Burkholderia cepacia is resistant to the antimicrobial activity of airway epithelial cells

Baird, R M; Brown, Helen; Smith, Anthony W.; Watson, Malcolm L.

doi:10.1016/s0162-3109(99)00122-8

Cited by 33 publications

(19 citation statements)

References 13 publications

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“…Various bacterial factors have also been proposed as potential virulence factors, including a potent haemolysin [10], a siderophore [11], surface lipopolysaccharide [12,13], an extracellular protease [14], lipases [15], a melaninlike pigment [16], as well as the cable pili-associated 22-kDa adhesin which has now been shown to mediate bacterial binding to mucin, cells and lung sections of CF patients [17±20]. The ability of some B. cepacia to invade and survive in epithelial cells and macrophages [21±23] and the resistance of this micro-organism to airway epithelial cell antimicrobial activity and to oxidative killing by phagocytes [21,24] may also contribute to virulence.…”

Section: Introductionmentioning

confidence: 99%

Immunolocalisation of Burkholderia cepacia in the lungs of cystic fibrosis patients

Sajjan¹,

Corey

Humar

et al. 2001

Journal of Medical Microbiology

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Infection by Burkholderia cepacia is sometimes fatal in patients with cystic ®brosis (CF), as the organism can cause necrotising pneumonia and septicaemia (the cepacia syndrome), and is resistant to antibiotics. To increase knowledge of the pathogenesis of lung infection, the present study investigated the distribution of B. cepacia in lung explants from nine CF recipients of double lung transplants, of which six were colonised with both B. cepacia and Pseudomonas aeruginosa and the other three with P. aeruginosa only. In one case, explants of the donor lung (allograft) became available after the patient succumbed post-operatively to the cepacia syndrome. Further autopsy sections were examined from two patients who had chronic and then acute infection with B. cepacia. A speci®c antibody reactive with all ®ve genomovars of the B. cepacia complex and another antibody speci®c for the 22-kDa adhesin of cable pili, were used to localise bacteria in situ. In chronic infection, the organisms were diffusely distributed, but most concentrated in hyperplastic bronchiolar epithelium, in¯amed peribronchial and perivascular areas, between adjacent airway epithelial cells and in pathologically thickened alveolar septae and luminal macrophages. In acute infections the distribution was more focal, with B. cepacia on injured airway surfaces and in sites of pneumonia and abscess formation. In autopsy sections from one of the patients with chronic, then acute infection, B. cepacia was also observed in the lumen of blood capillaries. These results suggest that B. cepacia has the capacity to be highly invasive, migrating from the airways across the epithelial barrier to invade the lung parenchyma and capillaries, thereby initiating septicaemia.

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Section: Introductionmentioning

confidence: 99%

Immunolocalisation of Burkholderia cepacia in the lungs of cystic fibrosis patients

Sajjan¹,

Corey

Humar

et al. 2001

Journal of Medical Microbiology

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“…Members of the Bcc are reported to cause infections in up to 5% of cystic fibrosis (CF) patients in the world, which is significant, as CF patients colonized with Bcc experience a more rapid decline than do those colonized with the more commonly acquired pathogen Pseudomonas aeruginosa (14,15). Once a patient is colonized with Bcc bacteria, these bacteria are rarely eradicated due to the resistance of the Bcc to antibiotics (16) and antimicrobial peptides (17,18). Strict segregation measures have limited the patient-to-patient spread of the most virulent species, B. cenocepacia (19).…”

mentioning

confidence: 99%

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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“…In the last 2 decades, cationic antimicrobial peptides have become appealing as potential new therapeutic agents for a variety of conditions (20). Although cationic peptides display promising activity against P. aeruginosa and other CF pathogens (56), they are generally ineffective against members of the BCC (3,45,46,49).…”

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confidence: 99%

In Vitro Susceptibility of Burkholderia vietnamiensis to Aminoglycosides

Jassem

Zlosnik

Henry

et al. 2011

Antimicrob Agents Chemother

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Burkholderia cepacia complex (BCC) bacteria are opportunistic pathogens that can cause severe disease in cystic fibrosis (CF) patients and other immunocompromised individuals and are typically multidrug resistant. Here we observed that unlike other BCC species, most environmental and clinical Burkholderia vietnamiensis isolates were intrinsically susceptible to aminoglycosides but not to cationic antimicrobial peptides or polymyxin B. Furthermore, strains acquired aminoglycoside resistance during chronic CF infection, a phenomenon that could be induced under tobramycin or azithromycin pressure in vitro. In comparing susceptible and resistant B. vietnamiensis isolates, no gross differences in lipopolysaccharide structure were observed, all had lipid A-associated 4-amino-4-deoxy-L-arabinose residues, and all were resistant to the permeabilizing effects of aminoglycosides, a measure of drug entry via self-promoted uptake. However, susceptible isolates accumulated 5 to 6 times more gentamicin than a resistant isolate, and aminoglycoside susceptibility increased in the presence of an efflux pump inhibitor. B. vietnamiensis is therefore unusual among BCC bacteria in its susceptibility to aminoglycosides and capacity to acquire resistance. Aminoglycoside resistance appears to be due to decreased cellular accumulation as a result of active efflux.

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Burkholderia cepacia is resistant to the antimicrobial activity of airway epithelial cells

Cited by 33 publications

References 13 publications

Immunolocalisation of Burkholderia cepacia in the lungs of cystic fibrosis patients

Immunolocalisation of Burkholderia cepacia in the lungs of cystic fibrosis patients

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

In Vitro Susceptibility of Burkholderia vietnamiensis to Aminoglycosides

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