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1.
Int J Mol Sci ; 25(9)2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38731927

RESUMO

Bordetella hinzii (B. hinzii), a Gram-negative bacillus commonly associated with respiratory infections in animals, has garnered attention for its sporadic cases in humans, particularly in immunocompromised individuals. Despite its opportunistic nature, there remains limited understanding regarding its pathogenicity, diagnostic challenges, and optimal treatment strategies, especially in the context of immunosuppression. Herein, we present the first documented case of acute bronchitis caused by B. hinzii in an immunocompromised patient following double-lung transplantation. The patient, a former smoker with sarcoidosis stage IV, underwent transplant surgery and subsequently developed a febrile episode, leading to the identification of B. hinzii in broncho-alveolar lavage samples. Antimicrobial susceptibility testing revealed resistance to multiple antibiotics, necessitating tailored treatment adjustments. Our case underscores the importance of heightened awareness among clinicians regarding B. hinzii infections and the imperative for further research to elucidate its epidemiology and optimal management strategies, particularly in immunocompromised populations.


Assuntos
Infecções por Bordetella , Bordetella , Hospedeiro Imunocomprometido , Transplante de Pulmão , Transplante de Pulmão/efeitos adversos , Humanos , Bordetella/isolamento & purificação , Infecções por Bordetella/microbiologia , Infecções por Bordetella/diagnóstico , Masculino , Pessoa de Meia-Idade , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Transplantados
2.
J Int Med Res ; 52(1): 3000605231214464, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38216150

RESUMO

An increasing number of reports have described the pathogenic nature of several non-classical Bordetella spp. Among them, Bordetella hinzii and Bordetella pseudohinzii have been implicated in a myriad of respiratory-associated infections in humans and animals. We report the isolation of a genetically close relative of B. hinzii and B. pseudohinzii from the sputum of a woman in her early 60s with extensive bronchiectasis who presented with fever and brown colored sputum. The isolate had initially been identified as Bordetella avium by API 20NE, the identification system for non-enteric Gram-negative rod bacteria. Sequencing of the 16S rDNA, ompA, nrdA, and genes used in the Bordetella multilocus sequence typing scheme could not resolve the identity of this Bordetella isolate. Whole-genome single nucleotide polymorphism analysis positioned the isolate between B. hinzii and B. pseudohinzii in the phylogenetic tree, forming a distinct cluster. Whole-genome sequencing enabled the further identification of this rare organism, and should be considered for wider applications, especially the confirmation of organism identity in the clinical diagnostic microbiology laboratory.


Assuntos
Infecções por Bordetella , Bordetella , Bronquiectasia , Infecções Respiratórias , Humanos , Animais , Feminino , Infecções por Bordetella/diagnóstico , Infecções por Bordetella/microbiologia , Filogenia , Bordetella/genética , Bronquiectasia/complicações , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/microbiologia
3.
Front Cell Infect Microbiol ; 13: 1111502, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37065208

RESUMO

Introduction: Bordetella are respiratory pathogens comprised of three classical Bordetella species: B. pertussis, B. parapertussis, and B. bronchiseptica. With recent surges in Bordetella spp. cases and antibiotics becoming less effective to combat infectious diseases, there is an imperative need for novel antimicrobial therapies. Our goal is to investigate the possible targets of host immunomodulatory mechanisms that can be exploited to promote clearance of Bordetella spp. infections. Vasoactive intestinal peptide (VIP) is a neuropeptide that promotes Th2 anti-inflammatory responses through VPAC1 and VPAC2 receptor binding and activation of downstream signaling cascades. Methods: We used classical growth in vitro assays to evaluate the effects of VIP on Bordetella spp. growth and survival. Using the three classical Bordetella spp. in combination with different mouse strains we were able to evaluate the role of VIP/VPAC2 signaling in the infectious dose 50 and infection dynamics. Finally using the B. bronchiseptica murine model we determine the suitability of VPAC2 antagonists as possible therapy for Bordetella spp. infections. Results: Under the hypothesis that inhibition of VIP/VPAC2 signaling would promote clearance, we found that VPAC2-/- mice, lacking a functional VIP/VPAC2 axis, hinder the ability of the bacteria to colonize the lungs, resulting in decreased bacterial burden by all three classical Bordetella species. Moreover, treatment with VPAC2 antagonists decrease lung pathology, suggesting its potential use to prevent lung damage and dysfunction caused by infection. Our results indicate that the ability of Bordetella spp. to manipulate VIP/VPAC signaling pathway appears to be mediated by the type 3 secretion system (T3SS), suggesting that this might serve as a therapeutical target for other gram-negative bacteria. Conclusion: Taken together, our findings uncover a novel mechanism of bacteria-host crosstalk that could provide a target for the future treatment for whooping cough as well as other infectious diseases caused primarily by persistent mucosal infections.


