Functional Quorum Sensing Systems are Maintained during Chronic Burkholderia cepacia Complex Infections in Patients with Cystic Fibrosis

McKeon, Suzanne; Nguyen, D.T.; Viteri, Duber Frey; Zlosnik, James E. A.; Sokol, Pamela A.

doi:10.1093/infdis/jiq054

Cited by 22 publications

(16 citation statements)

References 44 publications

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“…In contrast to P. aeruginosa , McKeon et al showed that B. cenocepacia QS mutants were far less frequent during chronic infection. Only 1 in 22 patients harboured mutations in both QS Bcc systems, cepR and cciR, which would have an effect on function, the loss in QS function did not appear to confer a competitive advantage for B. cenocepacia in vivo [ 106 ]. Recent data showed that a triple knock-out mutant in J2315 of cepl, cciR and Burkholderia diffusible signal factor, had reduced biofilm forming capacities, was more susceptible to antibiotics, and was less virulent in C. elegans than the wild type strain [ 107 ], which may explain the lack of QS mutants in chronically colonised CF patients.…”

Section: Quorum Sensingmentioning

confidence: 99%

Bacterial Adaptation during Chronic Respiratory Infections

Cullen¹,

McClean²

2015

Pathogens

138

145

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Chronic lung infections are associated with increased morbidity and mortality for individuals with underlying respiratory conditions such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). The process of chronic colonisation allows pathogens to adapt over time to cope with changing selection pressures, co-infecting species and antimicrobial therapies. These adaptations can occur due to environmental pressures in the lung such as inflammatory responses, hypoxia, nutrient deficiency, osmolarity, low pH and antibiotic therapies. Phenotypic adaptations in bacterial pathogens from acute to chronic infection include, but are not limited to, antibiotic resistance, exopolysaccharide production (mucoidy), loss in motility, formation of small colony variants, increased mutation rate, quorum sensing and altered production of virulence factors associated with chronic infection. The evolution of Pseudomonas aeruginosa during chronic lung infection has been widely studied. More recently, the adaptations that other chronically colonising respiratory pathogens, including Staphylococcus aureus, Burkholderia cepacia complex and Haemophilus influenzae undergo during chronic infection have also been investigated. This review aims to examine the adaptations utilised by different bacterial pathogens to aid in their evolution from acute to chronic pathogens of the immunocompromised lung including CF and COPD.

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Section: Quorum Sensingmentioning

confidence: 99%

Bacterial Adaptation during Chronic Respiratory Infections

Cullen¹,

McClean²

2015

Pathogens

138

145

View full text Add to dashboard Cite

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“…Interestingly, all but one isolate produced AHLs. Further analyses revealed that there is a selective advantage for strains with a functional CepIR system and that mutations in these genes are therefore very rare 75 . Additional evidence for an important role of AHL-mediated QS was obtained by analyzing the transcriptome of two clonal variants of B. cenocepacia isolated during long-term colonization of a CF patient 76 .…”

Section: The Role Of Qs In Pathogenicity Of Members Of the Bccmentioning

confidence: 99%

Two quorum sensing systems control biofilm formation and virulence in members of theBurkholderia cepaciacomplex

et al. 2013

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The Burkholderia cepacia complex (Bcc) consists of 17 closely related species that are problematic opportunistic bacterial pathogens for cystic fibrosis patients and immunocompromised individuals. These bacteria are capable of utilizing two different chemical languages: N-acyl homoserine lactones (AHLs) and cis-2-unsaturated fatty acids. Here we summarize the current knowledge of the underlying molecular architectures of these communication systems, showing how they are interlinked and discussing how they regulate overlapping as well as specific sets of genes. A particular focus is laid on the role of these signaling systems in the formation of biofilms, which are believed to be highly important for chronic infections. We review genes that have been implicated in the sessile lifestyle of this group of bacteria. The new emerging role of the intracellular second messenger cyclic dimeric guanosine monophosphate (c-di-GMP) as a downstream regulator of the fatty acid signaling cascade and as a key factor in biofilm formation is also discussed.

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“…in ET12 strains) [5], [7]–[10]. Both systems appear to be maintained during chronic infections in CF patients [11]. CepI primarily synthetizes oxanoyl-homoserine lactone (C8-HSL) and minor amounts of hexanoyl-HSL (C6-HSL), whereas CciI is primarily responsible for the synthesis of C6-HSL with lesser amounts of C8-HSL [8].…”

Section: Introductionmentioning

confidence: 99%

Phenotypic and Genotypic Characterisation of Burkholderia cenocepacia J2315 Mutants Affected in Homoserine Lactone and Diffusible Signal Factor-Based Quorum Sensing Systems Suggests Interplay between Both Types of Systems

et al. 2013

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Many putative virulence factors of Burkholderia cenocepacia are controlled by various quorum sensing (QS) circuits. These QS systems either use N-acyl homoserine lactones (AHL) or cis-2-dodecenoic acid (“Burkholderia diffusible signal factor”, BDSF) as signalling molecules. Previous work suggested that there is little cross-talk between both types of systems. We constructed mutants in B. cenocepacia strain J2315, in which genes encoding CepI (BCAM1870), CciI (BCAM0239a) and the BDSF synthase (BCAM0581) were inactivated, and also constructed double (ΔcepIΔBCAM0581, ΔcciIΔBCAM0581 and ΔcepIΔcciI) mutants and a triple (ΔcepIΔcciIΔBCAM0581) mutant. Subsequently we investigated phenotypic properties (antibiotic susceptibility, biofilm formation, production of AHL and BDSF, protease activity and virulence in Caenorhabditis elegans) and measured gene expression in these mutants, and this in the presence and absence of added BDSF, AHL or both. The triple mutant was significantly more affected in biofilm formation, antimicrobial susceptibility, virulence in C. elegans, and protease production than either the single or double mutants. The ΔBCAM0581 mutant and the ΔcepIΔBCAM0581 and ΔcciIΔBCAM0581 double mutants produced significantly less AHL compared to the WT strain and the ΔcepI and ΔcciI single mutant, respectively. The expression of cepI and cciI in ΔBCAM0581, was approximately 3-fold and 7-fold (p<0.05) lower than in the WT, respectively. The observed differences in AHL production, expression of cepI and cciI and QS-controlled phenotypes in the ΔBCAM0581 mutant could (at least partially) be restored by addition of BDSF. Our data suggest that, in B. cenocepacia J2315, AHL and BDSF-based QS systems co-regulate the same set of genes, regulate different sets of genes that are involved in the same phenotypes and/or that the BDSF system controls the AHL-based QS system. As the expression of the gene encoding the C6-HSL synthase CciI (and to a lesser extent the C8-HSL synthase CepI) is partially controlled by BDSF, it seems likely that the BDSF QS systems controls AHL production through this system.

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Functional Quorum Sensing Systems are Maintained during Chronic Burkholderia cepacia Complex Infections in Patients with Cystic Fibrosis

Cited by 22 publications

References 44 publications

Bacterial Adaptation during Chronic Respiratory Infections

Bacterial Adaptation during Chronic Respiratory Infections

Two quorum sensing systems control biofilm formation and virulence in members of theBurkholderia cepaciacomplex

Phenotypic and Genotypic Characterisation of Burkholderia cenocepacia J2315 Mutants Affected in Homoserine Lactone and Diffusible Signal Factor-Based Quorum Sensing Systems Suggests Interplay between Both Types of Systems

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