Presentation is loading. Please wait.

Presentation is loading. Please wait.

John R W Govan University of Edinburgh Medical School

Published byCameron Daniel Modified over 9 years ago

Similar presentations

Presentation on theme: "John R W Govan University of Edinburgh Medical School"— Presentation transcript:

1 John R W Govan University of Edinburgh Medical School
Cystic fibrosis John R W Govan University of Edinburgh Medical School

2 What is cystic fibrosis?
Significance of respiratory infections Problem pathogens and new technologies

3 Cystic Fibrosis Cystic Fibrosis is the most common, life-threatening, recessively inherited disease of Caucasian populations Carrier rate of 1 in 25 and incidence rate of I in 2500 live births UK ~ 7500 babies, children and young adults. Cause. Mutations in gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) gene which encodes an epithelial chloride channel. Survival. Progressive lung disease secondary to respiratory infection is the main cause of morbidity and mortality.

4

5 CFTR, defective mucocilary clearance and salt-sensitive antimicrobial peptides (defensins)

6 Bacterial Pathogens in CF
Limited spectrum Age related sequence Haemophilus influenzae Staphylococcus aureus Pseudomonas aeruginosa Burkholderia cepacia complex S. maltophilia/A. xylosoxidans

7 ‘Burkholderia cepacia’ – the pathogen
Swamp foot in US marines Nosocomial infections due to contaminated fluids. ICUs Chronic granulomatous disease. Inherited loss of neutrophil oxidative killing leading to fatal lung infection ‘Cepacia syndrome’ in cystic fibrosis – fatal unexpected pneumonia with bacteraemia in 20-30% of infected patients

8 Edinburgh – 1986 Glass & Govan J Infect 1986; 13:157-158.
Fatal cepacia syndrome in 9-year-old CF female. No transfer to CF sibling. Genomovar III (B. cenocepacia) J415, cblA and bcesm –ve

9 Transmission of B. cepacia Govan et al. Lancet 1993
Spread within and between CF clinics includes social contacts. Outcome fatal but unpredictable Leper-like infection control -- segregation and anxiety! Virtually untreatable

10 ‘Burkholderia cepacia’ how resistant?
Biodegradation of synthetic herbicides and petroleum oxidants. Panresistance to antibiotics. Can utilise penicillin as nutrient! Resistance to natural antimicrobial peptides – (defensins) of amoebae, insects, animals and humans – explains CGD.

11 B. cepacia as an animal pathogen Berriatua et al 2000
B. cepacia as an animal pathogen Berriatua et al J Clin Microbiol 2001;39: 990-4 Untreatable outbreak of ovine mastitis No environmental source identified Genomovar III responsible

12 Bacterial hybrids or new taxons. Simpson et al
Bacterial hybrids or new taxons? Simpson et al. J Antimicrob Chemother1994; 34:

13 ‘Burkholderia cepacia complex ’
Evolving taxonomy At least 10 distinct genomovars recognised by polyphasic taxonomy and RecA PCR All genomovars isolated from CF patients However, gvr II (B. multivorans) and III (B. cenocepacia) account for 90% of isolates and most transmission – includes the ET12 lineage

14 ‘B. cepacia’ AMMD Parke & Gurion-Sherman J Phyt 2002

15 The biopesticide issue -update
‘There is no evidence that CF patients acquire B. cepacia from the environment – CF isolates are different’ - biopesticide developer 1999 Not true – even clonal - Govan, Vandamme & Balandreau ASM News 2000;66:124 New use rule. Fed Reg 2002

16 Antibiotics in trouble!

17 Evolution of bacterial resistance and pathogenesis – a two way process
Common perception: Bacterial pathogens accumulate resistance to antibiotics -- rendering them virtually untreatable . MRSA and vancomycin-resistant Enterococcus faecium What’s also happening: Inherently resistant environmental bacteria acquire opportunistic virulence for plant, human and animal hosts. Burkholderia cepacia complex Bacteriology IDG

18 Eshwar Mahenthiralingam
Collaborations B. cepacia B. pseudomallei Eshwar Mahenthiralingam Richard Titball Petra Oyson Peter Vandamme Ty Pitt John Govan C.A. Hart Mahidol University Sirirurg Songsivillai

