Burkholderia cepacia complex infection in patients with cystic fibrosis

Mahenthiralingam, Eshwar; Baldwin, Amy; Vandamme, Peter

doi:10.1099/0022-1317-51-7-533

Cited by 193 publications

(189 citation statements)

References 23 publications

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“…Importantly, about 20% ofthe patients colonized by B. cepacia eventually succumb to the cepacia syndrome characterized by acute necrotizing pneumonia, bacteriemia and septicemia (5). B. cepacia consists of several genomovars, and genomovar III, that has been given the binomial species name of B. cenocepacia (6), has been described as the most relevant for pathogenesis in humans (7).…”

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confidence: 99%

Iron Availability Influences Aggregation, Biofilm, Adhesion and Invasion ofPseudomonas AeruginosaandBurkholderia Cenocepacia

Berlutti

Morea²,

Battistoni

et al. 2005

Int J Immunopathol Pharmacol

109

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Pseudomonas aeruginosa and Burkholderia cenocepacia are predominant opportunistic pathogens in cystic fibrosis (CF) patients. In healthy humans the lower respiratory tract as well as all mucosa, contains a very low free iron concentration (10-18 M), while in CF patients' sputum iron concentration is very high, showing a median value of 63x10-6 M. Accumulation of catalytic reactive iron heavily contributes to subsequent clinical complications in the lung disorders by the production of reactive oxygen species and increases bacterial growth and virulence. The data reported in this study indicate that low iron concentration (Fe 3 + 1 JA.M) induced free-living forms and motility both in P. aeruginosa and B. cenocepacia, while high iron concentrations (Fe 3 + 10 and 100 tJ.M) stimulated aggregation and biofilm formation already in the fluid phases, so demonstrating that aggregation and biofllm formation are positively iron-modulated in these bacteria. Moreover, the different morphological forms (free-living, aggregates and biofllm) showed different capabilities of adhering and invading the bronchial cell line A549. P. aeruginosa PA01 aggregates, and mostly biofllm, exerted the highest adhesion efficiency, while B. cenocepacia PV1 aggregates or biofilm the lowest. A significant reduction in invasion efficiency by P. aeruginosa biofilm and a significant increase in cell internalization by B. cenocepacia biofllm has been reported. Therefore, the iron availability is an important signal to which P. aeruginosa and B. cenocepacia counteract by leaving the motile free-living forms and entering into a new lifestyle, i.e, biofllm. These data could contribute to explain that the ironoverload of the sputum of CF patients, inducing nonmotile forms, aggregates and biofllm, may facilitate penetration of host epithelial barriers contributing to the establishment of infection, colonization, persistence and systemic spread of these opportunistic pathogens.Pseudomonas aeruginosa is a ubiquitous Gramnegative motile bacterium found in different environments such as soil, freshwater and marine habitat. Moreover, P. aeruginosa is the predominant opportunistic pathogen in cystic fibrosis (CF) patients, as the lungs of >90% of all CF patients are colonized by this bacterium (1). Chronic colonization of P. aeruginosa in CF patient airways is a major source of morbidity and mortality (2) leading to epithelial surface damage and airway plugging which results in a decrease of pulmonary function (3).Although not as prevalent as P. aeruginosa, Burkholderia cepacia is another important opportunistic respiratory pathogen in CF patients (2),

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confidence: 99%

Iron Availability Influences Aggregation, Biofilm, Adhesion and Invasion ofPseudomonas AeruginosaandBurkholderia Cenocepacia

Berlutti

Morea²,

Battistoni

et al. 2005

Int J Immunopathol Pharmacol

109

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“…They cause a rapid decline in pulmonary function, with ensuing increased morbidity and mortality. 3 Because only a limited number of antibiotics are effective against Bcc, complete eradication of infection is rare. 4 Taxonomic studies based on traditional phenotypic and genotypic tests 5e8 have demonstrated that Bcc includes nine genomic species or genomovars: B. cepacia (formerly genomovar I), Burkholderia multivorans (genomovar II), Burkholderia cenocepacia (genomovar III, divided into four recA clusters, III-A, III-B, III-C and III-D), Burkholderia stabilis (genomovar IV), Burkholderia vietnamiensis (genomovar V), Burkholderia dolosa (genomovar VI), Burkholderia ambifaria (genomovar VII), Burkholderia anthina (genomovar VIII) and Burkholderia pyrrocinia (genomovar IX).…”

Section: Introductionmentioning

confidence: 99%

Burkholderia respiratory tract infections in Italian patients with cystic fibrosis: Molecular characterization