Assuntos
Infecções por Bordetella , Peptídeo Intestinal Vasoativo , Animais , Camundongos , Infecções por Bordetella/microbiologia , Bordetella pertussis , Pulmão/microbiologia , Receptores Tipo II de Peptídeo Intestinal Vasoativo/metabolismo , Transdução de Sinais , Sistemas de Secreção Tipo III , Peptídeo Intestinal Vasoativo/metabolismo
4.
Sci Rep ; 11(1): 17535, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34475490

RESUMO

Cystic fibrosis (CF) is an autosomal recessive disease caused by dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR) protein, and is marked by an accumulation of mucus in affected airways resulting in persistent infection and chronic inflammation. Quantitative differences in inflammatory markers have been observed in CF patient serum, tracheal cells, and bronchoalveolar lavage fluid, in the absence of detectable infection, implying that absent CFTR function alone may result in dysregulated immune responses. To examine the relationship between absent CFTR and systemic inflammation, 22 analytes were measured in CF mice (F508del/F508del) sera using the MSD multiplex platform. Pro-inflammatory cytokines IL-2, TNF-α, IL-17α, IFN-γ, IL-1ß, and MIP-3α are significantly elevated in infection-naïve CF mice (p < 0.050). Anti-inflammatory cytokines IL-10 and IL-4 are also significantly increased (p = 0.00003, p = 0.004). Additionally, six general markers of inflammation are significantly different from non-CF controls (p < 0.050). To elucidate the effects of chronic infection on the CF inflammatory profile, we examined CF mice exposed to spontaneous Bordetella pseudohinzii infections. There are no statistical differences in nearly all inflammatory markers when compared to their infection-naïve CF counterparts, except in the Th2-derived IL-4 and IL-5 which demonstrate significant decreases following exposure (p = 0.046, p = 0.045). Lastly, following acute infection, CF mice demonstrate elevations in nearly all inflammatory markers, but exhibit a shortened return to uninfected levels over time, and suppression of Th1-derived IL-2 and IL-5 (p = 0.043, p = 0.011). These results imply that CF mice have a persistent inflammatory profile often indistinguishable from chronic infection, and a dysregulated humoral response during and following active infection.


Assuntos
Infecções por Bordetella/complicações , Bordetella/isolamento & purificação , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Fibrose Cística/microbiologia , Citocinas/sangue , Inflamação/diagnóstico , Mutação , Animais , Infecções por Bordetella/metabolismo , Infecções por Bordetella/microbiologia , Fibrose Cística/genética , Fibrose Cística/patologia , Modelos Animais de Doenças , Feminino , Inflamação/sangue , Inflamação/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL
5.
BMC Infect Dis ; 20(1): 922, 2020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33272197

RESUMO

BACKGROUND: Bordetella bronchiseptica is a gram-negative, obligate aerobic coccobacillus known to cause disease in domesticated animals and pets. In humans, B. bronchiseptica commonly leads to respiratory infections like pneumonia or bronchitis, and animal contact usually precedes the onset of symptoms. CASE PRESENTATION: We report a case of post-traumatic B. bronchiseptica meningitis without recent surgery in the setting of immunosuppression with a monoclonal antibody. Our case concerns a 77-year-old male with ulcerative colitis on infliximab who sustained a mechanical fall and developed a traumatic cerebrospinal fluid leak complicated by meningitis. He received meropenem then ceftazidime during his hospital course, and temporary neurosurgical drain placement was required. His clinical condition improved, and he was discharged at his baseline neurological status. CONCLUSIONS: B. bronchiseptica is an unusual cause of meningitis that may warrant consideration in immunocompromised hosts with known or suspected animal exposures. To better characterize this rare cause of meningitis, we performed a systematic literature review and summarized all previously reported cases.


Assuntos
Antibacterianos/uso terapêutico , Infecções por Bordetella/tratamento farmacológico , Bordetella bronchiseptica/isolamento & purificação , Ceftazidima/uso terapêutico , Meningite/tratamento farmacológico , Meningite/cirurgia , Meropeném/uso terapêutico , Idoso , Animais , Infecções por Bordetella/microbiologia , Vazamento de Líquido Cefalorraquidiano/complicações , Colite Ulcerativa/tratamento farmacológico , Drenagem/métodos , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/uso terapêutico , Infliximab/uso terapêutico , Masculino , Meningite/etiologia , Meningite/microbiologia , Procedimentos Neurocirúrgicos/métodos , Resultado do Tratamento
6.
Can J Vet Res ; 84(3): 181-188, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32801452

RESUMO

The prevalence of the causative agents of feline upper respiratory tract disease (URTD) has been previously documented in many regions worldwide, but has yet to be reported in eastern Canada. The objectives of this study were to determine the prevalence of feline herpesvirus-1 (FHV-1), feline calicivirus (FCV), Chlamydia felis (C. felis), and Bordetella bronchiseptica (B. bronchiseptica) in a population of shelter cats with clinical signs related to URTD on Prince Edward Island, Canada; to compare the prevalence of FHV-1 and FCV as detected by polymerase chain reaction (PCR) and virus isolation (VI) in this population; and lastly, to determine whether factors, such as co-infections, time of year, concurrent feline leukemia virus (FeLV)- or feline immunodeficiency virus (FIV)-positive status, or clinical signs, were associated with prevalence of particular pathogens. Conjunctival, nasal mucosal, and oropharyngeal swabs were collected from 82 cats with clinical signs consistent with URTD. Samples were pooled in transport medium and PCR was used to detect FHV-1, FCV, and C. felis and VI was also used to detect FHV-1 and FCV. A separate swab was submitted for aerobic bacterial culture to detect B. bronchiseptica. Feline herpesvirus-1 (FHV-1) was the most prevalent in this population, followed by C. felis, B. bronchiseptica, and FCV. Of the 4 cats that were positive for B. bronchiseptica, 3 were concurrently positive for FHV-1. All positive B. bronchiseptica cultures were resistant to cefovecin. The prevalence for FHV-1 was lowest in autumn (seasons P < 0.001) and was positively associated with the presence of nasal discharge (P = 0.018) and coughing (P = 0.043).


