Clinical outcome of Burkholderia cepacia complex infection in cystic fibrosis adults

Courtney, Jo‐Maree; Dunbar, K.; McDowell, Andrew; Moore, John E.; Warke, T.J.; Stevenson, Mike; Elborn, J. Stuart

doi:10.1016/j.jcf.2004.01.005

Cited by 124 publications

(99 citation statements)

References 36 publications

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“…However, most of these studies have focused on clinical outcomes in patients with epidemic and virulent genotypes, such as the B. cenocepacia ET-12 strain (33). Our results show that patients with chronic infections had lower lung func- Other studies have also suggested that the clinical outcomes for patients infected with B. cepacia complex are species dependent and that the host-pathogen interaction is also likely to play a role in virulence and clinical impacts (14,33,34). Jones and colleagues (33) reported excess mortality and accelerated clinical decline in patients with the ET-12 strain, whereas our study, which was dominated by sporadic B. cepacia complex infection, did not find increased rates of mortality or the need for lung transplantation.…”

Section: Discussionmentioning

confidence: 51%

Factors Influencing Acquisition of Burkholderia cepacia Complex Organisms in Patients with Cystic Fibrosis

et al. 2013

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dBurkholderia cepacia complex organisms are important transmissible pathogens found in cystic fibrosis (CF) patients. In recent years, the rates of cross-infection of epidemic strains have declined due to effective infection control efforts. However, cases of sporadic B. cepacia complex infection continue to occur in some centers. The acquisition pathways and clinical outcomes of sporadic B. cepacia complex infection are unclear. We sought to determine the patient clinical characteristics, outcomes, incidence, and genotypic relatedness for all cases of B. cepacia complex infection at two CF centers. We also sought to study the external conditions that influence the acquisition of infection. From 2001 to 2011, 67 individual organisms were cultured from the respiratory samples of 64 patients. Sixty-five percent of the patients were adults, in whom chronic infections were more common (68%) (P ‫؍‬ 0.006). The incidence of B. cepacia complex infection increased by a mean of 12% (95% confidence interval [CI], 3 to 23%) per year. The rates of transplantation and death were similar in the incident cases who developed chronic infection compared to those in patients with chronic Pseudomonas aeruginosa infection. Multilocus sequence typing revealed 50 individual strains from 65 isolates. Overall, 85% of the patients were infected with unique strains, suggesting sporadic acquisition of infection. The yearly incidence of nonepidemic B. cepacia complex infection was positively correlated with the amount of rainfall in the two sites examined: subtropical Brisbane (r ‫؍‬ 0.65, P ‫؍‬ 0.031) and tropical Townsville (r ‫؍‬ 0.82, P ‫؍‬ 0.002). This study demonstrates that despite strict cohort segregation, new cases of unrelated B. cepacia complex infection continue to occur. These data also support an environmental origin of infection and suggest that climate conditions may be associated with the acquisition of B. cepacia complex infections.

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Section: Discussionmentioning

confidence: 51%

Factors Influencing Acquisition of Burkholderia cepacia Complex Organisms in Patients with Cystic Fibrosis

et al. 2013

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“…The majority of BCC infections in CF patients (typically at least 70 %) are caused by Burkholderia cenocepacia and Burkholderia multivorans, and whilst B. cenocepacia previously accounted for the majority of cases, in recent years the incidence of B. multivorans infection has surpassed that of B. cenocepacia (Govan et al, 2007;LiPuma, 2010). B. cenocepacia typically has a greater impact on patient survival than B. multivorans (Courtney et al, 2004;Jones et al, 2004), although certain strains of B.…”

Section: Introductionmentioning

confidence: 99%

Growth on mannitol-rich media elicits a genome-wide transcriptional response in Burkholderia multivorans that impacts on multiple virulence traits in an exopolysaccharide-independent manner

et al. 2014

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In common with other members of the Burkholderia cepacia complex (BCC), Burkholderia multivorans is capable of producing exopolysaccharide (EPS) when grown on certain mannitolrich media. The significance of the resulting mucoid phenotype and the genome-wide response to mannitol has never been characterized despite its clinical relevance following the approval of a dried-powder preparation of mannitol as an inhaled osmolyte therapy for cystic fibrosis (CF) patients. In the present study we defined the transcriptional response of B. multivorans ATCC 17616, a model genome-sequenced strain of environmental origin, to growth on mannitol-rich yeast extract media (MYEM). EPS-dependent and -independent impact of MYEM on virulenceassociated traits was assessed in both strain ATCC 17616 and the CF isolate B. multivorans C1576. Our studies revealed a significant transcriptional response to MYEM encompassing approximately 23 % of predicted genes within the genome. Strikingly, this transcriptional response identified that EPS induction occurs in ATCC 17616 without the upregulation of the bce-I and bce-II EPS gene clusters, despite their pivotal role in EPS biosynthesis. Of approximately 20 differentially expressed putative virulence factors, 16 exhibited upregulation including flagella, ornibactin, oxidative stress proteins and phospholipases. MYEM-grown B. multivorans also exhibited enhanced motility, biofilm formation and epithelial cell invasion. In contrast to these potential virulence enhancements, MYEM-grown B. multivorans C1576 showed attenuated virulence in the Galleria mellonella infection model. All of the observed phenotypic responses occurred independently of EPS production, highlighting the profound impact that mannitol-based growth has on the physiology and virulence of B. multivorans.

