A COMPREHENSIVE AND AN UPDATE DATABASE ON ESSENTIAL FEATURES OF SEMISYNTHETIC ANTIBIOTICS WITH SPECIAL EMPH

1. A COMPREHENSIVE AND AN UPDATE DATABASE ON ESSENTIAL FEATURES OF SEMISYNTHETIC ANTIBIOTICS WITH SPECIAL EMPHASIS ON BIOINFORMATICS September, 2009 *Rajarajan .S , YogambalMuthu , InduPurushothaman , PriyaRoosvelt and Madhan Mohan Coordinator Bioinformatics Infrastructure Facility Center of DBT Govt. of India, New Delhi Presidency CollegeChennai

2. Historical perspective • Extracts of plants and herbs used for centuries to treat illnesses – before we understood that infectious illnesses are caused by microorganisms. • Some of these traditional treatments now known to contain therapeutic drugs – eg quinine in bark from chinchona tree active against the malaria parasites. • 1908 – Paul Ehrlich – salvarsan – arsenic compound –effective treatment of syphilis First systematic approach to find compounds to treat infections • Concept of chemotherapy born - finding a specific chemical compound or drug that kills a microorganism without damaging the host (human) tissues.

3. Sulpha drugs – Domagk – 1930s –sulphanilamide – not used very much now. • Discovery of antibiotics – 1928 – Alexander Fleming– growth of Staphylococcus aureuson an agar plate inhibited by growth of a common blue-green mould (fungus) – Penicilliumnotatum • Florey (Australian) responsible for development of penicillin

4. ANTIBIOTICS • A comprehensive Antibiotic database with an emphasis on Bioinformatics has been developed and updated on March,2008 for free online access • Many pharmaceutical companies are developing semi synthetic form from natural antibiotic and purely synthetic chemicals with antibiotic activity.

5. NEED FOR SEMI-SYNTHETICS ANTIBIOTICS • The reactive beta lactam ring is common to all penicillins and cephalosporin C analogues. • This ring opens during acytelation of the bacterial wall-building enzymes, but previous opening of the ring by acid or beta lactamase destroys antibiotic activity. • Semi synthetic substitutions may protect the ring by steric hindrance;

6. YellapragadaSubbarao • Yellapragada Subbarao (January 12 , 1895 -August 9, 1948) remains in the views of many the most notable medical scientist to emerge from India. • He passed the Intermediate Examination from the Presidency College and entered the Madras Medical College • He discovered the role of Phosphocreatine and Adenosine Triphosphate(ATP) in muscular activity. • Under him Benjamin Duggar made his discovery of Aureomycin in 1945, the world's first tetracycline antibiotic

7. PENICILLIN Penicillin • Penicillin G acid labile, narrow spectrum(mostly active against gram- positive organisms; susceptible to the action of β-lactam (enzyme which splits the β-lactam ring) • Penicillin-V acid stable (a small change in structure gives on important change in properties) can be used orally organism that produce β-lactamases are resistant to Penicillin and Penicillin G Semi-synthetic Penicillin • Ampicillin,Oxacillin,Oxacillin,Cloxacillin,Flucloxacillin,Methicillin,Amoxycillin,Carbenicillin broad spectrum of activity – active against Gram-negative organisms as well as Gram-positive organisms.

8. GENOMIC INFORMATION OF PENICILLIN

9. CEPHALOSPORIN CEPHALOSPORIN-MICROBIAL ORIGIN • Bactericidal antibiotic. Isolated from culture Cephalosporiumacremonium. β-lactam structure is very similar to penicillin. • Treat infections in different parts of the body-the ears, nose, throat, lungs, sinuses, and skin. SEMI-SYNTHETIC CEPHALOSPORIN • Cephalothin,Cephaloridine,Cephaloglycin,Cephalexin,Cephapirin,Cephalexin,Cepharoxadine,Cefaclor,Cefixime active against Gram-negative organisms as well as Gram-positive organisms.

10. GENOMIC INFORMATION ON CEPHALOSPORIN

11. TETERACYCLIN TETERACYCLIN-MICROBIAL ORIGIN • Is a broad-spectrum polyketide antibiotic used against many bacterial infections. Commonly used to treat acne. • It was released by the organism StreptomycesaureofaciensUsed to produce several semi-synthetic derivatives. • Known as the tetracycline antibiotic group. • The general chemical formula is C22H24N2O8. The molecular weight is 444.44 g. SEMI-SYNTHETIC TETERACYCLIN • Methacycline, Doxycycline,Rolitetracyclin • The semi-synthetic, second-generation antibiotic doxycycline became available in 1967. • A number of other naturally occurring and semi-synthetic types of tetracycline are also available. • Each varies somewhat in the organisms it is effective against and in how long a dose remains effective.

12. GENOMIC INFORMATION ON TETRACYCLIN

13. BIOLOGICAL DATABASE-WHY • A biological database is a large, organized body of persistent data, usually associated with computerized software • Designed to update, query, and retrieve components of the data stored within the system. • A simple database might be a single file containing many records, each of which includes the same set of information. • A record associated with a nucleotide sequence database typically contains information such as contact name • The input sequence with a description of the type of molecule • The scientific name of the source organism from which it was isolated

14. APPLICATION OF BIOINFORMATICS IN ANTIBIOTIC RESISTANCE • Scientists examined the genome of Enterococcusfaecalis -a leading cause of bacterial infection among hospital patients. • They have discovered a virulence region made up of a number of antibiotic-resistant genes that contribute to the bacterium's transformation from a harmless gut bacteria to a menacing invader. • The discovery of the region, known as a pathogenicity , which provide useful markers for detecting pathogenic strains and help to establish controls to prevent the spread of infection inwards.