La prévalence des agents causals de maladies du tractus respiratoire supérieur félin (URTD) a été préalablement documentée dans plusieurs régions du monde mais n'a pas encore été rapportée dans l'est du Canada. Les objectifs de la présente étude étaient de déterminer la prévalence d'herpès virus félin-1 (FHV-1), du calicivirus félin (FCV), de Chlamydia felis et de Bordetella bronchiseptica dans une population de chats de refuge de l'Île-du-Prince-Édouard, Canada avec des signes cliniques reliés au URTD; de comparer la prévalence de FHV-1 et FCV telle que détecter par réaction d'amplification en chaîne par la polymérase (PCR) et l'isolement viral (VI) dans ces populations; et finalement, déterminer si des facteurs, tels que les co-infections, la période de l'année, le statut concomitant positif pour le virus de la leucémie féline (FeLV) ou le virus de l'immunodéficience féline (FIV) ou les signes cliniques étaient associés avec la prévalence d'un agent pathogène en particulier. Des écouvillons de la conjonctive, de la muqueuse nasale et de l'oropharynx furent obtenus de 82 chats avec des signes cliniques compatibles avec URTD. Les échantillons étaient regroupés dans un milieu de transport et la PCR utilisée pour détecter FHV-1, FCV et C. felis et l'isolement viral fut également utilisé pour détecter FHV-1 et FCV. Un écouvillon séparé fut soumis pour culture bactérienne aérobie afin de détecter B. bronchiseptica. Le FHV-1 était le plus prévalent dans cette population, suivi par C. felis, B. bronchiseptica et FCV. Des quatre chats qui étaient positifs pour B. bronchiseptica, trois étaient positifs également pour FHV-1. Tous les isolats de B. bronchiseptica obtenus étaient résistants au céfovecin. La prévalence de FHV-1 était à son plus bas en automne (P < 0,001 pour les saisons) et était associée positivement avec la présence d'écoulement nasal (P = 0,018) et de la toux (P = 0,043).(Traduit par Docteur Serge Messier).


Assuntos
Infecções por Bordetella/veterinária , Calicivirus Felino , Doenças do Gato/epidemiologia , Infecções por Chlamydia/veterinária , Chlamydia/isolamento & purificação , Herpesviridae/classificação , Animais , Infecções por Bordetella/epidemiologia , Infecções por Bordetella/microbiologia , Bordetella bronchiseptica/isolamento & purificação , Infecções por Caliciviridae/epidemiologia , Infecções por Caliciviridae/veterinária , Doenças do Gato/microbiologia , Doenças do Gato/virologia , Gatos , Infecções por Chlamydia/epidemiologia , Infecções por Chlamydia/microbiologia , Estudos Transversais , Herpesviridae/isolamento & purificação , Abrigo para Animais , Ilha do Príncipe Eduardo/epidemiologia
7.
J Feline Med Surg ; 22(6): 492-499, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31246133

RESUMO

OBJECTIVES: The aim of this study was to assess the effects of famciclovir administration in cats with spontaneously acquired acute upper respiratory tract disease. METHODS: Twenty-four kittens with clinical signs of acute upper respiratory tract disease were randomly allocated to receive doxycycline (5 mg/kg PO q12h) alone (group D; n = 12) or with famciclovir (90 mg/kg PO q12h; group DF; n = 12) for up to 3 weeks. Clinical disease severity was scored at study entry and daily thereafter. Oculo-oropharyngeal swabs collected at study entry and exit were assessed using quantitative PCR for nucleic acids of feline herpesvirus type 1 (FHV-1), feline calicivirus (FCV), Chlamydia felis, Bordetella bronchiseptica and Mycoplasma felis. RESULTS: The median (range) age of cats was 1.5 (1-6) months in group D vs 1.6 (1-5) months in group DF (P = 0.54). Pathogens detected in oculo-oropharyngeal swabs at study entry included FCV (n = 13/24; 54%), M felis (n = 8/24; 33%), FHV-1 (n = 7/24; 29%), C felis (n = 7/24; 29%) and B bronchiseptica (n = 3/24; 12%). Median (range) duration of clinical signs was 11.5 (3-21) days in group DF and 11 (3-21) days in group D (P = 0.75). Median (range) total disease score at the end of the study did not differ between groups (group D 1 [1-1] vs group DF 1 [1-3]; P = 0.08). CONCLUSIONS AND RELEVANCE: This study revealed no significant difference in response to therapy between cats treated with doxycycline alone or with famciclovir; cats improved rapidly in both groups. However, identification of FHV-1 DNA was relatively uncommon in this study and clinical trials focused on FHV-1-infected cats are warranted to better evaluate famciclovir efficacy.


