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EVOLUTION OF ANTIBIOTIC RESISTANCE
(TODAY’S WORLD vs ANTIBIOTIC RESISTANCE)
Ahmet VARIS
January 8th Thursday, 2015
OUTLINE•Statistics from US
Europe
Middle east
•Superbug from India
•Ongoing researches about evolution of antibiotic
resistance
•Databases
“Consequently, we face the prospect of returning to a
preantibiotic era, where an increasing number of
infections can no longer be treated effectively with
our current arsenal of drugs”
(Moly K. Gibson et al. Improved annotation of
antibiotic resistance determinants reveals microbial
resistomes cluster by ecology, 2014)
(http://www.cdc.gov/drugresistance/threat-report-2013/pdf/ar-threats-2013-508.pdf#page=13)
CDC (center for disease control and prevention) divide antibiotic
resistance 3 level
•Urgent: The highest risk for public health.
Ex: Clostridium difficile, Carbapenem-resistant Enterobacteriaceae
•Serious: These can be urgent if they effect public health.
Ex: Multidrug-resistant Acinetobacter, Fluconazole-resistant Candida
•Concerning: There are multiple treatment options for these
resistance.
Ex:Erythromycin-resistant Streptococcus Group A, Clindamycin-resistant
Streptococcus GroupB
WHAT ND4BB DOING?
•Every year 25 000 people die becaus of anti
biotic resistance in EU.
•Antibiotic resistance cost for EU is €1.5 billion.
•ND4BB is trying to collect acedemisions,
politics, companies.
•There are 3 projects for this aim
•COMBACTE, TRANSLOCATION, ENABLE
•COMBACTE:
• Creating a pan-European network of clinical sites
• It has a network of about 300 clnical sites from 34
countries
• Total cost: €250 million
•TRANSLOCATION:
• Getting drugs in to bugs and keeping them there
• 2/3 of deaths in EU coused by gram-negative
bacteria.
• Total cost: €29 million
•ENABLE:
• A Drug discovery platform
• This Project offer Access for universities and small
(From ND4BB report, 2013)
NDM-1 (NEW DELHI METALLOΒETA-LACTAMASE 1)
• Firstly investigate in india
•Most of scientist agreed that NDM-1 is the most
powerful resistance
• It is spread around the World and other bacteria
• Just two antibitics are cure for this resistance
(Figures are taken from Dvies&Davies, 2010)
Genome-wide analysis captures the determinants of the antibiotic cross-
resistance interaction network(Viktoria L. et.al 8 July 2014)Aims: To show
1) Convergent molecular evolution is commen across antibiotic treatments
2) Resistance, gaining by mutations enhance sensitivity to other drug
3) Antibiotic adaptation can partly be achieved without gain of novel function
RESULTS OF THIS EXPERIMENT
These are antibiotics which was used at experiment
PREDICTION OF ANTIBIOTIC RESISTANCE BY GENE EXPRESSION
PROFILES(Shingo S. et. al, 17 December 2014)
Antibiotics name Abbreviation Class Cellular target
Cefoperazone CPZ Cephalosporin, β-lactam Cell wall
Cefixime CFIX Cephalosporin, β-lactam Cell wall
Amikacin AMK Aminoglycoside Protein synthesis, 30S
Neomycin NM Aminoglycoside Protein synthesis, 30S
Doxycycline DOXY Tetracycline Protein synthesis, 30S
Chloramphenicol CP Protein synthesis, 50S
Azithromycin AZM Azalide, macrolide Protein synthesis, 50S
Trimethoprim TP Folic acid synthesis
Enoxacin ENX Quinolone DNA gyrase
Ciprofloxacin CPFX Quinolone DNA gyrase
Colistin CL Peptide Cell membrane
These are antibiotics which was used at experiment
DATABASES FOR ANTIBIOTICRESISTANCE
ARDB - Antibiotic Resistance Genes Database
REFERENCES
• Prediction of antibiotic resistance by gene expression profiles, Shingo Suziki, Takaaki Horinouchi & Chikara Furusawa,2014
• Improved annotation of antibiotic resistance determinants reveals microbial resistomes cluster by ecology, Molly K Gibson, Kevin J Forsberg &Gautam Dantas,2014
• Genome-wide analysis captures the determinants of the antibiotic cross-resistance interaction network, Viktor lazar et.al, 2014
• Streptococcus pneumoniae R6 interspecies transformation: genetic analysis of penicillin resistance determinants and genome-wide recombination events,Julia Sauerbier, Patrick Maurer, Martin Rieger and Regine Hakenbeck,2012
• http://www.cdc.gov/drugresistance/about.html
• http://www.searo.who.int/entity/antimicrobial_resistance/documents/en/
• http://www.imi.europa.eu/content/home
• The Comprehensive Antibiotic Resistance Database, Andrew G. Mcarthur et.al, 2013
THANK YOU