenylate cyclase-hemolysin, filamentous hemagglutinin, and pertactin, and was able to induce lethality in a murine respiratory model. By contrast, although the three successive human isolates produced adhesins, they did not express adenylate cyclase-hemolysin and were unable to induce lethality. This implies that adenylate cyclase-hemolysin is required to induce lethality. We suggest that B. bronchiseptica may persist in the host, with expression of adenylate cyclase-hemolysin being essential for the initiation of infection and expression of adhesins being essential for persistence.

BvgAS-mediated signal transduction: analysis of phase-locked regulatory mutants of Bordetella bronchiseptica in a rabbit model.

Members of the Bordetella genus alternate between two distinct phenotypic phases in response to changes in their environment. This switch, termed phenotypic modulation, is mediated by the BvgAS sensory transduction system. We developed an animal model based on the interaction of Bordetella bronchiseptica with one of its natural hosts, the rabbit. To investigate the importance of BvgAS signal transduction, we constructed constitutive (RB53) and Bvg- (RB54) phase-locked derivatives of a wild-type strain, RB50. RB50 and RB53, but not RB54, established respiratory infections in B. bronchiseptica-free rabbits with an intranasal 50% infective dose of less than 200 organisms, and the course of the infection closely resembled that observed with naturally infected rabbits. Bacteria were recovered from the nasal cavity, larynx, trachea, and lungs in similar numbers from RB50- and RB53-infected rabbits, yet no pathology was detected by histological examination of lung and tracheal sections. The antibody responses in rabbits inoculated with RB50 or RB53 were quantitatively and qualitatively indistinguishable; high titers of antibodies were generated primarily against Bvg(+)-phase-specific antigens. No response against flagella, a Bvg- phase factor, was detected. Assessment of bacteria associated with alveolar macrophages indicated that only a small percentage of bacteria, if any, appear to be residing within lung macrophages. We also tested the ability of these strains to survive in a nutrient poor environment, conditions which may be encountered within certain niches in the host or in an environmental reservoir. The Bvg- phase was advantageous for growth under these conditions. Our results indicate the Bvg+ phase is sufficient for establishment of respiratory tract infection in the rabbit and the normal BvgAS-mediated response to environmental signals is not required during initial colonization. The Bvg- phase may play a role at later stages of infection, including persistence, transmission, or survival in the environment.

Fimbriae and determination of host species specificity of Bordetella bronchiseptica.

A monoclonal antibody, designated CF8 and prepared against fimbrial protein enrichments of Bordetella bronchiseptica 110H, was determined by immunogold electron microscopy to bind to some but not all fimbrial filaments on intact bacterial cells. Comparison of the reactivity of this antibody with that of monoclonal antibody BPF2, which is specific for Bordetella pertussis serotype 2 fimbriae, indicated that CF8 recognizes an epitope similar to that recognized by BPF2. By Western blot (immunoblot), it was determined that monoclonal antibody CF8 does not react with proteins denatured by treatment with sodium dodecyl sulfate and beta-mercaptoethanol and by boiling for 5 min but that it does recognize fimbrial proteins in their native, nondenatured state. This antibody was used to compare fimbriae between strains of B. bronchiseptica isolated from different species. Strains from pigs, dogs, guinea pigs, and four other species were compared by an enzyme immunoassay. Strains isolated from pigs were found to express significantly more CF8-reactive and B. pertussis serotype 2 cross-reactive fimbriae than strains isolated from guinea pigs. Strains from dogs were more variable in reactivity than those from pigs or guinea pigs. The reactivity with antifimbrial monoclonal antibody CF8 did not correlate with enzyme electromorphotype but did correlate with the host species, suggesting a role for fimbriae in the determination of host species specificity of B. bronchiseptica.