Assuntos
Antivirais/administração & dosagem , Doenças do Gato/tratamento farmacológico , Famciclovir/administração & dosagem , Infecções Respiratórias/veterinária , Animais , Infecções por Bordetella/tratamento farmacológico , Infecções por Bordetella/microbiologia , Infecções por Bordetella/veterinária , Bordetella bronchiseptica/isolamento & purificação , Bordetella bronchiseptica/fisiologia , Infecções por Caliciviridae/tratamento farmacológico , Infecções por Caliciviridae/veterinária , Infecções por Caliciviridae/virologia , Calicivirus Felino/isolamento & purificação , Calicivirus Felino/fisiologia , Doenças do Gato/microbiologia , Doenças do Gato/virologia , Gatos , Chlamydia/isolamento & purificação , Chlamydia/fisiologia , Infecções por Chlamydia/tratamento farmacológico , Infecções por Chlamydia/microbiologia , Infecções por Chlamydia/veterinária , Infecções por Herpesviridae/tratamento farmacológico , Infecções por Herpesviridae/veterinária , Infecções por Herpesviridae/virologia , Mycoplasma/isolamento & purificação , Mycoplasma/fisiologia , Infecções por Mycoplasma/tratamento farmacológico , Infecções por Mycoplasma/microbiologia , Infecções por Mycoplasma/veterinária , Ácidos Nucleicos/análise , Reação em Cadeia da Polimerase em Tempo Real/veterinária , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/microbiologia , Infecções Respiratórias/virologia , Varicellovirus/isolamento & purificação , Varicellovirus/fisiologia
8.
Can J Cardiol ; 35(11): 1604.e17-1604.e19, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31679629

RESUMO

Bordetella hinzii's route of transmission to human hosts and its pathogenicity remain unclear. Only a few cases have established this species as an opportunistic zoonotic disease. We introduce the first reported case of native aortic valve endocarditis presenting with fulminant aortic valve insufficiency that responded to conventional medical and surgical treatment. The patient did not have predisposing factors to this unusual infection. This case may provide a better understanding of the disease process, transmission, and pathogenicity of Bordetella hinzii.


Assuntos
Insuficiência da Valva Aórtica/etiologia , Valva Aórtica/microbiologia , Infecções por Bordetella/microbiologia , Bordetella/isolamento & purificação , Endocardite Bacteriana/microbiologia , Valva Aórtica/diagnóstico por imagem , Insuficiência da Valva Aórtica/diagnóstico , Insuficiência da Valva Aórtica/microbiologia , Biópsia , Infecções por Bordetella/complicações , Infecções por Bordetella/diagnóstico , Ecocardiografia Doppler , Endocardite Bacteriana/complicações , Endocardite Bacteriana/diagnóstico , Feminino , Humanos , Pessoa de Meia-Idade
9.
BMC Infect Dis ; 19(1): 485, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31146691

RESUMO

BACKGROUND: Bordetella trematum is an infrequent Gram-negative coccobacillus, with a reservoir, pathogenesis, a life cycle and a virulence level which has been poorly elucidated and understood. Related information is scarce due to the low frequency of isolates, so it is important to add data to the literature about this microorganism. CASE PRESENTATION: We report a case of a 74-year-old female, who was referred to the hospital, presenting with ulcer and necrosis in both legs. Therapy with piperacillin-tazobactam was started and peripheral artery revascularization was performed. During the surgery, a tissue fragment was collected, where Bordetella trematum, Stenotrophomonas maltophilia, and Enterococcus faecalis were isolated. After surgery, the intubated patient was transferred to the intensive care unit (ICU), using vasoactive drugs through a central venous catheter. Piperacillin-tazobactam was replaced by meropenem, with vancomycin prescribed for 14 days. Four days later, levofloxacin was added for 24 days, aiming at the isolation of S. maltophilia from the ulcer tissue. The necrotic ulcers evolved without further complications, and the patient's clinical condition improved, leading to temporary withdrawal of vasoactive drugs and extubation. Ultimately, however, the patient's general condition worsened, and she died 58 days after hospital admission. CONCLUSIONS: Despite being a rare finding, B. trematum is typically associated with the clinical manifestation of disorders that predispose to ulcer development, which can be infected by microorganisms. The combination of antibiotic therapy and surgical debridement plays a key role in preventing systemic infections. Monitoring the appearance of new cases of B. trematum is essential, since it can be an emerging microorganism. Isolating and defining the clinical relevance of unusual bacteria yields a more accurate perspective in the development of new diagnostic tools and allows for assessment of proper antimicrobial therapy.