19

20 B. cepacia - general features J2315 - Edinburgh ET12 isolate
914 bp 80.9 % 82 62.8 % 92,661 bp plasmid 2 1 x 16S-23S-5S 982 bp 86.6 % 773 66.9 % 875,977 bp Chr. 3 73 5 66 tRNA 67.3 % 66.7 % G+C content 6 x 971 bp 87.0 % 7,226 8,055,782 bp Total 1x 4 x rRNA 995 bp 950 bp Av. gene length 87.8 % Coding density 2,840 3,531 Genes 3,217,062 bp 3,870,082 bp Size Chr. 2 Chr. 1

21 B. cepacia – chromosome 2 – LHF analysis
fatty-acid metabolism + transport polysaccharide biosynthesis phage rRNA chemotaxis, helicase, drug efflux? haemolysin -related protein phospholipases phage, haemolysin drug efflux, catabolism, regulators plasmid conjugation system cell-surface protein

22 B. cepacia and the neutrophil: dose dependent and synergistic inflamation
Lipopeptide toxin (haemolysin) induces apoptosis at low concentrations and degranulation at high concentrations. B. cepacia LPS induces potent TNF and IL-8 response and primes neutrophil to a damaging response to other microbes and ‘procedures’.

23 Looking ahead Are all B. cepacia complex potentially virulent and transmissible? Transplantation, segregation and biopesticides issues The promise of genomics and proteomics ‘B. cepacia’ identification at local level. False positives 10%; False negatives 30%.

24 Identification of B. cepacia complex
Variable colonial morphology Selective media not selective enough: Mast Cepacia medium or BCSA (Henry et al 1997). Accuracy of commercial identification kits?

25 ID of B. cepacia complex by API20NE, Vitek NFC/GNI and BBL Crystal
Accuracy varies from %. API20NE most accurate. None of the systems identified genomovar VI Only API20NE identified the Glasgow epidemic strain (gvr II, B. multivorans) and the epidemic ET12 lineage (gvr III, B. cenocepacia).

26 Some people’s idea of microbiologists?

27

28 IBCWG (http://go.to/cepacia/)
“…as a forum for clinicians and scientists interested in advancing knowledge of B. cepacia infection and colonisation in persons with CF through the collegial exchange of information and promotion of coordinated approaches to research…”

29 “B. cepacia”: other bacteria
Many other bacteria are (mis)identified as B. cepacia Known species: P. aeruginosa S. maltophilia R. pickettii A. xylosoxidans B. hinzii Brevundimonas spp. Chryseobacterium spp. Enterobacteriaceae

Download ppt "John R W Govan University of Edinburgh Medical School"

Similar presentations

Antimicrobial Prescribing in the Management of COPD

Antimicrobial Prescribing in the Management of COPD
Controlling Antibiotic Resistance in an Aquatic Environment 1 st Year PhD Student - Iona Paterson Primary Supervisor - Dr Andrew Hoyle Secondary Supervisor.

Controlling Antibiotic Resistance in an Aquatic Environment 1 st Year PhD Student - Iona Paterson Primary Supervisor - Dr Andrew Hoyle Secondary Supervisor.
Lateral Transfer. Donating Genes Mutation often disrupts the function of a gene Gene transfer is a way to give new functions to the recipient cell Thus,

Lateral Transfer. Donating Genes Mutation often disrupts the function of a gene Gene transfer is a way to give new functions to the recipient cell Thus,
Introduction to Microbiology H. GEE. MD, FRCOG Hon. Assoc. Clinical Professor University of Warwick.

Introduction to Microbiology H. GEE. MD, FRCOG Hon. Assoc. Clinical Professor University of Warwick.
PSEUDOMONAS.

PSEUDOMONAS.
Pseudomonas and Nonfermenters  Opportunistic Pathogens of Plants, Animals, and Humans  Many Taxonomic Changes in Last Decade  Clinically Important.

Pseudomonas and Nonfermenters  Opportunistic Pathogens of Plants, Animals, and Humans  Many Taxonomic Changes in Last Decade  Clinically Important.
Pseudomonas and Nonfermenters D.  Opportunistic Pathogens of Plants, Animals, and Humans  Many Taxonomic Changes in Last Decade  Clinically Important.

