Burkholderia mallei cellular interactions in a respiratory cell model.
Burkholderia mallei is a facultative intracellular pathogen that survives and replicates in phagocytic cell lines. The bacterial burden recovered from naïve BALB/c mice infected by intranasal delivery indicated that B. mallei persists in the lower respiratory system. To address whether B. mallei invades respiratory non-professional phagocytes, this study utilized A549 and LA-4 respiratory epithelial cells and demonstrated that B. mallei possesses the capacity to adhere poorly to, but not to invade, these cells. Furthermore, it was found that B. mallei was taken up by the murine alveolar macrophage cell line MH-S following serum coating, an attribute suggestive of complement- or Fc receptor-mediated uptake. Invasion/intracellular survival assays of B. mallei-infected MH-S cells demonstrated decreased intracellular survival, whilst a type III secretion system effector bopA mutant strain survived longer than the wild-type. Evaluation of the potential mechanism(s) responsible for efficient clearing of intracellular organisms demonstrated comparable levels of caspase-3 in both the wild-type and bopA mutant with characteristics consistent with apoptosis of infected MH-S cells. Furthermore, challenge of BALB/c mice with the bopA mutant by the intranasal route resulted in increased survival. Overall, these data suggest that B. mallei induces apoptotic cell death, whilst the BopA effector protein participates in intracellular survival.
Department of Clinical Laboratory Sciences, University of Texas Medical Branch, Galveston, TX 77555-1070, USA.|Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555-1070, USA.
Gregory C
GC
Whitlock
Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555-1070, USA.
Gustavo A
GA
Valbuena
Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555-1070, USA.
Vsevolod L
VL
Popov
Department of Pediatrics, University of Texas Medical Branch, Galveston, TX 77555-1070, USA.
Barbara M
BM
Judy
Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, TX 77555-1070, USA.|Department of Pediatrics, University of Texas Medical Branch, Galveston, TX 77555-1070, USA.|Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555-1070, USA.
D Mark
DM
Estes
Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, TX 77555-1070, USA.|Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555-1070, USA.|Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555-1070, USA.
Alfredo G
AG
Torres
D000230:Adenocarcinoma; D000818:Animals; D001422:Bacterial Adhesion; D019121:Burkholderia Infections / Q000473:pathology*; D042726:Burkholderia mallei / Q000166:cytology / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity; D016923:Cell Death; D045744:Cell Line, Tumor; D002470:Cell Survival; D017931:DNA Primers; D006801:Humans; D008168:Lung / Q000382:microbiology; D008175:Lung Neoplasms; D016676:Macrophages, Alveolar / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D016133:Polymerase Chain Reaction; D020545:Respiratory Mucosa / Q000382:microbiology; D014774:Virulence
D017931:DNA Primers