Assuntos
Infecções por Bordetella/diagnóstico , Bordetella , Idoso , Antibacterianos/uso terapêutico , Bordetella/isolamento & purificação , Infecções por Bordetella/tratamento farmacológico , Infecções por Bordetella/microbiologia , Coinfecção , Pé Diabético/complicações , Pé Diabético/diagnóstico , Pé Diabético/tratamento farmacológico , Pé Diabético/microbiologia , Enterococcus faecalis/isolamento & purificação , Evolução Fatal , Feminino , Infecções por Bactérias Gram-Negativas/complicações , Infecções por Bactérias Gram-Negativas/diagnóstico , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/microbiologia , Infecções por Bactérias Gram-Positivas/complicações , Infecções por Bactérias Gram-Positivas/diagnóstico , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/microbiologia , Humanos , Unidades de Terapia Intensiva , Testes de Sensibilidade Microbiana , Necrose/diagnóstico , Necrose/microbiologia , Combinação Piperacilina e Tazobactam/uso terapêutico , Stenotrophomonas maltophilia/isolamento & purificação , Úlcera/diagnóstico , Úlcera/microbiologia
10.
J Infect ; 78(1): 48-53, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30048653

RESUMO

OBJECTIVE: To investigate the clinical manifestations, microbiological data, and outcomes of Bordetella bronchiseptica (Bb) infections in patients with cancer. METHODS: Review of electronic medical records of 24 patients with Bb infection, from 2000 to 2013. An infection was considered to be associated with Bb if both clinical manifestations plus microbial growth from infected sites were present. RESULTS: Ten patients (42%) had a monomicrobial infection, whereas multiple pathogens in addition to Bb were isolated from the rest (14 patients, 58%). The most frequent sites of infection were the respiratory tract (18 patients, 75 %) and bloodstream (17%). The most frequently associated conditions were lymphopenia (71%), tobacco use (42%), and chemotherapeutic or immunosuppressive agents (33% each). Animal exposure was established in four patients. Overall, the response rate to treatment was 100% for monomicrobial and 79% for polymicrobial infections, respectively. CONCLUSIONS: Bb is an uncommon pathogen even in immunosuppressed patients. Predominant sites of infection are the respiratory tract and bloodstream. Bb should be considered pathogenic in immunocompromised hosts, particularly with history of zoonotic exposure, even if accompanied by co-pathogens. Therefore, contact with potential animal sources should be minimized. The infection ranges from mild to severe and has no specific clinical or radiographic manifestations.


Assuntos
Tosse/microbiologia , Hospedeiro Imunocomprometido , Neoplasias/complicações , Infecções Respiratórias/microbiologia , Adulto , Idoso , Infecções por Bordetella/microbiologia , Bordetella bronchiseptica/isolamento & purificação , Bordetella bronchiseptica/patogenicidade , Coinfecção , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
11.
Appl Environ Microbiol ; 84(4)2018 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-29180369

RESUMO

Bordetella bronchiseptica, a Gram-negative bacterium, causes chronic respiratory tract infections in a wide variety of mammalian hosts, including humans (albeit rarely). We recently designed Bordetella pertussis and Bordetella parapertussis experimental vaccines based on outer membrane vesicles (OMVs) derived from each pathogen, and we obtained protection against the respective infections in mice. Here, we demonstrated that OMVs derived from virulent-phase B. bronchiseptica (OMVBbvir+) protected mice against sublethal infections with different B. bronchiseptica strains, two isolated from farm animals and one isolated from a human patient. In all infections, we observed that the B. bronchiseptica loads were significantly reduced in the lungs of vaccinated animals; the lung-recovered CFU were decreased by ≥4 log units, compared with those detected in the lungs of nonimmunized animals (P < 0.001). In the OMVBbvir+-immunized mice, we detected IgG antibody titers against B. bronchiseptica whole-cell lysates, along with an immune serum having bacterial killing activity that both recognized B. bronchiseptica lipopolysaccharides and polypeptides such as GroEL and outer membrane protein C (OMPc) and demonstrated an essential protective capacity against B. bronchiseptica infection, as detected by passive in vivo transfer experiments. Stimulation of cultured splenocytes from immunized mice with OMVBbvir+ resulted in interleukin 5 (IL-5), gamma interferon (IFN-γ), and IL-17 production, indicating that the vesicles induced mixed Th2, Th1, and Th17 T-cell immune responses. We detected, by adoptive transfer assays, that spleen cells from OMVBbvir+-immunized mice also contributed to the observed protection against B. bronchiseptica infection. OMVs from avirulent-phase B. bronchiseptica and the resulting induced immune sera were also able to protect mice against B. bronchiseptica infection.IMPORTANCEBordetella bronchiseptica, a Gram-negative bacterium, causes chronic respiratory tract infections in a wide variety of mammalian hosts, including humans (albeit rarely). Several vaccines aimed at preventing B. bronchiseptica infection have been developed and used, but a safe effective vaccine is still needed. The significance and relevance of our research lie in the characterization of the OMVs derived from B. bronchiseptica as the source of a new experimental vaccine. We demonstrated here that our formulation based on OMVs derived from virulent-phase B. bronchiseptica (OMVBbvir+) was effective against infections caused by B. bronchiseptica isolates obtained from different hosts (farm animals and a human patient). In vitro and in vivo characterization of humoral and cellular immune responses induced by the OMVBbvir+ vaccine enabled a better understanding of the mechanism of protection necessary to control B. bronchiseptica infection. Here we also demonstrated that OMVs derived from B. bronchiseptica in the avirulent phase and the corresponding induced humoral immune response were able to protect mice from B. bronchiseptica infection. This realization provides the basis for the development of novel vaccines not only against the acute stages of the disease but also against stages of the disease or the infectious cycle in which avirulence factors could play a role.


