Current issues in Vancomycin-resistant enterococci Wee Gyo Lee, MD, PhD Department of Laboratory Medicine, Ajou University School of Medicine, Suwon, Korea.

Slides:



Advertisements
Similar presentations
Bacteria replication, recombination, and transformation
Advertisements

Will the Avian Flu Become the Next Epidemic?
Controlling Antibiotic Resistance in an Aquatic Environment 1 st Year PhD Student - Iona Paterson Primary Supervisor - Dr Andrew Hoyle Secondary Supervisor.
Mechanisms of Genetic Variation 1 16 Copyright © McGraw-Hill Global Education Holdings, LLC. Permission required for reproduction or display.
Global spread of antibiotic resistance: the example of New Delhi metallo-b-lactamase (NDM)-mediated carbapenem resistance Songzhen
Discover Biology FIFTH EDITION
SURVEILLANCE FOR GLYCOPEPTIDE-RESISTANT ENTEROCOCCI Drs N Bosman, T Nana & C Sriruttan CMID NHLS Dr Charlotte Sriruttan SASCM 3/11.
Lecture 3 MRSA Methicillin resistant S. aureus
Conjugative DNA transfer, antibiotic resistance and MDR bacteria.
Lecture 4 Vancomycin resistance VRE VISA / hVISA / VRSA Thursday – 1/17/2008.
AVIANAVIAN FLUFLU Ginny Codd Viruses: Infection and Ecology.
Vanderbilt University Department of Mathematics Mathematical Modelling and Challenges in the Development of Drug Resistance Mary Ann Horn Vanderbilt University.
Antibiotics and genetic variation in bacteria. Objectives Antibiotics Antibiotics don’t work against viruses. Antibiotics may be used to treat bacterial.
Transformation/Transfection
Viruses.
Bacterial Genetics Xiao-Kui GUO PhD.
Chemotherapy of bacterial infections. Part II.. Antibiotics – after-effects:
Genetic transfer and recombination
The evolution of antibiotic resistance Rob Knell / Lars Chittka.
Changes in bacterial traits Caused by: Changes in environmental conditions (only phenotypic changes) Changes in the genetic codes 1- Intermicrobial exchange.
Ranking of Antimicrobial Drugs According to Importance in Human Medicine John H. Powers, M.D. Lead Medical Officer Antimicrobial Drug Development and Resistance.
Molecular Basis of Vancomycin Resistance-Basic Science Paper Yashar Kalani Biochemistry 230.
Microbiology- a clinical approach by Anthony Strelkauskas et al Chapter 20: Antibiotic resistance.
Beyond Phylogeny: Evolutionary analysis of a mosaic pathogen Dr Rosalind Harding Departments of Zoology and Statistics, Oxford University,UK.
RESTRICTION ENDONUCLEASES RESTRICTION ENDONUCLEASES CUT AT SPECIFIC SITES & LEAVE STICKY ENDS EcoR1EcoR1 animation Leave “sticky ends” that can be used.
CHAPTER 5 The Genetics of Bacteria and Their Viruses CHAPTER 5 The Genetics of Bacteria and Their Viruses Copyright 2008 © W H Freeman and Company.
Xin Wang, Ph.D Meningitis Laboratory CDC 1. 2  Human commensal bacterium and also one of the common pathogens causing bacterial meningitis.  12 serogroups.
Viruses Gene Regulation results in differential Gene Expression, leading to cell Specialization.
EVOLUTION & SPECIATION. Microevolution. What is it? changes in the gene pool of a population over time which result in relatively small changes to the.
LECTURE CONNECTIONS 1 | Introduction to Genetics © 2009 W. H. Freeman and Company.
REASSORTMENT OF INFLUENZA VIRUS
NAJRAN UNIVERSITY College of Medicine NAJRAN UNIVERSITY College of Medicine Microbiology &Immunology Course Lecture No. 6 Microbiology &Immunology Course.
Unit III Information Essential to Life Processes Learning Goal 3 Explain how the processing of genetic information is imperfect and is a source of genetic.
Antibiotic Resistance
Dominant and Recessive Dominance Table 3. Alleles sequence of DNA any of several forms of a gene determine the genotype (genetic constitution of an organism.
RESULTS INTRODUCTION METHODS CONCLUSION  Since the early 90’s Enterococcus faecium resistant to Glycopeptides (GRE) have emerged in several French hospitals.
Definitions Learning Objectives At the end of this lecture you (will) be able to: Understand definitions used in infectious disease epidemiology.
THINGS TO BE DISCUSSED Multi resistance antimicrobials Effects of some Antibiotics Research article Case study Future Horizons.
Bacterial Genetics Prof. Dr. Asem Shehabi Faculty of Medicine University of Jordan.
The case of Clavibacter michiganensis ssp. michiganensis
Bacteria CHAPTER 27. You must know  The key ways in which prokaryotes differ from eukaryotes with respect to genome, membrane- bound organelles, size,
How I deal with an outbreak? Prof Bertrand SOUWEINE Medical ICU Clermont-Ferrand France ISICEM March 2009.
Bioinformatics for Clinical Microbiology and Molecular Epidemiology: From Databases to Population Genetics João André Carriço 7 July 2010 Ciência 2010.
2. Centers for Disease Control and Prevention (CDC), Atlanta, GA, USA
MICROBIOLOGIA GENERALE
Antibiotic Resistance
Outbreak Investigations
Evolution of Populations
Antibiotic Resistance
REDUCED RATES OF VANCOMYCIN RESISTANT ENTEROCOCCI (VRE) COLONIZATION
Horizontal gene transfer and the history of life
Genetic Control of Metabolism
Chapter 15: How Organisms Evolve.
Molecular Mechanisms of Antibacterial Multidrug Resistance
High prevalence of multidrug-resistant Pneumococcal molecular epidemiology network clones among Streptococcus pneumoniae isolates from adult patients.
Intrahost Genome Alterations in Enterohemorrhagic Escherichia coli
Genome-based insights into the evolution of enterococci
Emergence of vancomycin-resistant enterococci in a tertiary hospital in Crete, Greece: a cluster of cases and prevalence study on intestinal colonisation 
Extra chromosomal Agents Transposable elements
MIC distribution and inoculum effect of LY333328: a study of vancomycin-susceptible and VanA-type and VanC-type enterococci obtained from intensive care.
Gene Regulation results in differential Gene Expression, leading to cell Specialization Viruses
Vancomycin resistance emerging in a clonal outbreak caused by ampicillin-resistant Enterococcus faecium  Stig Harthug, A. Digranes, O. Hope, B.E. Kristiansen,
Sohyun Cho (Gabi) Frye Lab
Clonality among ampicillin-resistant Enterococcus faecium isolates in Sweden and relationship with ciprofloxacin resistance  E. Torell, J. Kühn, B. Olsson-Liljeauist,
Cell Transformation.
Higher Biology Unit 1: 1.7 Evolution.
Surveillance of intestinal colonization and of infection by vancomycin-resistant enterococci in hospitalized cancer patients  Florence Moulin, Sandrine.
The principles of genetic association
Dissemination of Antibiotic Resistance Genomes
Presentation transcript:

