Virulence and Cellular Interactions of<i>Burkholderia multivorans</i>in Chronic Granulomatous Disease

Zelazny, Adrian M.; Ding, Li; Elloumi, Houda Zghal; Brinster, Lauren R.; Benedetti, Fran; Czapiga, Meggan; Ulrich, Ricky L.; Ballentine, Samuel; Goldberg, Joanna B.; Sampaio, Elizabeth P.; Holland, Steven M.

doi:10.1128/iai.00259-09

Cited by 16 publications

(22 citation statements)

References 44 publications

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“…Other groups have demonstrated that B. cenocepacia can induce strong production of numerous cytokines, including IL-1␤, TNF, monocyte chemoattractant protein 1 (MCP-1), IL-17, IFN-␥, IL-4, and IL-10 in cultured PBMCs from CF patients (47) and in neutropenic C57BL/6 mice or CFTR Ϫ/Ϫ knockout mice (31). Similarly, others have shown that another commonly isolated BCC member, B. multivorans, is capable of producing robust cytokine responses in mice (64), suggesting that recognition of BCC members is not confined to only one BCC member. The closely related, non-BCC, select agent species B. pseudomallei also induces TNF, IFN-␥, and IL-1␤ in C57BL/6 mice after intranasal inoculation (65,66).…”

Section: Discussionmentioning

confidence: 99%

Immune Recognition of the Epidemic Cystic Fibrosis Pathogen Burkholderia dolosa

et al. 2017

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Burkholderia dolosa caused an outbreak in the cystic fibrosis (CF) clinic at Boston Children's Hospital from 1998 to 2005 and led to the infection of over 40 patients, many of whom died due to complications from infection by this organism. To assess whether B. dolosa significantly contributes to disease or is recognized by the host immune response, mice were infected with a sequenced outbreak B. dolosa strain, AU0158, and responses were compared to those to the well-studied CF pathogen Pseudomonas aeruginosa. In parallel, mice were also infected with a polar flagellin mutant of B. dolosa to examine the role of flagella in B. dolosa lung colonization. The results showed a higher persistence in the host by B. dolosa strains, and yet, neutrophil recruitment and cytokine production were lower than those with P. aeruginosa. The ability of host immune cells to recognize B. dolosa was then assessed, B. dolosa induced a robust cytokine response in cultured cells, and this effect was dependent on the flagella only when bacteria were dead. Together, these results suggest that B. dolosa can be recognized by host cells in vitro but may avoid or suppress the host immune response in vivo through unknown mechanisms. B. dolosa was then compared to other Burkholderia species and found to induce similar levels of cytokine production despite being internalized by macrophages more than Burkholderia cenocepacia strains. These data suggest that B. dolosa AU0158 may act differently with host cells and is recognized differently by immune systems than are other Burkholderia strains or species.

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Section: Discussionmentioning

confidence: 99%

Immune Recognition of the Epidemic Cystic Fibrosis Pathogen Burkholderia dolosa

et al. 2017

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“…This result is similar to that seen when comparing the virulence of B. multivorans strains in mammalian infection models. In a study using C57BL/6 mice, a clinical B. multivorans isolate recovered from a patient with chronic granulomatous disease was far more virulent when compared with that of an environmental isolate (Zelazny et al, 2009). …”

Section: B Multivorans Atcc 17616 Induces Large-vacuole Formation Dumentioning

confidence: 99%

“…With few studies focusing on B. multivorans, there is still much to learn concerning the infective process of this bacterium, particularly with respect to its interaction with immune cells. To date, studies have demonstrated that B. multivorans can infect human lung epithelial cells (Duff et al, 2006;Moura et al, 2008), monocytes (Zelazny et al, 2009) and dendritic cells (MacDonald & Speert, 2008), and have elucidated some differences in B. cenocepacia and B. multivorans infections. During the infection of dendritic cells, only B. cenocepacia was able to impair cell function and induce necrosis, even though B. multivorans elicited a similar release of cytokines (MacDonald & Speert, 2008).…”

Section: Introductionmentioning

confidence: 99%

Burkholderia multivorans survival and trafficking within macrophages

Schmerk

Valvano

2013

Journal of Medical Microbiology

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Cystic fibrosis (CF) patients are at great risk of opportunistic lung infection, particularly by members of the Burkholderia cepacia complex (Bcc). This group of bacteria can cause damage to the lung tissue of infected patients and are difficult to eradicate due to their high levels of antibiotic resistance. Although the highly virulent Burkholderia cenocepacia has been the focus of virulence research for the past decade, Burkholderia multivorans is emerging as the most prevalent Bcc species infecting CF patients in North America. Despite several studies detailing the intramacrophage trafficking and survival of B. cenocepacia, no such data exist for B. multivorans.The results of this study demonstrated that the clinical CF isolates C5568 and C0514 and an environmental B. multivorans isolate, ATCC 17616, were able to replicate and survive within murine macrophages in a manner similar to that of B. cenocepacia strain K56-2. These strains were also able to survive but were unable to replicate within human THP-1 macrophages. Differences in macrophage uptake were observed among all three B. multivorans strains; these variances were attributed to major differences in O-antigen production. Unlike B. cenocepaciacontaining vacuoles, which delay phagosomal maturation in murine macrophages by 6 h, all B. multivorans-containing vacuoles co-localized with lysosome-associated membrane protein-1, a late endosome/lysosomal marker, and the lysosomal marker dextran within 2 h of uptake. Together, these results indicated that, whilst both Bcc species were able to survive and replicate within macrophages, they utilized different intramacrophage survival strategies. To observe differences in virulence, the strains were compared using the Galleria mellonella (wax worm) model. When compared with the B. multivorans strains tested, B. cenocepacia K56-2 was highly virulent in this model and killed all worms within 24 h when injected at 10 7 c.f.u. B. multivorans clinical isolates C5568 and C0514 were significantly more virulent than the soil isolate ATCC 17616, which was avirulent even when worms were injected with 10 7 c.f.u. These results suggest strain differences in the virulence of B. multivorans isolates.

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“…It has been speculated that B. cenocepacia can colonize both human lung epithelial and plant root cells through similar mechanisms responsible for recognition and adherence to host cells (Cao et al, 2001;Vial et al, 2011). Indeed, environmental B. cenocepacia strains, as well as environmental strains belonging to other BCC species, display an attenuated ability to invade or replicate in cellular models, in comparison with their clinical counterparts (Martin & Mohr, 2000;Keig et al, 2002;Pirone et al, 2008;Zelazny et al, 2009;Vial et al, 2010), but to date, the relationships between environmental bacteria and CF host cells have not been addressed. As suggested by Vial et al (2011), interactions with abnormal cells may trigger the pathogenic behaviour of B. cenocepacia strains in patients with genetic or immune deficiencies, and this could explain why opportunistic pathogens such as certain B. cenocepacia strains become pathogens in CF disease.…”

Section: Introductionmentioning

confidence: 99%