Nasal Immunization withBurkholderia multivoransOuter Membrane Proteins and the Mucosal Adjuvant Adamantylamide Dipeptide Confers Efficient Protection against Experimental Lung Infections withB. multivoransandB. cenocepacia

Bertot, Gustavo M.; Restelli, Marcela A.; Galanternik, L.; Urey, Rene C. Aranibar; Valvano, Miguel A.; Grinstein, S

doi:10.1128/iai.01668-06

Cited by 27 publications

(35 citation statements)

References 49 publications

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“…This is the first study that involves the use of recombinant subunit antigens to protect mice against Bcc bacteria. Previously, mice were protected from B. cenocepacia by using enriched OMPs that were administered intranasally as a nanoemulsion preparation (25,26). Both of those studies demonstrated the potential for OMPs as protective antigens but were carried out with unpurified OMP preparations, which are ill defined, rather than pure specific identified antigens.…”

Section: Discussionmentioning

confidence: 99%

“…Bacterial challenge studies were performed 2 weeks following booster vaccination, with immunosuppression by i.p. injection of 50 g of cyclophosphamide on days Ϫ1 and 4 of challenge (25). The immunized and nonimmunized mice were challenged with 4 ϫ 10 7 B. cenocepacia BC7 or B. multivorans LMG13010 bacteria suspended in 20 l of PBS instilled intranasally, and mice were maintained for 5 days before sacrifice by cervical dislocation.…”

Section: Figmentioning

confidence: 99%

“…The high level of antibiotic resistance combined with the continued acquisition of Bcc bacteria from the environment suggests that prevention of infection with a prophylactic vaccine may be a better approach than eradication of existing infections. Only two in vivo mouse vaccination studies have reported protection against the Bcc, both of which involved unpurified outer membrane protein (OMP) preparations (25,26). No vaccine antigens have been identified for the Bcc to date.…”

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confidence: 99%

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Linocin and OmpW Are Involved in Attachment of the Cystic Fibrosis-Associated Pathogen Burkholderia cepacia Complex to Lung Epithelial Cells and Protect Mice against Infection

McClean¹,

Healy

Collins³

et al. 2016

Infect Immun

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Members of the Burkholderia cepacia complex (Bcc) cause chronic opportunistic lung infections in people with cystic fibrosis (CF), resulting in a gradual lung function decline and, ultimately, patient death. The Bcc is a complex of 20 species and is rarely eradicated once a patient is colonized; therefore, vaccination may represent a better therapeutic option. We developed a new proteomics approach to identify bacterial proteins that are involved in the attachment of Bcc bacteria to lung epithelial cells. Fourteen proteins were reproducibly identified by two-dimensional gel electrophoresis from four Bcc strains representative of two Bcc species: Burkholderia cenocepacia, the most virulent, and B. multivorans, the most frequently acquired. Seven proteins were identified in both species, but only two were common to all four strains, linocin and OmpW. Both proteins were selected based on previously reported data on these proteins in other species. Escherichia coli strains expressing recombinant linocin and OmpW showed enhanced attachment (4.2-and 3.9-fold) to lung cells compared to the control, confirming that both proteins are involved in host cell attachment. Immunoproteomic analysis using serum from Bcc-colonized CF patients confirmed that both proteins elicit potent humoral responses in vivo. Mice immunized with either recombinant linocin or OmpW were protected from B. cenocepacia and B. multivorans challenge. Both antigens induced potent antigen-specific antibody responses and stimulated strong cytokine responses. In conclusion, our approach identified adhesins that induced excellent protection against two Bcc species and are promising vaccine candidates for a multisubunit vaccine. Furthermore, this study highlights the potential of our proteomics approach to identify potent antigens against other difficult pathogens.

