Burkholderia cepacia Produces a Hemolysin That Is Capable of Inducing Apoptosis and Degranulation of Mammalian Phagocytes

ABSTRACT Burkholderia cepacia is an opportunistic pathogen that has become a major threat to individuals with cystic fibrosis (CF). In approximately 20% of patients, pulmonary colonization with B. cepacia leads to cepacia syndrome, a fatal fulminating pneumonia sometimes associated with septicemia. It has been reported that culture filtrates of clinically derived strains of B. cepacia are hemolytic. In this study, we have characterized a factor which contributes to this hemolytic activity and is secreted from B. cepacia J2315, a representative of the virulent and highly transmissible strain belonging to the recently described genomovar III grouping. Biochemical data from the described purification method for this hemolysin allows us to hypothesize that the toxin is a lipopeptide. As demonstrated for other lipopeptide toxins, the hemolysin from B. cepacia was surface active and lowered the surface tension of high-pressure liquid chromatography-grade water from 72.96 to 29.8 mN m−1. Similar to reports for other pore-forming cytotoxins, low concentrations of the hemolysin were able to induce nucleosomal degradation consistent with apoptosis in human neutrophils and the mouse-derived macrophage-type cell line J774.2. Exposure of human neutrophils to higher concentrations of toxin resulted in increased activities of the neutrophil degranulation markers cathepsin G and elastase. Based on the results obtained in this study, we suggest a role that allows B. cepacia to thwart the immune response and a model of the events that may contribute to the severe inflammatory response in the lungs of CF patients.

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Antimicrobial activity of essential oils toward clinical and environmental strains of the opportunistic pathogen of Cystic Fibrosis patients Burkholderia cepacia complex

Planta Medica ◽

10.1055/s-0033-1352360 ◽

2013 ◽

Vol 79 (13) ◽

Author(s):

A Lo Nostro ◽

M Barnabei ◽

E Perrin ◽

A Bilia ◽

G Pesavento ◽

...

Keyword(s):

Cystic Fibrosis ◽

Antimicrobial Activity ◽

Essential Oils ◽

Burkholderia Cepacia ◽

Opportunistic Pathogen ◽

Burkholderia Cepacia Complex

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Burkholderia cepacia. [Descriptions of Fungi and Bacteria].

IMI Descriptions of Fungi and Bacteria ◽

10.1079/dfb/20056401216 ◽

1994 ◽

Author(s):

G. S. Saddler

Keyword(s):

Cystic Fibrosis ◽

Lycopersicon Esculentum ◽

Geographical Distribution ◽

Allium Cepa ◽

Leaf Spot ◽

Burkholderia Cepacia ◽

Allium Sativum ◽

Opportunistic Pathogen ◽

Agaricus Bitorquis ◽

Cultivated Mushroom

Abstract A description is provided for Burkholderia cepacia. Information is included on the disease caused by the organism, its transmission, geographical distribution, and hosts. HOSTS: Common host is Allium cepa, but can also cause disease in Allium sativum. Also identified as causing disease in Lycopersicon esculentum (63, 3168), a cavity disease of a cultivated mushroom (Agaricus bitorquis) (72, 5605) and a leaf spot on the a number of orchids including Cymbidium spp., Dendrobium sp. and Paphiopedilum spp. (66, 4326). The bacterium can also be found in soil, in clinical material, in disinfectant solutions and as an opportunistic pathogen of man and animals. It is gaining in significance as a major pathogen for sufferers of cystic fibrosis (Isles et al., 1984; McKevitt & Woods, 1984; Thomassen et al., 1985). DISEASE: Onion slippery skin; this is a rot of bulb scales, usually occurring at or near maturity, sometimes in storage. The bacterium does not appear to be strongly invasive, attacking plants that are damaged or weakened. Bacteria are thought to gain entry through the neck or leaf blades as the foliage falls over and the epidermis breaks, at maturity (64, 5550). GEOGRAPHICAL DISTRIBUTION: Worldwide. TRANSMISSION: Appears to be a soilborne wound pathogen.