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“…Burkholderia cenocepacia, a member of the Bcc, is one of the species most often recovered from CF patients worldwide and is also associated with the most severe infections (Brisse et al, 2004;LiPuma, 2005;Manno et al, 2004;Reik et al, 2005; Speert et al, 2002). Furthermore, B. cenocepacia infections in CF patients are associated with an accelerated decline in lung function as compared to other CF-related pathogens such as Pseudomonas aeruginosa (Courtney et al, 2004;Jones et al, 2004). The treatment of infection is difficult because this bacterium is multi-drug resistant (Zhou et al, 2007) and can be transmitted from person to person (Govan et al, 1993;LiPuma et al, 1990;Smith et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

Burkholderia cenocepacia requires RpoE for growth under stress conditions and delay of phagolysosomal fusion in macrophages

Flannagan

Valvano

2008

Microbiology

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Burkholderia cenocepacia is an opportunistic pathogen causing serious infections in patients with cystic fibrosis. The widespread distribution of this bacterium in the environment suggests that it must adapt to stress to be able to survive. We identified in B. cenocepacia K56-2 a gene predicted to encode RpoE, the extra-cytoplasmic stress response regulator. The rpoE gene is the first gene of a predicted operon encoding proteins homologous to RseA, RseB, MucD and a protein of unknown function. The genomic organization and the co-transcription of these genes were confirmed by PCR and RT-PCR. The mucD and rpoE genes were mutated, giving rise to B. cenocepacia RSF24 and RSF25, respectively. While mutant RSF24 did not demonstrate any growth defects under the conditions tested, RSF25 was compromised for growth under temperature (44 6C) and osmotic stress (426 mM NaCl). Expression of RpoE in trans could complement the osmotic growth defect but exacerbated temperature sensitivity in both RSF25 and wild-type K56-2. Inactivation of rpoE altered the bacterial cell surface, as indicated by increased binding of the fluorescent dye calcofluor white and by an altered outer-membrane protein profile. These cell surface changes were restored by complementation with a plasmid encoding rpoE. Macrophage infections in which bacterial colocalization with fluorescent dextran was examined demonstrated that the rpoE mutant could not delay the fusion of B. cenocepacia-containing vacuoles with lysosomes, in contrast to the parental strain K56-2. These data show that B. cenocepacia rpoE is required for bacterial growth under certain stress conditions and for the ability of intracellular bacteria to delay phagolysosomal fusion in macrophages. INTRODUCTIONThe Burkholderia cepacia complex (Bcc) comprises a group of nine closely related bacterial species that are phenotypically very similar but genetically distinct (Coenye et al., 2003;Mahenthiralingam et al., 2000). These bacteria are opportunistic pathogens that cause infections in immunocompromised individuals and often infect cystic fibrosis (CF) patients (Mahenthiralingam & Vandamme, 2005). Burkholderia cenocepacia, a member of the Bcc, is one of the species most often recovered from CF patients worldwide and is also associated with the most severe infections (Brisse et al., 2004;LiPuma, 2005;Manno et al., 2004;Reik et al., 2005; Speert et al., 2002). Furthermore, B. cenocepacia infections in CF patients are associated with an accelerated decline in lung function as compared to other CF-related pathogens such as Pseudomonas aeruginosa (Courtney et al., 2004;Jones et al., 2004). The treatment of infection is difficult because this bacterium is multi-drug resistant (Zhou et al., 2007) and can be transmitted from person to person (Govan et al., 1993;LiPuma et al., 1990;Smith et al., 1993). Infections are further complicated by the 'cepacia syndrome', a potentially fatal necrotizing pneumonia that occurs in a subset of patients (Isles et al., 1984;Thomassen et al., 1985).Although B. cenocepac...

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Clinical outcome of Burkholderia cepacia complex infection in cystic fibrosis adults

Abstract: BCC infection is associated with an accelerated decline in pulmonary function and BMI. Infection with a single B. cenocepacia strain was associated with a more rapid decline in lung function than those infected with either B. multivorans or P. aeruginosa.

Cited by 124 publications

References 36 publications

Factors Influencing Acquisition of Burkholderia cepacia Complex Organisms in Patients with Cystic Fibrosis

Factors Influencing Acquisition of Burkholderia cepacia Complex Organisms in Patients with Cystic Fibrosis

Growth on mannitol-rich media elicits a genome-wide transcriptional response in Burkholderia multivorans that impacts on multiple virulence traits in an exopolysaccharide-independent manner

Burkholderia cenocepacia requires RpoE for growth under stress conditions and delay of phagolysosomal fusion in macrophages

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