Assuntos
Proteínas da Membrana Bacteriana Externa/imunologia , Vacinas Bacterianas/imunologia , Infecções por Bordetella/prevenção & controle , Bordetella bronchiseptica/citologia , Bordetella bronchiseptica/patogenicidade , Animais , Anticorpos Antibacterianos/sangue , Vacinas Bacterianas/administração & dosagem , Infecções por Bordetella/imunologia , Infecções por Bordetella/microbiologia , Bordetella bronchiseptica/química , Bordetella bronchiseptica/imunologia , Feminino , Humanos , Imunidade Celular , Imunidade Humoral , Imunização , Camundongos , Camundongos Endogâmicos BALB C , Fenótipo , Infecções Respiratórias/imunologia , Infecções Respiratórias/microbiologia , Infecções Respiratórias/prevenção & controle , Células Th17/imunologia , Virulência
12.
Transpl Infect Dis ; 19(6)2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28865149

RESUMO

Bordetella bronchiseptica is a gram-negative coccobacillus that infects animals, but rarely affects humans. B. bronchiseptica has been reported to cause disease in immunocompromised hosts. We present a case of a 61-year-old man with a renal transplant who developed B. bronchiseptica bacteremia likely as a result of close contact between dogs and his skin cancer biopsy sites. The patient was successfully treated with 2 weeks of oral levofloxacin. This case alerts physicians to B. bronchiseptica as a cause of bacteremia in solid organ transplant patients with exposure to animals.


Assuntos
Antibacterianos/uso terapêutico , Bacteriemia/microbiologia , Infecções por Bordetella/transmissão , Bordetella bronchiseptica/isolamento & purificação , Cães/microbiologia , Transplante de Rim/efeitos adversos , Animais , Bacteriemia/tratamento farmacológico , Biópsia/efeitos adversos , Infecções por Bordetella/sangue , Infecções por Bordetella/tratamento farmacológico , Infecções por Bordetella/microbiologia , Humanos , Hospedeiro Imunocomprometido , Terapia de Imunossupressão/efeitos adversos , Falência Renal Crônica/cirurgia , Levofloxacino/uso terapêutico , Masculino , Pessoa de Meia-Idade , Pele/patologia , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/patologia
13.
Med Mal Infect ; 47(7): 453-458, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28943167

RESUMO

OBJECTIVE: To collect data of all patients admitted to hospital with a positive test to Bordetella bronchiseptica between 2001 and 2015. METHODS: We performed a retrospective monocentric study of all hospitalized patients over the past 15 years with a positive test to B. bronchiseptica. RESULTS: Nine patients were included between 2001 and 2015; two presented with infectious relapses, i.e. a total of 14 positive test samples were observed. Age, induced immunodeficiency, and preexisting respiratory illnesses are risk factors. All patients showed symptoms at sample collection and the infection was exclusively respiratory. The diagnosis was obtained through a cytobacteriological test of sputum, bronchial aspiration, or bronchial fibroscopy with a bronchoalveolar lavage. The drug susceptibility test revealed a natural resistance to cephalosporins including ceftazidime, monobactam, and fosfomycin. There were cases of resistance to penicillin A and to the trimethoprim/sulfamethoxazole association. The classically used antibiotic treatment for community-acquired pneumonia is based on probability and may thus fail. Four patients died. The duration and nature of the antibiotics to use have not been codified. CONCLUSION: B. bronchiseptica infection mainly affects the elderly. All patients should be treated, regardless of the importance of the inoculum, and all infected animals should be treated.


Assuntos
Infecções por Bordetella/epidemiologia , Bordetella/isolamento & purificação , Idoso , Idoso de 80 Anos ou mais , Bordetella/efeitos dos fármacos , Infecções por Bordetella/diagnóstico , Infecções por Bordetella/microbiologia , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/microbiologia , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Suscetibilidade a Doenças , Resistência Microbiana a Medicamentos , Feminino , Humanos , Hospedeiro Imunocomprometido , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Estudos Retrospectivos , Fatores de Risco
14.
Microbiol Immunol ; 61(6): 206-214, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28500733

RESUMO

Bordetella bronchiseptica infects a wide variety of mammals, the type III secretion system (T3SS) being involved in long-term colonization by Bordetella of the trachea and lung. T3SS translocates virulence factors (commonly referred to as effectors) into host cells, leading to alterations in the host's physiological function. The Bordetella effectors BopN and BteA are known to have roles in up-regulation of IL-10 and cytotoxicity, respectively. Nevertheless, the mechanism by which BopN is translocated into host cells has not been examined in sufficient detail. Therefore, to determine the precise mechanisms of translocation of BopN into host cells, truncated derivatives of BopN were built and the derivatives' ability to translocate into host cells evaluated by adenylate cyclase-mediated translocation assay. It was found that N-terminal amino acid (aa) residues 1-200 of BopN are sufficient for its translocation into host cells. Interestingly, BopN translocation was completely blocked by deletion of the N-terminal aa residues 6-50, indicating that the N-terminal region is critical for BopN translocation. Furthermore, BopN appears to play an auxiliary role in BteA-mediated cytotoxicity. Thus, BopN can apparently translocate into host cells and may facilitate activity of BteA.


