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Antibiotics in biotechnology

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Alison Moore

on 3 April 2013

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Transcript of Antibiotics in biotechnology

What are antibiotics? Antibiotics History of antibiotics Late 1800s Production of antibiotics Living sources Antibiotic (from the Ancient Greek: – anti, "against", and – bios, "life")
Substance produced by a microorganism
Kills or inhibits the growth of other microorganisms, namely bacteria
Are antimicrobials (group includes anti-viral, anti-fungal, anti-parasitic drugs)
Relatively harmless to the host, therefore can treat infection Nobel Prizes Industrial production Upstream processing Downstream processing Uses of antibiotics Administration Physiology Bacteria
Bacillus brevis
B. polymyxa
Steptococcus cremoris
Actinomycetes
Micromonospora purpurea
Nocardia mediterranei
Streptomyces griseus
Fungi
Cephalosporium acremonium
Penicillium chrysogenum
P. griseofulyum Development with biotechnology •Originally only derived from living organisms
Most new ones are semi-synthetic
Chloromycetin, cycloserine, and synthetic tetracycline were first produced completely by man
•Use new tools to culture on large scale (fermentation)
•New strains improve production and reduce costs
•Aim to make more specific to bacteria with fewer side effects Uses any technology that leads to synthesis of product
Production strains stored in dormant form
Incubated and fermented with oxygen to grow
Uses carbon, nitrogen, and mineral sources in penicillin production Inoculum seeded in fermenter
Temperature, pH, and mineral contents controlled
Incubated with oxygen to grow
Antibiotic produced over time Fermentation Extraction and purification of biotechnological product from fermentation
Stages:
Solid-liquid separation
Extraction
Filtration, rotary vacuum filter
Add to low pH solution
Purification
Charcoal treatment
Sterilization
Crystallization
Packaging:
Sterile vials as powder or suspension
Tabletted with film coating The type of administration affects the absorption rate of the drug
Parentally (intravenously, intra-muscularly…)
Quickest absorption, more serious cases
IV less painful, less irritating, higher dose
Orally (tablets or caplets)
Local application to skin, mucous membranes, respiratory tract…
Inhalation as aerosol (small molecules sprayed in respiratory passages) Metabolized by:
Kidneys (most important)
Also excreted through faeces, sweat, and respiration Prevent microorganisms/bacteria from making peptidoglycan for cell wall Inhibit protein synthesis machinery (eg. Tetracyclines, chloramphenicol, aminoglycosides, and macrolides) Disrupt integrity/structure of cell membranes, killing them (eg. Polymyxins)
Effective on Gram-negative bacteria that have definite cell membrane Some bind to the proteins required for processing of DNA and RNA, stopping synthesis, and growth of cells (eg. Quinolones, rifamycins) Anti-metabolites/growth factor analogs
Competitively inhibit the important metabolic pathways in bacterial cell (eg. Gantrisin, Trimethoprim) Cell wall synthesis inhibitors Interfering with protein synthesis Cell membrane inhibitors Effect on Nucleic Acids Competitive inhibitors Applications/uses Streptomycin effective against diseases that penicillin was not (eg. Bubonic plague)
Aureomycin does work of both penicillin and streptomycin
Terramycin considered one of most effective antibiotics ever found
Chloromycetin effective against typhus, whooping cough, and typhoid
Fluoroquinolone used on chickens and turkeys to stop E. coli deaths
Clinically used in ophthalmology Antibiotic resistance Evolutionary process based on natural selection
Newer strains of bacteria resistant to previously lethal antibiotics
Antibiotics act as selective pressure on bacteria
Those that survive are selected for, and go on to reproduce
Instrinsic resistance can occur naturally from genetic makeup
Mutations also aid survivorship
Cross-resistance with other bacteria lead to co-resistance of many antibiotics Genetically Strains Solutions Development of pharmaceutical compounds that reverse antibiotic resistances
Called “resistance modifying agents”
Idea of using bacteriophages instead of antibiotics
Phages tailored to specific bacteria, to destroy them Classes Broad-spectrum can act against a wide range of bacteria
Acts on both Gram-positive and Gram-negative bacteria
Narrow-spectrum are only each effective against one specific family of bacteria Germ theory accepted (bacteria as cause of ailments)
The search for antibiotics began
Scientists began to devote time to searching for drugs to kill the disease-causing bacteria
German doctors, Rudolf Emmerich and Oscar Low
First to make an effective medication that they called pyocyanase from microbes
First antibiotic to be used in hospitals, however not often work The 1940s Manufacturing process for Penicillin G Procaine invented by Howard Florey and Ernst Chain
Penicillin could now be sold as a drug
American microbiologist Selman Waksman made streptomycin from soil bacteria
The first of a new class of drugs called aminoglycosides
Streptomycin could treat diseases like tuberculosis, but with severe side effects 1928 and Penicillin The first effective antibiotic discovered
French physician Ernest Duchesne noted in his 1896 thesis that certain Penicillium molds killed bacteria
Sir Alexander Fleming's bacterium culture of Staphylococcus aureus was ruined by accidental fungal contamination
Fleming noticed a clear zone surrounding the colony of mold (Penicillium notatum)
Mold was secreting something that stopped bacterial growth
Since the mold was of the genus Penicillium, he named this compound penicillin The 1950s 1955: Tetracycline patented by Lloyd Conover
Became the most prescribed broad spectrum antibiotic in the United States
1957: Nystatin patented and used to cure disfiguring and disabling fungal infections 1981 SmithKline Beecham patented Amoxicillin (amoxicillin/clavulanate potassium tablets)
First sold the antibiotic in 1998 under the tradenames: Amoxicillin, Amoxil, and Trimox
Amoxicillin is a semi synthetic antibiotic 1939: Edward Chain and Howard Florey further studied penicillin
Later carried out human trials
Fleming, Florey, and Chain shared the 1945 Nobel Prize for medicine for their work on penicillin
Ushered in the era of antibiotics Antibiotic use in foods has led to creation of antibiotic-resistant strains
Salmonella spp.
Campulobacter spp.
Escherichia coli
Enterococcus spp.
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