Burkholderia cenocepacia-induced delay of acidification and phagolysosomal fusion in cystic fibrosis transmembrane conductance regulator (CFTR)-defective macrophages

LaMothe, Julie; Valvano, Miguel A.

doi:10.1099/mic.0.2008/023200-0

Cited by 55 publications

(56 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For instance, in both Burkholderia cenocepacia and Mycobacterium tuberculosis, a delay in phagosome maturation is associated with intracellular survival (27,38). In contrast, we have shown that a marker of phagosome maturation, lysosome-associated membrane protein (LAMP), is recruited normally to the GBS-containing phagosome membrane, although we cannot currently rule out the possibility that other steps in phagosome maturation may be altered.…”

Section: Discussionmentioning

confidence: 69%

The CovS/CovR Acid Response Regulator Is Required for Intracellular Survival of Group B Streptococcus in Macrophages

et al. 2012

View full text Add to dashboard Cite

ABSTRACTGroup BStreptococcus(GBS) is a leading cause of neonatal meningitis and septicemia. The ability of this organism to survive inside phagocytic cells is poorly understood but thought to be an important step for the establishment of disease in the host. Here, we demonstrate that GBS shows prolonged survival within J774 macrophages and that the capacity to survive is not significantly changed across a diverse range of strains representing different serotypes, multilocus sequence types (MLST), and sites of clinical isolation. Using staining for the lysosome-associated membrane protein (LAMP) and by pharmacological inhibition of phagosome acidification, we demonstrate that streptococci reside in a phagosome and that acidification of the phagosome is required for GBS to survive intracellularly. Moreover, we show that the GBS two-component system CovS/CovR, which is the major acid response regulator in this organism, is required for survival inside the phagosome.

show abstract

Section: Discussionmentioning

confidence: 69%

The CovS/CovR Acid Response Regulator Is Required for Intracellular Survival of Group B Streptococcus in Macrophages

et al. 2012

View full text Add to dashboard Cite

show abstract

“…Recent studies of B. cenocepacia have indicated that this opportunistic pathogen may also replicate within a mature phagolysosome. However, this Bcc species delays the maturation of the bacteria-containing vacuole by 6 h (Lamothe et al, 2007;Lamothe & Valvano, 2008), possibly giving the bacterium time to make changes that would allow it to adapt to and survive within the phagolysosome (Tolman & Valvano, 2012 . B. cenocepacia MH1K was included as a control strain as it is known to cause a delay in phagosomal maturation in this cell line (Hamad et al, 2010).…”

Section: Bmcvs Do Not Exhibit Any Delay In Maturationmentioning

confidence: 99%

Burkholderia multivorans survival and trafficking within macrophages

Schmerk

Valvano

2013

Journal of Medical Microbiology

Self Cite

View full text Add to dashboard Cite

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.

show abstract

“…Using cell culture infection models, it was shown that B. cenocepacia can invade and survive in both professional and nonprofessional phagocytes, as well as in amoebae (4,46,47,61), by actively interfering with phagosome maturation (35) and delaying phagosome acidification (34). Recently, it was shown that the delay in acidification and phagolysosomal fusion is more compromised in cystic fibrosis transmembrane conductance regulator (CFTR)-negative macrophages (36) and that assembly of the NADPH-oxidase complex at the phagosomal membrane is compromised in B. cenocepacia-infected macrophages, which is also further delayed by inhibition of the CFTR (30). The ability of B. cenocepacia to invade and survive intracellularly as well as its ability to resist toxicity by reactive oxygen species in highly inflamed lungs (37) has been proposed to contribute significantly to its pathogenesis.…”

mentioning

confidence: 99%

Burkholderia cenocepaciaCreates an Intramacrophage Replication Niche in Zebrafish Embryos, Followed by Bacterial Dissemination and Establishment of Systemic Infection

et al. 2010

View full text Add to dashboard Cite

Bacteria belonging to the "Burkholderia cepacia complex" (Bcc) often cause fatal pulmonary infections in cystic fibrosis patients, yet little is know about the underlying molecular mechanisms. These Gram-negative bacteria can adopt an intracellular lifestyle, although their ability to replicate intracellularly has been difficult to demonstrate. Here we show that Bcc bacteria survive and multiply in macrophages of zebrafish embryos. Local dissemination by nonlytic release from infected cells was followed by bacteremia and extracellular replication. Burkholderia cenocepacia isolates belonging to the epidemic electrophoretic type 12 (ET12) lineage were highly virulent for the embryos; intravenous injection of <10 bacteria of strain K56-2 killed embryos within 3 days. However, small but significant differences between the clonal ET12 isolates K56-2, J2315, and BC7 were evident. In addition, the innate immune response in young embryos was sufficiently developed to control infection with other less virulent Bcc strains, such as Burkholderia vietnamiensis FC441 and Burkholderia stabilis LMG14294. A K56-2 cepR quorum-sensing regulator mutant was highly attenuated, and its ability to replicate and spread to neighboring cells was greatly reduced. Our data indicate that the zebrafish embryo is an excellent vertebrate model to dissect the molecular basis of intracellular replication and the early innate immune responses in this intricate host-pathogen interaction.

show abstract

Burkholderia cenocepacia-induced delay of acidification and phagolysosomal fusion in cystic fibrosis transmembrane conductance regulator (CFTR)-defective macrophages

Cited by 55 publications

References 53 publications

The CovS/CovR Acid Response Regulator Is Required for Intracellular Survival of Group B Streptococcus in Macrophages

The CovS/CovR Acid Response Regulator Is Required for Intracellular Survival of Group B Streptococcus in Macrophages

Burkholderia multivorans survival and trafficking within macrophages

Burkholderia cenocepaciaCreates an Intramacrophage Replication Niche in Zebrafish Embryos, Followed by Bacterial Dissemination and Establishment of Systemic Infection

Contact Info

Product

Resources

About