Pseudomonas and Nonfermenters D.  Opportunistic Pathogens of Plants, Animals, and Humans  Many Taxonomic Changes in Last Decade  Clinically Important.
Cystic Fibrosis Fred Hill, MA, RRT. Overview Cystic fibrosis is the most common fatal, inherited disease in the U. S. Cystic fibrosis is the most common.

Cystic Fibrosis Fred Hill, MA, RRT. Overview Cystic fibrosis is the most common fatal, inherited disease in the U. S. Cystic fibrosis is the most common.
G aps, challenges and opportunities Theo Verheij University Medical Center Utrecht Lower Respiratory Tract Infections in Primary Care.

G aps, challenges and opportunities Theo Verheij University Medical Center Utrecht Lower Respiratory Tract Infections in Primary Care.
Cystic Fibrosis Pathogens Activate Ca 2+ -dependent mitogen-activated Protein Kinase Signaling Pathways in Airway Epithelial Cells by Aubrey Osborne and.

Cystic Fibrosis Pathogens Activate Ca 2+ -dependent mitogen-activated Protein Kinase Signaling Pathways in Airway Epithelial Cells by Aubrey Osborne and.
Antimicrobial Susceptibility Testing – Part II

Antimicrobial Susceptibility Testing – Part II
Tiffany Rimmer.  CF is the most common lethal autosomal recessive genetic disease in Caucasians.  It affects over 30,000 individuals in the United States.

Tiffany Rimmer.  CF is the most common lethal autosomal recessive genetic disease in Caucasians.  It affects over 30,000 individuals in the United States.
Pathogenic Bacteriology Introduction. What the class will cover: Clinically significant bacteria Morphological characteristics Biochemical characteristics.

Pathogenic Bacteriology Introduction. What the class will cover: Clinically significant bacteria Morphological characteristics Biochemical characteristics.
The genetics of cystic fibrosis

The genetics of cystic fibrosis
1 RETROSPECTIVE EVALUATION OF THE PATIENTS WITH CYSTIC FIBROSIS DR.LALE PULAT SEREN ZEYNEP KAMİL MATERNITY AND CHILDREN’S TRAINING AND RESEARCH HOSPITAL.

1 RETROSPECTIVE EVALUATION OF THE PATIENTS WITH CYSTIC FIBROSIS DR.LALE PULAT SEREN ZEYNEP KAMİL MATERNITY AND CHILDREN’S TRAINING AND RESEARCH HOSPITAL.
Antibiotics and genetic variation in bacteria. Objectives Antibiotics Antibiotics don’t work against viruses. Antibiotics may be used to treat bacterial.

Antibiotics and genetic variation in bacteria. Objectives Antibiotics Antibiotics don’t work against viruses. Antibiotics may be used to treat bacterial.
Aynaz Taheri 1 C. Gyles and P. Boerlin. * Transfer of foreign DNA * Mechanisms of transfer of DNA * Mobile genetic elements (MGE) * MGEs in the virulence.

Aynaz Taheri 1 C. Gyles and P. Boerlin. * Transfer of foreign DNA * Mechanisms of transfer of DNA * Mobile genetic elements (MGE) * MGEs in the virulence.
Berkeley Fial Michaela McNiff.  Someone gets Cystic Fibrosis when they inherit two mutated genes – one from each parent.  The CF gene is on chromosome.

Berkeley Fial Michaela McNiff.  Someone gets Cystic Fibrosis when they inherit two mutated genes – one from each parent.  The CF gene is on chromosome.
The Child with Cystic Fibrosis Lydia Burland. Learning Outcomes By the end of the session you should;  Know the basic physiology underlying CF  Recognise.

The Child with Cystic Fibrosis Lydia Burland. Learning Outcomes By the end of the session you should;  Know the basic physiology underlying CF  Recognise.
Global Antibiotic Use and the Rise of Resistance BioQUEST Summer Workshop June 12 – 13, 2010 Julie Seiter, Oakland Community College Ethel Stanley, BioQUEST,

Global Antibiotic Use and the Rise of Resistance BioQUEST Summer Workshop June 12 – 13, 2010 Julie Seiter, Oakland Community College Ethel Stanley, BioQUEST,

Similar presentations

Ads by Google