The DsbA‐DsbB Disulfide Bond Formation System of Burkholderia cepacia Is Involved in the Production of Protease and Alkaline Phosphatase, Motility, Metal Resistance, and Multi‐Drug Resistance

Abstract

Abstract:In Once considered as a phytopathogen, Burkholderia cepacia, a multi-drug-resistant bacteria, is now recognized as an important pathogen in the lung of patients with cystic fibrosis (CF) and can lead to severe pneumonia and death (15). B. cepacia strain KF1 isolated from a non-CF patient with pneumonia, produces extracellular metalloprotease in large quantities (37), and causes lung infections in mice on intratracheal inoculation (42). We have been analyzing the mechanism of protease production to explore its involvement in the pathogenesis.In a previous study, we showed that the protease-negative, lipase-positive mutant KFT1007, a Tn5-Tp insertion mutant of B. cepacia KF1, was impaired in the dsbB gene which encodes a membranebound disulfide bond oxidoreductase, DsbB, resulting in secretion of a premature and catalytically inactive form of protease (1). In Escherichia coli, DsbB couples with DsbA, a periplasmic disulfide bond oxidoreductase that directly makes S-S bonds on target molecules (26). Thus, the reduced-DsbA is reoxidized by oxidized-DsbB that is recycled with the aid of a respiratory electron transfer chain (14). The DsbA-DsbB circuit in E. coli is involved in flagellar basal body assembly (9), type IV pilin biogenesis (44), and the maturation of heat-stable enterotoxin (22) and alkaline phosphatase (10). In some Gram-negative bacteria, homologs of E. coli DsbA and their target proteins are found in Vibrio cholerae TcpG for enterotoxin (23)

Characterization of Two Homologous Disulfide Bond Systems Involved in Virulence Factor Biogenesis in Uropathogenic Escherichia coli CFT073

“…The protein forming the P-ring of E. coli flagella, FlgI, was one of the first DsbA substrates identified (10) and flagellum-mediated motility was subsequently demonstrated to require the presence of functional DsbA in several gram-negative pathogens, including Salmonella enterica (1), Proteus mirabilis (8), Erwinia carotovora subsp. atroseptica (9), Burkholderia cepacia (17), and Campylobacter jejuni (42). In Yersinia pestis, S. enterica, Shigella flexneri, and enteropathogenic E. coli, deletion of dsbA results in defective type III secretion, a major virulence mechanism employed by these enteric pathogens to manipulate the host during infection.…”

The Cpx Envelope Stress Response Affects Expression of the Type IV Bundle-Forming Pili of EnteropathogenicEscherichiacoli

“…Interestingly, a number of Cpx-regulated Dsb and DegP homologues have been implicated in the assembly of envelopelocalized virulence determinants in a variety of pathogens. These include type IV pili (TFP) in Vibrio cholerae (70) and Neisseria meningitidis (93), type III secretion systems (TTSS) in Shigella flexneri (99,(107)(108)(109) and Salmonella enterica serovar Typhimurium (27,60), and virulence determinants in Burkholderia cepacia (37), Erwinia carotovora (97), Pseudomonas aeruginosa (7,36,58), Bordetella pertussis (89), S. enterica serovar Typhimurium (27,46), S. flexneri (73), and Yersinia pestis (42,101). Further, DegP homologues have been implicated in virulence in Klebsiella pneumoniae (11) and Yersinia enterocolitica (57) and shown to be involved in the intracellular survival of Bartonella henselae (78), Y. enterocolitica (105), Legionella pneumophila (69), S. enterica serovar Typhimurium (4,29), and Haemophilus influenzae (13).…”

Development of tularemic scFv antibody fragments using phage display

“…The locus FTT1103 is predicted to encode a hypothetical lipoprotein which shares some similarity to DsbA proteins that catalyze disulfide bond formation. The activity of DsbA has been described to be important for the formation of various virulence factors including the bacterial type IV pili biogenesis, efflux pumps and function of type III secretion system [28][29][30][31][32][33]. However, the function of the protein FTT1103 remains unknown.…”