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 companies

• Total cost: €101 million

(From ND4BB report, 2013)

NDM-1 (NEW DELHI METALLO ΒETA-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 ANTIBIOTIC RESISTANCE

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