Assuntos
Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Infecções por Bordetella/microbiologia , Bordetella bronchiseptica/genética , Bordetella bronchiseptica/metabolismo , Transporte Proteico , Adenilil Ciclases , Sequência de Aminoácidos , Animais , Anticorpos Antibacterianos , Proteínas de Bactérias/imunologia , Linhagem Celular , Citotoxicidade Imunológica , DNA Bacteriano , Escherichia coli/genética , Regulação da Expressão Gênica , Genes Bacterianos , Vetores Genéticos , Interações Hospedeiro-Patógeno , Interleucina-10 , Transporte Proteico/fisiologia , Ratos , Deleção de Sequência , Sistemas de Secreção Tipo III/genética , Sistemas de Secreção Tipo III/metabolismo , Regulação para Cima , Fatores de Virulência/metabolismo
15.
PLoS One ; 12(1): e0169936, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28095485

RESUMO

B. parapertussis is a whooping cough etiological agent with the ability to evade the immune response induced by pertussis vaccines. We previously demonstrated that in the absence of opsonic antibodies B. parapertussis hampers phagocytosis by neutrophils and macrophages and, when phagocytosed, blocks intracellular killing by interfering with phagolysosomal fusion. But neutrophils can kill and/or immobilize extracellular bacteria through non-phagocytic mechanisms such as degranulation and neutrophil extracellular traps (NETs). In this study we demonstrated that B. parapertussis also has the ability to circumvent these two neutrophil extracellular bactericidal activities. The lack of neutrophil degranulation was found dependent on the O antigen that targets the bacteria to cell lipid rafts, eventually avoiding the fusion of nascent phagosomes with specific and azurophilic granules. IgG opsonization overcame this inhibition of neutrophil degranulation. We further observed that B. parapertussis did not induce NETs release in resting neutrophils and inhibited NETs formation in response to phorbol myristate acetate (PMA) stimulation by a mechanism dependent on adenylate cyclase toxin (CyaA)-mediated inhibition of reactive oxygen species (ROS) generation. Thus, B. parapertussis modulates neutrophil bactericidal activity through two different mechanisms, one related to the lack of proper NETs-inducer stimuli and the other one related to an active inhibitory mechanism. Together with previous results these data suggest that B. parapertussis has the ability to subvert the main neutrophil bactericidal functions, inhibiting efficient clearance in non-immune hosts.


Assuntos
Anticorpos Antibacterianos/imunologia , Infecções por Bordetella/imunologia , Bordetella parapertussis/crescimento & desenvolvimento , Armadilhas Extracelulares/imunologia , Neutrófilos/imunologia , Infecções por Bordetella/microbiologia , Bordetella parapertussis/imunologia , Bordetella parapertussis/patogenicidade , Armadilhas Extracelulares/microbiologia , Humanos , Macrófagos/imunologia , Macrófagos/microbiologia , Microdomínios da Membrana , Neutrófilos/microbiologia , Fagocitose/imunologia , Fagossomos/imunologia
16.
Biomédica (Bogotá) ; 35(3): 302-305, jul.-sep. 2015. tab
Artigo em Espanhol | LILACS | ID: lil-765458

RESUMO

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.


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Bordetella/microbiologia , Infecções Oportunistas/microbiologia , Transplante de Medula Óssea , Bordetella bronchiseptica/isolamento & purificação , Bacteriemia/microbiologia , Recidiva , Síndromes Mielodisplásicas/terapia , Infecções por Bordetella/etiologia , Infecções Oportunistas/etiologia , Hospedeiro Imunocomprometido , Bordetella bronchiseptica/efeitos dos fármacos , Bacteriemia/etiologia , Pneumonia Bacteriana/etiologia , Pneumonia Bacteriana/microbiologia , Farmacorresistência Bacteriana Múltipla , Aloenxertos , Gastroenterite/etiologia , Gastroenterite/microbiologia , Doença Enxerto-Hospedeiro/tratamento farmacológico , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico
17.
mBio ; 6(3): e00500-15, 2015 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-26015497

RESUMO

UNLABELLED: Bordetella fimbriae (FIM) are generally considered to function as adhesins despite a lack of experimental evidence supporting this conclusion for Bordetella pertussis and evidence against a requirement for FIM in adherence of Bordetella bronchiseptica to mammalian cell lines. Using B. bronchiseptica and mice, we developed an in vivo adherence assay that revealed that FIM do function as critically important adhesins in the lower respiratory tract. In the first few days postinoculation, FIM-deficient B. bronchiseptica induced a more robust inflammatory response than wild-type bacteria did, suggesting that FIM, like filamentous hemagglutinin (FHA), allow B. bronchiseptica to suppress the innate immune response to infection. Localization analyses indicated that FIM are required for efficient attachment to airway epithelium, as bacteria lacking FIM localized to alveoli. FHA-deficient bacteria, in contrast, localized to airways. Bacteria unable to produce both FIM and FHA localized to alveoli and caused increased inflammation and histopathology identical to that caused by FIM-deficient bacteria, demonstrating that lack of FIM is epistatic to lack of FHA. Coinoculation experiments provided evidence that wild-type B. bronchiseptica suppresses inflammation locally within the respiratory tract and that both FHA and FIM are required for defense against clearance by the innate immune system. Altogether, our data suggest that FIM-mediated adherence to airway epithelium is a critical first step in Bordetella infection that allows FHA-dependent interactions to mediate tight adherence, suppression of inflammation, and resistance to inflammatory cell-mediated clearance. Our results suggest that mucosal antibodies capable of blocking FIM-mediated interactions could prevent bacterial colonization of the lower respiratory tract. IMPORTANCE: Although fimbriae (FIM) have been shown to be important mediators of adherence for many bacterial pathogens, there is surprisingly little experimental evidence supporting this role for Bordetella fimbria. Our results provide the first demonstration that Bordetella FIM function as adhesins in vivo, specifically to airway epithelium. Furthermore, our results suggest that FIM mediate initial interactions with airway epithelial cells that are followed by tight filamentous hemagglutinin (FHA)-mediated binding and that together, FIM and FHA allow Bordetella to suppress inflammation, leading to prolonged colonization. Given the shortcoming of the current acellular component pertussis (aP) vaccine in preventing colonization, these findings suggest that generation of antibodies capable of blocking FIM-mediated adherence could potentially prevent Bordetella colonization.