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Pseudomonas aeruginosa isolates co-incubated with Acanthamoeba castellanii exhibit phenotypes similar to chronic cystic fibrosis isolates

10.1101/2020.02.25.964320 ◽

2020 ◽

Cited By ~ 2

Author(s):

Wai Leong ◽

Carla Lutz ◽

Jonathan Williams ◽

Yan Hong Poh ◽

Benny Yeo Ken Yee ◽

...

Keyword(s):

Cystic Fibrosis ◽

Pseudomonas Aeruginosa ◽

Late Stage ◽

Early Stage ◽

Acanthamoeba Castellanii ◽

Opportunistic Pathogen ◽

Human Neutrophils ◽

Phenotypic Traits ◽

Chronic Infections

AbstractThe opportunistic pathogen, Pseudomonas aeruginosa, is ubiquitous in the environment, and in humans is capable of causing acute and chronic infections. P. aeruginosa, when co-incubated with the bacterivorous amoeba, Acanthamoeba castellanii, for extended periods, produced genetic and phenotypic variants. Sequencing of late-stage amoeba-adapted P. aeruginosa isolates demonstrated single nucleotide polymorphisms within genes that encode known virulence factors, and this correlated with a reduction in expression of virulence traits. Virulence towards the nematode, Caenorhabditis elegans, was attenuated in late-stage amoeba-adapted P. aeruginosa compared to early stage amoeba-adapted and non-adapted counterparts. Late-stage amoeba-adapted P. aeruginosa lost competitive fitness compared to non-adapted counterparts when grown in nutrient rich media. However, non-adapted P. aeruginosa were rapidly cleared by amoeba predation, whereas late-stage amoeba-adapted isolates remained in higher numbers 24 h after ingestion by amoeba. In addition, there was reduced uptake by macrophage of amoeba-adapted isolates and reduced uptake by human neutrophils as well as increased survival in the presence of neutrophils. Our findings indicate that the selection imposed by amoeba on P. aeruginosa resulted in reduced virulence over time. Importantly, the genetic and phenotypic traits possessed by late-stage amoeba-adapted P. aeruginosa are similar to what is observed for isolates obtained from chronic cystic fibrosis infections. This notable overlap in adaptation to different host types suggests similar selection pressures among host cell types.Author SummaryPseudomonas aeruginosa is an opportunistic pathogen that causes both acute infections in plants and animals, including humans and also causes chronic infections in immune compromised and cystic fibrosis patients. This bacterium is commonly found in soils and water where bacteria are constantly under threat of being consumed by the bacterial predators, protozoa. To escape being killed, bacteria have evolved a suite of mechanisms that protect them from being consumed or digested. Here we examined the effect of long-term predation on the genotype and phenotypes expressed by P. aeruginosa. We show that long-term co-incubation with protozoa resulted in mutations in the bacteria that made them less pathogenic. This is particularly interesting as we see similar mutations arise in bacteria associated with chronic infections. Thus, predation by protozoa and long term colonization of the human host may represent similar environments that select for similar losses in gene functions.

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Complete Genome Sequence of Burkholderia cenocepacia K56-2, an Opportunistic Pathogen

Microbiology Resource Announcements ◽

10.1128/mra.01015-20 ◽

2020 ◽

Vol 9 (43) ◽

Author(s):

Inmaculada García-Romero ◽

Miguel A. Valvano

Keyword(s):

Cystic Fibrosis ◽

Genome Sequence ◽

Complete Genome Sequence ◽

Complete Genome ◽

Burkholderia Cepacia ◽

Opportunistic Pathogen ◽

Burkholderia Cenocepacia ◽

Content Type ◽

Advance Research

ABSTRACT Burkholderia cenocepacia K56-2, an opportunistic bacterium for people with cystic fibrosis (CF), belongs to the Burkholderia cepacia complex (Bcc) and is consistently used as a model pathogen. We describe here the closed genome sequence for this strain, which will help advance research in B. cenocepacia biology and omics studies.