Allice

Scutera

Chirillo

et al. 2006

Journal of Infection

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Summary Objectives: To characterize by molecular techniques Burkholderia strains responsible for respiratory tract infections in cystic fibrosis (CF) patients (children and adults), to assign the Burkholderia cepacia complex (Bcc) isolates to a genomovar and to assess the presence of cblA and esmR genes in bacteria. Unique or sequential Burkholderia isolates (n ¼ 48) that had been collected from eight CF children and 17 adults over several (4e6) years were investigated; moreover 11 reference strains were analyzed. Methods: The microorganisms were identified by using biochemical methods, genotyped by pulse field gel electrophoresis (PFGE) and random-amplified polymorphic DNA fingerprintingePCR (RAPDePCR), and assessed by PCR assays for the genomovar and cblA and esmR genes of Bcc. Results: Among isolates 70.8% were identified as Bcc genomovar III-A; one child was infected by Burkholderia ambifaria and four adults were colonized with Burkholderia gladioli. The cblA gene was not detected in any of the isolates, while the esmR gene was detected in the 52.1% of the strains, all belonging to genomovar III-A. Conclusion: Molecular analysis of strains revealed in CF patients a colonization with a persistent Burkholderia flora with strains of one genotype. The prevalence of Bcc of genomovar III-A in the two categories of patients and of B. gladioli in four adults demonstrated that transmission may have occurred between subjects. Moreover the B. ambifaria infection demonstrated in a child may be environmentally derived.

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“…One group of closely related species, the Burkholderia cepacia complex (BCC), are noted for their ability to cause opportunistic infections in humans, particularly in patients with cystic fibrosis (CF) (LiPuma, 1998;Coenye et al, 2001;Speert, 2002;Mahenthiralingam et al, 2008). Among the members of the BCC, Burkholderia cenocepacia is the most prevalent in both CF and non-CF infections (Vandamme et al, 1997;Coenye et al, 2001;Mahenthiralingam et al, 2002Mahenthiralingam et al, , 2005Reik et al, 2005). The complete genome sequence has recently been determined for a strain of B. cenocepacia that caused an epidemic among CF patients in Canada and the UK (Holden et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

The pobA gene of Burkholderia cenocepacia encodes a Group I Sfp-type phosphopantetheinyltransferase required for biosynthesis of the siderophores ornibactin and pyochelin

et al. 2011

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The opportunistic pathogen Burkholderia cenocepacia produces the siderophores ornibactin and pyochelin under iron-restricted conditions. Biosynthesis of both siderophores requires the involvement of non-ribosomal peptide synthetases (NRPSs). Using a transposon containing the lacZ reporter gene, two B. cenocepacia mutants were isolated which were deficient in siderophore production. Mutant IW10 was shown to produce normal amounts of ornibactin but only trace amounts of pyochelin, whereas synthesis of both siderophores was abolished in AHA27. Growth of AHA27, but not IW10, was inhibited under iron-restricted conditions. In both mutants, the transposon had integrated into the pobA gene, which encodes a polypeptide exhibiting similarity to the Sfp-type phosphopantetheinyltransferases (PPTases). These enzymes are responsible for activation of NRPSs by the covalent attachment of the 4′-phosphopantetheine (P-pant) moiety of coenzyme A. Previously characterized PPTase genes from other bacteria were shown to efficiently complement both mutants for siderophore production when provided in trans. The B. cenocepacia pobA gene was also able to efficiently complement an Escherichia coli entD mutant for production of the siderophore enterobactin. Using mutant IW10, in which the lacZ gene carried by the transposon is inserted in the same orientation as pobA, it was shown that pobA is not appreciably iron-regulated. Finally, we confirmed that Sfp-type bacterial PPTases can be subdivided into two distinct groups, and we present the amino acid signature sequences which characterize each of these groups.

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Burkholderia cepacia complex infection in patients with cystic fibrosis

Cited by 193 publications

References 23 publications

Iron Availability Influences Aggregation, Biofilm, Adhesion and Invasion ofPseudomonas AeruginosaandBurkholderia Cenocepacia

Iron Availability Influences Aggregation, Biofilm, Adhesion and Invasion ofPseudomonas AeruginosaandBurkholderia Cenocepacia

Burkholderia respiratory tract infections in Italian patients with cystic fibrosis: Molecular characterization

The pobA gene of Burkholderia cenocepacia encodes a Group I Sfp-type phosphopantetheinyltransferase required for biosynthesis of the siderophores ornibactin and pyochelin

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