15. SUCCESS OF HUMAN GENOME PROJECT The Human Genome Project provide researchers with powerful tools to understand the genetic factors in human diseases. Paving the way for new strategies for their diagnosis, treatment and prevention. The Human Genome project spurred a revolution in biotechnology innovation around the world. It has already fueled the discovery of genes for more than 1,800 diseases Pharmacogenomics holds the promise that drugs might one day be tailor-made for individuals and suited to each person’s genome

16. Environment, diet, age, lifestyle, and state of health can influence a person's response to, but understanding an individual is thought to be the key to create personalized medicine with highest efficacy and safety. Serious bacterial infections can lead to death in the absence of antibiotic therapy Fungal infection is quite common among poor sections of society due to their occupational conduct in soil: the geriatric population; immunosuppressed patients namely, in organ recipients and in AIDS. Hence the antibiotics remain a necessary weapon in the clinician’s arsenal for ensuring diseases

17. REVIEW OF LITERATURE Antibiotic Resistance Genes Database Received August 14, 2008. Revised September 15, 2008. Accepted September 16, 2008. ARDB can help user to identify mutational resistance for 12 antibiotic target genes by BLAST ARDB contains resistance information for 13293 genes, 377 types, 257 antibiotics, 3369 species and 124 genera. Sorted by: Resistance Type Resistance Gene Antibiotic Resistance Gene(Non RD) Resistance Gene(ALL) Resistance Species Resistance Genus

18. REVIEW OF LITERATURE NOVEL ANTIBIOTIC DATABASE This Data Base includes 5,430 novel substances published in the Journal of Antibiotics Vol.1-56, in 1947-2003. The size of this data base is so large (ca.1,900KB) that it is divided into 5 parts. Sorted by: Substance Name Organism Name Activity Index Affiliation

19. MULTIFUNCTIONAL ANTIMICROBIAL PEPTIDE DATABASE It contains detailedinformation for 525 peptides (498 antibacterial, 155 antifungal,28 antiviral and 18 antitumor) It also provides statisticaldata for a select group of or all the peptides in the database. Peptide information can be searched using keywords such as peptidename, ID, length, net charge, hydrophobic percentage, key residue,unique sequence motif, structure and activity. APD (Antimicrobial Peptide Database ) is a usefultool for studying the structure–function relationshipof antimicrobial peptides.

20. ANTIBIOTIC DATABASE LAUNCHED Doctors may access the latest information on antibiotics and their proper use from a free, peer reviewed database provided on the internet by Johns Hopkins Medical Institutions It offers diagnostic criteria and drug options and is continually updated to reflect the best available information. Emergency alerts, such as drug recalls, will be available immediately Information on more than 160 drugs and more than 140 diseases treated by both specialists and primary care physicians is featured.

21. ANTIBIOTIC RESISTANCE GENES ONLINE (ARGO) • A Database on vancomycin and β­lactam resistance genes • A database containing gene sequences conferring resistance to these two classes of antibiotics. • It is designed as a resource to enhance research on the prevalence and spread of antibiotic resistance genes. • ARGO is the first attempt to compile the resistance gene sequence data with state specific information.

22. None of the already available database have information on bioinformatics of antibiotics. Namely the genomic component of antibiotic or the genomic component of target molecules also. Hence there is a need for some database of a comprehensive, lucid data on antibiotic with specific information of on genome level.

23. Antibiotic Resistance Genes Online (ARGO): • Received  February 14, 2005; revised March 14, 2005; accepted  March 15, 2005; published online March 17, 2005 • Availability :http://www.argodb.org/ • A database containing gene sequences conferring resistance to these two classes of antibiotics. • It is designed as a resource to enhance research on the prevalence and spread of antibiotic resistance genes. • ARGO is the first attempt to compile the resistance gene sequence data with state specific information.

24. LANGUAGES USED HTML(Hyper Text Markup Language) Written by Tim Berners-Lee Is the predominant markup language for Web pages It provides a means to describe the structure of text-based information in a document by denoting certain text as links, headings, paragraphs, lists. HTML is written in the form of tags, surrounded by angle brackets.

25. CSS(CASCADING STYLE SHEET) Written by HåkonWium Lie and Bert Bos Released by Microsoft's Internet Explorer 3 ,1999 A new emerging technology. Is a simple mechanism for adding style (e.g. fonts, colors, spacing) to Web documents

26. DATABASE CONSTRUCTION This antibiotic database was built on the windows Vista operating system In addition to reference books, for specific informations. Antibiotics of microbial origin were collected from the pub - med search using keywords such as, Discoverer, Antibiotic producing organisms, Chemical structure., Dosage, Susceptible organism, Genomic information , Gene responsible , Patent and Industrial production.

27. Introduction, • Effectiveness, • Table information and links • providing detailed information of all the antibiotics of microbial origin. DATABASE DESCRIPTION Themain page of the database contains information about

28. APPLICATION An user- friendly database on antibiotics of semisynthetic has been developed and made available on online in the website semi-synthetic\semihome.html This database is the first of its kind on antibiotics of semisynthetic origin on website, a comprehensive one with the main thrust on bioinformatics This database has been made available for free access by all interested individuals on antibiotics

29. AVAILABILITY This Database on microbial origin has been created, and will be uploaded into the website on 9th September 2009. This is maintained and upgraded by the BIFC center, Presidency College The database will be periodically updated

30. WHO BE WILL BENIFITED Scientists Research Scholars Students

31. Thank you. We invite you to our website www.bifcpresidency.tn.gov.in