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

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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
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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.

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• 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

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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.

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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

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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

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PENICILLIN

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

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GENOMIC INFORMATION OF PENICILLIN
ANTIBIOTIC GENES DATA BASE-LINKS
PENICILLIN pcbAB, pcbC and penDE http//www.bifcpresidency.tn.gov.in/penicillin20main.html
Semi synthetic Penicillin Resistant Gene Gene-Links
AMPICILLIN (ampr) frame.html
CLOXACILLIN bl2d_lcr1,bl2d_moxa bl2d_oxa1,bl2d_oxa10 bl2d_oxa2,bl2d_oxa5 bl2d_oxa9,bl2d_r39 cloxacillinframe.html
METHICILLIN mecr1 methicillinframe.html
CARBENICILLIN bl2c_bro,bl2c_pse1 bl2c_pse3 carbenicillinframe.html
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CEPHALOSPORIN

• CEPHALOSPORIN-MICROBIAL ORIGIN
• Bactericidal antibiotic. Isolated from culture
  Cephalosporiumacremonium. ß-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,Cefi
  xime active against Gram-negative organisms as
  well as Gram-positive organisms.

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GENOMIC INFORMATION ON CEPHALOSPORIN
ANTIBIOTICS GENES DATA BASE-LINKS
CEPHALOSPORIN cefEF-cefG http//www.bifcpresidency.tn.gov.in/cephalosporin2020frame20.html
Semi-Synthetic Cephalosporin Resistant Gene Database-Links
Cephapirin bl2b_tem1, bl2b_tem2, cephapirinframe.html
Cefaclor bl2b_tem1, bl2be_ctxm cefaclorframe.html
cefixime bl2be_ctxm cefiximeframe.html
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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.

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GENOMIC INFORMATION ON TETRACYCLIN
ANTIBIOTICS Resistant Gene DATA BASE-LINKS
Tetracyclin mexa, mexb, oprm, Otra, otrb tetraresi.html
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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

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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.

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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 persons genome

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• 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 clinicians arsenal for ensuring diseases

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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

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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

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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 structurefunction
  relationshipof antimicrobial peptides.

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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.

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ANTIBIOTIC RESISTANCE GENES ONLINE (ARGO)

• A Database on vancomycin and ßlactam 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.

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• 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.

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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.

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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.

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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

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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.

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DATABASE DESCRIPTION

• Themain page of the database contains information
  about

• Introduction,
• Effectiveness,
• Table information and links
• providing detailed information of all the
  antibiotics of microbial origin.

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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

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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

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WHO BE WILL BENIFITED

• Scientists
• Research Scholars
• Students

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