Assuntos
Adesinas Bacterianas/fisiologia , Aderência Bacteriana , Infecções por Bordetella/imunologia , Infecções por Bordetella/microbiologia , Bordetella bronchiseptica/fisiologia , Fímbrias Bacterianas/fisiologia , Adesinas Bacterianas/imunologia , Animais , Bordetella bronchiseptica/imunologia , Bordetella bronchiseptica/patogenicidade , Linhagem Celular , Células Epiteliais/microbiologia , Fímbrias Bacterianas/imunologia , Imunidade Inata , Pulmão/imunologia , Pulmão/microbiologia , Pulmão/ultraestrutura , Camundongos , Camundongos Endogâmicos BALB C , Mutação , Traqueia/microbiologia , Fatores de Virulência de Bordetella/imunologia
18.
J Cyst Fibros ; 14(5): E13-5, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25900817

RESUMO

Bordetella bronchiseptica is an opportunistic bacteria infecting the respiratory tract of patients with cystic fibrosis. We present a case of B. bronchiseptica chronic pulmonary infection and documentation of some phenotypic attributes of the clinical isolates allowing the microorganism to induce progressive respiratory degradation and chronic sputum colonization. We recommend implementing adequate treatment aiming eradication from the first isolation of this bacterium. We advise for practices that minimize opportunities for zoonotic transmission of B. bronchiseptica from family pets.


Assuntos
Infecções por Bordetella/microbiologia , Bordetella bronchiseptica/isolamento & purificação , Fibrose Cística/microbiologia , Infecções Respiratórias/microbiologia , Escarro/microbiologia , Western Blotting , Infecções por Bordetella/diagnóstico , Bordetella bronchiseptica/genética , Criança , Fibrose Cística/diagnóstico , DNA Bacteriano/análise , Seguimentos , Humanos , Masculino , Fenótipo , Infecções Respiratórias/diagnóstico , Fatores de Tempo , Tomografia Computadorizada por Raios X
19.
RNA Biol ; 12(2): 175-85, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25674816

RESUMO

Bordetella pertussis, the causative agent of human whooping cough (pertussis) produces a complex array of virulence factors in order to establish efficient infection in the host. The RNA chaperone Hfq and small regulatory RNAs are key players in posttranscriptional regulation in bacteria and have been shown to play an essential role in virulence of a broad spectrum of bacterial pathogens. This study represents the first attempt to characterize the Hfq regulon of the human pathogen B. pertussis under laboratory conditions as well as upon passage in the host and indicates that loss of Hfq has a profound effect on gene expression in B. pertussis. Comparative transcriptional profiling revealed that Hfq is required for expression of several virulence factors in B. pertussis cells including the Type III secretion system (T3SS). In striking contrast to the wt strain, T3SS did not become operational in the hfq mutant passaged either through mice or macrophages thereby proving that Hfq is required for the functionality of the B. pertussis T3SS. Likewise, expression of virulence factors vag8 and tcfA encoding autotransporter and tracheal colonization factor, respectively, was strongly reduced in the hfq mutant. Importantly, for the first time we demonstrate that B. pertussis T3SS can be activated upon contact with macrophage cells in vitro.


Assuntos
Proteínas de Bactérias/genética , Bordetella pertussis/genética , Bordetella pertussis/patogenicidade , Regulação Bacteriana da Expressão Gênica , Fator Proteico 1 do Hospedeiro/genética , RNA Bacteriano/genética , Sistemas de Secreção Tipo III/genética , Animais , Proteínas de Bactérias/metabolismo , Infecções por Bordetella/microbiologia , Bordetella pertussis/metabolismo , Linhagem Celular , Perfilação da Expressão Gênica , Fator Proteico 1 do Hospedeiro/deficiência , Interações Hospedeiro-Patógeno , Macrófagos/metabolismo , Macrófagos/microbiologia , Camundongos , RNA Bacteriano/metabolismo , Regulon , Transcriptoma , Sistemas de Secreção Tipo III/metabolismo , Sistemas de Secreção Tipo V/genética , Sistemas de Secreção Tipo V/metabolismo , Fatores de Virulência de Bordetella/genética , Fatores de Virulência de Bordetella/metabolismo
20.
Biomedica ; 35(3): 302-5, 2015.
Artigo em Espanhol | MEDLINE | ID: mdl-26849691
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