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A Murine Model for Infection withBurkholderia cepacia with Sustained Persistence in the Spleen

Infection and Immunity ◽

10.1128/iai.67.8.4027-4032.1999 ◽

1999 ◽

Vol 67 (8) ◽

pp. 4027-4032 ◽

Cited By ~ 12

Author(s):

David P. Speert ◽

Barbara Steen ◽

Keith Halsey ◽

Eddie Kwan

Keyword(s):

Cystic Fibrosis ◽

Host Defense ◽

Murine Model ◽

Burkholderia Cepacia ◽

Systemic Infection ◽

Opportunistic Pathogen ◽

Granulomatous Disease ◽

Wild Type ◽

Murine Spleen ◽

Systemic Infections

ABSTRACT Burkholderia cepacia is an opportunistic pathogen that causes severe systemic infections in patients with chronic granulomatous disease (CGD) or with cystic fibrosis (CF), but its mechanisms of virulence are poorly understood. We developed a murine model of systemic infection in wild-type (WT) and gamma interferon knockout (GKO) BALB/c mice to facilitate dissection of components of pathogenicity and host defense. Both WT and GKO mice were susceptible to chronic splenic infection with B. cepacia, but not withPseudomonas aeruginosa. B. cepacia strains from patients with CGD persisted longer than those from CF patients. C57BL/6 mice were the most susceptible murine strain; bacteria persisted in the spleen for 2 months. DBA/2, BALB/c, and A/J strains of mice were relatively resistant to infection. Certain strains of B. cepacia complex can persist in the murine spleen after systemic infection; this may provide clues to its virulence in compromised hosts, such as those with CGD and CF.

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Suppurative Mediastinitis Secondary toBurkholderia Cepaciain a Patient with Cystic Fibrosis

Canadian Respiratory Journal ◽

10.1155/2006/495720 ◽

2006 ◽

Vol 13 (4) ◽

pp. 215-218 ◽

Cited By ~ 9

Author(s):

Ronald B George ◽

Yannick Cartier ◽

Alan G Casson ◽

Paul Hernandez

Keyword(s):

Cystic Fibrosis ◽

Weight Loss ◽

Case Report ◽

Lung Function ◽

Blood Cell ◽

Burkholderia Cepacia ◽

Clinical Course ◽

Opportunistic Pathogen ◽

Blood Cell Count ◽

Present Case Report

Burkholderia cepaciais an important opportunistic pathogen among patients with cystic fibrosis (CF); it is associated with deterioration of lung function, poor outcome following lung transplantation and increased mortality. Fever, an elevated white blood cell count, weight loss and an often fatal deterioration in pulmonary function characterize a particular clinical course, termed ‘Cepacia syndrome’. The present case report describes a 40-year-old man with CF who developed Cepacia syndrome complicated by suppurative mediastinitis, from whichB cepaciawas isolated. Despite optimal medical and surgical therapy, this patient succumbed to his illness. Those caring for patients with CF should be aware of this potentially catastrophic complication ofB cepaciainfection, especially in the setting of Cepacia syndrome.

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Cellulase Inhibits Burkholderia cepacia Biofilms on Diverse Prosthetic Materials

Polish Journal of Microbiology ◽

10.33073/pjm-2013-044 ◽

2013 ◽

Vol 62 (3) ◽

pp. 327-330 ◽

Cited By ~ 7

Author(s):

SATISH KUMAR RAJASEKHARAN ◽

SAMIRAJ RAMESH

Keyword(s):

Cystic Fibrosis ◽

Burkholderia Cepacia ◽

Selection Pressure ◽

Subsequent Development ◽

Opportunistic Pathogen ◽

Antibiofilm Activity ◽

Prosthetic Materials ◽

Antibiofilm Agents ◽

Implanted Devices

Burkholderia cepacia is an opportunistic pathogen causing infections in patients with cystic fibrosis. Patients with implanted devices are prone to B. cepacia infections due to its ability to grow as biofilms. Knowing the importance of polysaccharides in a biofilm, enzymes that degrade them were targeted as a possible candidate for antibiofilm agents. In this study, the antibiofilm potential of cellulase against B. cepacia biofilms formed on various prosthetic materials was tested. Cellulase exhibited significant antibiofilm activity against B. cepacia without having much action on its growth, thus ruling out the chance of selection pressure and subsequent development resistance.