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Section: Discussionmentioning

confidence: 99%

Section: Figmentioning

confidence: 99%

mentioning

confidence: 99%

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Linocin and OmpW Are Involved in Attachment of the Cystic Fibrosis-Associated Pathogen Burkholderia cepacia Complex to Lung Epithelial Cells and Protect Mice against Infection

McClean¹,

Healy

Collins³

et al. 2016

Infect Immun

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“…Some of these types of studies are under way, such as the development of molecules to inhibit the addition of Ara4N residues to lipid A (78) or the synthesis of L-glycero-D-mannoheptose sugars required for the LPS inner core oligosaccharide (43), as well as the manipulation of siderophores to act as "Trojan horses" for the delivery of antibiotics to bacteria (115). Furthermore a vaccine that prevents B. cenocepacia colonization in CF patients could provide additional benefit, and mucosal vaccines for this purpose are being developed (17,106).…”

Section: Discussionmentioning

confidence: 99%

A Decade of Burkholderia cenocepacia Virulence Determinant Research

2010

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The Burkholderia cepacia complex (Bcc) is a group of genetically related environmental bacteria that can cause chronic opportunistic infections in patients with cystic fibrosis (CF) and other underlying diseases. These infections are difficult to treat due to the inherent resistance of the bacteria to antibiotics. Bacteria can spread between CF patients through social contact and sometimes cause cepacia syndrome, a fatal pneumonia accompanied by septicemia. Burkholderia cenocepacia has been the focus of attention because initially it was the most common Bcc species isolated from patients with CF in North America and Europe. Today, B. cenocepacia, along with Burkholderia multivorans, is the most prevalent Bcc species in patients with CF. Given the progress that has been made in our understanding of B. cenocepacia over the past decade, we thought that it was an appropriate time to review our knowledge of the pathogenesis of B. cenocepacia, paying particular attention to the characterization of virulence determinants and the new tools that have been developed to study them. A common theme emerging from these studies is that B. cenocepacia establishes chronic infections in immunocompromised patients, which depend more on determinants mediating host niche adaptation than those involved directly in host cells and tissue damage.

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“…These models have been employed to investigate the virulence of different BCC species as well as of mutants to understand the importance of specific genes in disease. These infection models have also been applied to studies of host response, gene therapy, antimicrobial delivery, and immunization for prevention of BCC lung disease (6,32,51).…”

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confidence: 99%

Identification of Specific and Universal Virulence Factors in Burkholderia cenocepacia Strains by Using Multiple Infection Hosts

et al. 2009

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Over the past few decades, strains of the Burkholderia cepacia complex have emerged as important pathogens for patients suffering from cystic fibrosis. Identification of virulence factors and assessment of the pathogenic potential of Burkholderia strains have increased the need for appropriate infection models. In previous studies, different infection hosts, including mammals, nematodes, insects, and plants, have been used. At present, however, the extent to which the virulence factors required to infect different hosts overlap is not known. The aim of this study was to analyze the roles of various virulence factors of two closely related Burkholderia cenocepacia strains, H111 and the epidemic strain K56-2, in a multihost pathogenesis system using four different model organisms, namely, Caenorhabditis elegans, Galleria mellonella, the alfalfa plant, and mice or rats. We demonstrate that most of the identified virulence factors are specific for one of the infection models, and only three factors were found to be essential for full pathogenicity in several hosts: mutants defective in (i) quorum sensing, (ii) siderophore production, and (iii) lipopolysaccharide biosynthesis were attenuated in at least three of the infection models and thus may represent promising targets for the development of novel anti-infectives.The Burkholderia cepacia complex (BCC) comprises a group of the following 17 formally named bacterial species: Burkholderia cepacia,

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Nasal Immunization withBurkholderia multivoransOuter Membrane Proteins and the Mucosal Adjuvant Adamantylamide Dipeptide Confers Efficient Protection against Experimental Lung Infections withB. multivoransandB. cenocepacia

Cited by 27 publications

References 49 publications

Linocin and OmpW Are Involved in Attachment of the Cystic Fibrosis-Associated Pathogen Burkholderia cepacia Complex to Lung Epithelial Cells and Protect Mice against Infection

Linocin and OmpW Are Involved in Attachment of the Cystic Fibrosis-Associated Pathogen Burkholderia cepacia Complex to Lung Epithelial Cells and Protect Mice against Infection

A Decade of Burkholderia cenocepacia Virulence Determinant Research

Identification of Specific and Universal Virulence Factors in Burkholderia cenocepacia Strains by Using Multiple Infection Hosts

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