Current issues in Vancomycin-resistant enterococci Wee Gyo Lee, MD, PhD Department of Laboratory Medicine, Ajou University School of Medicine, Suwon, Korea

Background Mechanisms ▫Biochemical ▫Genetic Epidemiology ▫Global ▫Molecular Current issues

Background Enterococci: - major nosocomial pathogens - Vancomycin-resistant enterococci (VRE) 1986, first VRE in France ≥ % of enterococci - exchange genetic information among themselves and with other genera - in 2002, VRSA with vanA gene  11 cases

Biochemical Mechanism Alternative pathway for peptidoglycan synthesis 1. Synthesis of low-affinity precursors: D-Ala-D-Lac or D-Ala-D-Ser 2. Elimination of precursors normally produced in the chromosome by the host

Cell membrane Cell membrane VanSVanS Vancomycin ATP PP ADPVanRVanR ORF1ORF1 ORF2ORF2vanRvanRvanSvanSvanHvanHvanAvanAvanXvanXvanYvanYvanZvanZ Lactate D-Ala-D-Lac UDP-MurNAc-L-Ala-D-Glu-L-Lys- vanH vanA vanX Pyruvate D-AlaD-Ala-D-Ala Cell wall synthesis

Genetic Mechanism

Global Epidemiology Differences between Europe & USA Europe ▫widespread use of avoparcin (VM analogue) ▫High VRE colonisation rate: pigs, calves, turkeys ▫Asymptomatic carriage among healthy people is common ▫Only a few nosocomial outbreaks have been reported