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Western Faculty Profile: Dr. Miguel Valvano

Western Undergraduate Research Journal Health and Natural Sciences ◽

10.5206/wurjhns.2012-13.10 ◽

2012 ◽

Vol 3 (1) ◽

Author(s):

Suzy Kim

Keyword(s):

Cystic Fibrosis ◽

Cell Surface ◽

Burkholderia Cepacia ◽

Research Team ◽

Opportunistic Pathogen ◽

Host Cells ◽

Professor Emeritus ◽

Host Defenses ◽

Major Health ◽

Virulence Properties

Dr. Miguel Valvano is a Professor Emeritus in the Department of Microbiology and Immunology at Western University. He also holds an academic Chair of Microbiology and Infectious Diseases at the Centre for Infection and Immunity, Queen’s University Belfast, United Kingdom. His laboratory has become an international leader in molecular research aimed at dissecting key bacterial components that directly interact with host cells to cause infections. His research team focuses on two areas: how lipopolylsaccharide (LPS) assembles on the bacterial cell surface and protects bacteria from host defenses, and characterizing the virulence properties of Burkholderia cepacia, an opportunistic pathogen that causes major health problems in patients suffering from cystic fibrosis. Suzy Kim, a member of WURJ, had the opportunity to interview Dr. Valvano to learn more about his research, his path to Western and his career.

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Neutrophil Elastase Potentiates Cathepsin G-lnduced Platelet Activation

Thrombosis and Haemostasis ◽

10.1055/s-0038-1646319 ◽

1992 ◽

Vol 68 (05) ◽

pp. 570-576 ◽

Cited By ~ 20

Author(s):

Mary A Selak

Keyword(s):

Neutrophil Elastase ◽

Cell Activation ◽

Thromboxane A2 ◽

Creatine Phosphate ◽

Dense Granule ◽

Cathepsin G ◽

Dependent Manner ◽

Concentration Dependent Manner ◽

Low Concentrations ◽

High Concentrations

SummaryWe have previously demonstrated that human neutrophil cathepsin G is a strong platelet agonist that binds to a specific receptor. This work describes the effect of neutrophil elastase on cathepsin G-induced platelet responses. While platelets were not activated by high concentrations of neutrophil elastase by itself, elastase enhanced aggregation, secretion and calcium mobilization induced by low concentrations of cathepsin G. Platelet aggregation and secretion were potentiated in a concentration-dependent manner by neutrophil elastase with maximal responses observable at 200 nM. Enhancement was observed when elastase was preincubated with platelets for time intervals of 10–60 s prior to addition of a low concentration of cathepsin G and required catalytically-active elastase since phenylmethanesulphonyl fluoride-inhibited enzyme failed to potentiate cell activation. Neutrophil elastase potentiation of platelet responses induced by low concentrations of cathepsin G was markedly inhibited by creatine phosphate/creatine phosphokinase and/or indomethacin, indicating that the synergism between elastase and cathepsin G required the participation of ADP and thromboxane A2. On the other hand, platelet responses were not attenuated by the PAF antagonist BN 52021, signifying that PAF-acether did not play a role in elastase potentiation. At higher concentrations porcine pancreatic elastase exhibits similar effects to neutrophil elastase, demonstrating that the effect of elastase was not unique to the neutrophil protease. While neutrophil elastase failed to alter the ability of cathepsin G to hydrolyze a synthetic chromogenic substrate, preincubation of platelets with elastase increased the apparent affinity of cathepsin G binding to platelets. In contrast to their effect on cathepsin G-induced platelet responses, neither neutrophil nor pancreatic elasatse potentiated aggregation or dense granule release initiated by ADP, PAF-acether, arachidonic acid or U46619, a thromboxane A2 mimetic. Moreover, unlike its effect on cathepsin G, neutrophil elastase inhibited thrombin-induced responses. The current observations demonstrate that elastase can potentiate platelet responses mediated by low concentrations of cathepsin G, suggesting that both enzymes may function synergistically to activate platelets under conditions where neutrophil degranulation occurs.

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