USA ▫Glycopeptides: never been used in the farm animals industry ▫VRE colonisation among healthy people is extremely rare. ▫VRE appear to have first emerged as nosocomial infection. ▫The greater use of vancomycin in hospitals ▫The establishment of VRE endemicity  Outbreaks of single strain  monoclonal nature  multiple enterococcal strains  polyclonal endemicity

Korea ▫widespread use of avoparcin (VM analogue) ▫VRE colonisation in animals is common. ▫No transmission of VRE between human & poultry ▫Rare reservoir of VRE among healthy people ▫The spread of VRE: similarly to USA ▫The greater use of vancomycin ▫Polyclonal endemic state in Korea

ChromosomeTn1546 with vanA gene cluster Tn typing PFGE, MLST, MLVA Molecular Epidemiology

Transposon typing ▫vanA gene cluster is carried as a part of Tn1546 ▫Analysis of genetic variation of Tn1546 ▫Majority of the variations – integrations of insertion sequences with or without a deletion at the insertion site ▫Horizontal transfer Strain typing ▫PFGE, MLST, MLVA ▫Clonal spread, genetic evolution

Strain Typing MLST (Multilocus sequence typing) ▫Identifying alleles from DNA sequences of internal fragments of 7 house keeping genes ▫Allellic profile:  the alleles at each of the seven housekeeping genes  E. faecium ▫Sequence type (ST):  Defined by the allelic profile.  ST36: ▫Objective & readily comparable between Lab.

E. faeicum ▫adk (adenylate kinase) ▫atpA (ATP synthase) ▫ddl (D-alanine-D-alanine ligase) ▫gyd (glyceraldehyde-3-phosphate dehydrogenase) ▫gdh (glucose-6-phosphate dehydrogenase) ▫purK (phosphoribosylaminoimidazol carboxylase ATPase subunit) ▫pstS (phosphate ATP-binding cassette transporter)

MLST of VRE in the world

Current Issues Clonal Complex 17 ▫“Epidemic” genetic complex-17 : derived from secondary founder ST-17 ▫Epidemic-virulent, hospital-adapted strains ▫Ampicillin resistance (MICs ≥ 16mg/l): uniformly ▫Higher levels of quinolone resistance ▫Presence of the E. feacium pathogenicity island carrying the esp gene: majority ▫Either resistant to glycopeptides  Such strains were already spread before they acquired the van gene

“Genetic capitalism” – hospital adapted strain capable of surviving in hospital settings 1 st : ampicillin R – selective advantage in hospitals  acquisition of PAI – facilitated transmission  horizontal transfer of vanA/B genes  has emerged on several continents

1, animal isolates; 2, human community surveillance isolates; 3, surveillance (feces); 4, clinical isolates; 5, isolates from documented hospital outbreaks Global distribution of complex-17 isolates

Clonal complex-17 VRE : Ko. JCM 43, 2005 Lee. Letters in AM 43, 2006 국내 E. faecium 분포

VanB phenotype-vanA genotype Impaired resistance to Teicoplanin (I or S) Mechanism: still not clear 1. Point mutations of vanS - Three point mutations in the putative sensor domain of vanS 2. Lacked vanY or vanZ - not affected to Vm resistance - vanZ: required for Teicoplanin resistance

East asian area: Japan, Korea, & Taiwan Japan & Taiwan ▫First reported by Hashimoto et al. 2000, Japan. ▫In Japan & Taiwan: mutation of vanS ▫Gu et al. 2009, Taiwan, 52.2% of VRE  No mutation of vanS  Impairment of vanY/vanZ  MLST: different genetic background? Korea ▫Eom et al 2004: mutation of vanS ▫Lee et al 2004, Song et al 2006: Impairment of vanY/vanZ Recently, increased prevalence

VanC VRE with vanA gene VanC VRE ▫Intrinsic constitutive resistance ▫Species-specific vanC1 : E.gallinarum vanC2 : E.casseliflavus vanC3 : E.flavescens ▫Located in the chromosome ▫Peptidoglycan precursors : D-Ala-D-Ser ▫MIC : Vm 2-32 mg/L, Te  1 mg/L

Clinical significance Not required special infection control measures Emerging vanA containing VanC VRE ▫VanA phenotype ▫Potential reservoirs of transmissible van genes ▫Require infection control ▫Genotypic testing

Thank You