by pharmanotes.org
Post Views: 44
Table of Contents
Antibiotics: Overview and Historical Development
Antibiotics are compounds that inhibit the growth of or kill bacteria and other microbes. Their discovery revolutionized medicine by providing treatments for bacterial infections, reducing mortality and complications. Here’s an overview of the historical development and classification of antibiotics:
- Early Discovery (1900s):
- Paul Ehrlich (1909) discovered Salvarsan, the first chemotherapeutic agent against syphilis.
- Alexander Fleming discovered penicillin in 1928 from Penicillium notatum, which led to its use as the first natural antibiotic.
- Further Developments:
- 1930s-1940s: Streptomycin and tetracycline were discovered from soil bacteria (Streptomyces spp.).
- 1950s-1980s: Synthetic modifications of antibiotics (e.g., cephalosporins, macrolides) were developed to enhance effectiveness and combat resistance.
- Modern Antibiotics: With advancements in biotechnology, synthetic and semi-synthetic antibiotics are developed to target specific pathogens more effectively, reducing side effects and resistance risks.
Antimicrobial Spectrum
The antimicrobial spectrum refers to the range of microorganisms an antibiotic can target. Antibiotics can be classified into:
- Broad-spectrum antibiotics: Effective against a wide range of bacteria (e.g., tetracyclines, ampicillin).
- Narrow-spectrum antibiotics: Effective against specific types of bacteria (e.g., penicillin, vancomycin).
Standardization of Antibiotics
Standardization is crucial to ensure the potency and safety of antibiotics. Common methods include:
- Microbial Assays: Determining minimum inhibitory concentration (MIC) or minimum bactericidal concentration (MBC) against a target microorganism.
- Chemical Assays: Measuring active compounds through titration, chromatography, or spectrometry.
- Biological Assays: Using bioassays to measure antibiotic activity on test organisms.
Screening of Soil for Antibiotic-Producing Organisms
Soil is a primary source for discovering antibiotic-producing microorganisms. The screening process involves:
- Sample Collection and Isolation:
- Soil samples are collected, diluted, and cultured on selective media to isolate microorganisms with antibiotic potential.
- Testing for Antimicrobial Activity:
- The isolated microorganisms are tested against a variety of pathogenic bacteria and fungi to assess their antimicrobial activity.
- Identification of Active Strains:
- Microbes demonstrating significant inhibition zones are further tested and identified as possible antibiotic producers.
Fermentation Process and Design
Fermentation is used to produce antibiotics on a large scale. Key elements include:
- Fermenter Design:
- A fermenter is a bioreactor designed for microbial growth under controlled conditions.
- Essential features include agitators, pH and temperature control, oxygenation systems, and sterilization ports.
- Control of Parameters:
- Temperature, pH, and oxygen levels are optimized to maximize microbial growth and antibiotic production.
- Nutrient supply is maintained to avoid depletion, and waste products are removed periodically.
- Types of Fermentation:
- Submerged Fermentation (SmF): Microbes are grown in a liquid medium, commonly used for large-scale antibiotic production.
- Solid-State Fermentation (SSF): Microbes grow on a solid substrate; often used for secondary metabolites.
Isolation of Mutants and Factors Influencing Mutation Rate
Mutants with enhanced antibiotic production can be isolated through mutation and selection techniques. Common methods include:
- Mutagenesis: Using UV light, chemicals, or radiation to induce mutations in microorganisms.
- Selection: Screening mutated strains for increased antibiotic production or broader antimicrobial spectrum.
- Factors Affecting Mutation Rates:
- Type of mutagen
- Exposure duration and concentration
- Growth phase of the organism
Design of the Fermentation Process
- Inoculum Preparation:
- A pure culture is cultivated in small batches to increase biomass before transferring it to the main fermenter.
- Production Phase:
- Fermentation conditions are optimized for maximum antibiotic yield. Key parameters include maintaining sterility and preventing contamination.
- Harvesting and Downstream Processing:
- After fermentation, the broth is processed to isolate the antibiotic compound.
Isolation and Purification of Fermentation Products
- Penicillin:
- Fermentation: Produced by Penicillium chrysogenum through submerged fermentation.
- Isolation: The culture broth is acidified, filtered, and penicillin is extracted with organic solvents.
- Purification: Penicillin is further purified through crystallization and chromatography.
- Streptomycin:
- Fermentation: Produced by Streptomyces griseus.
- Isolation: Filtration of the fermentation broth followed by adsorption techniques.
- Purification: Streptomycin is precipitated and crystallized for further purity.
- Tetracyclines:
- Fermentation: Produced by Streptomyces aureofaciens and Streptomyces rimosus.
- Isolation: Acid precipitation from fermentation broth and extraction into organic solvents.
- Purification: Further refined using ion-exchange chromatography.
- Vitamin B12:
- Fermentation: Produced by Pseudomonas denitrificans or Propionibacterium.
- Isolation: Vitamin B12 is isolated by centrifugation and precipitation.
- Purification: Purified using chromatography for pharmaceutical use.
Microbial Assays of Antibiotics, Vitamins, and Amino Acids
Microbial assays are bioassays used to determine the potency of antibiotics, vitamins, and amino acids in pharmaceutical preparations:
- Antibiotics: Assays measure the inhibition zone diameter to quantify antibiotic potency.
- Vitamins: Specific bacteria are cultured to measure vitamin requirements.
- Amino Acids: Assays quantify amino acid concentration based on microbial growth rate or metabolic response.
MCQs on Antibiotics
- Who is credited with discovering penicillin?
- A) Louis Pasteur
- B) Alexander Fleming
- C) Robert Koch
- D) Paul Ehrlich
- Answer: B) Alexander Fleming
- The first chemotherapeutic agent discovered to treat syphilis was:
- A) Penicillin
- B) Salvarsan
- C) Streptomycin
- D) Tetracycline
- Answer: B) Salvarsan
- Which of the following is a broad-spectrum antibiotic?
- A) Penicillin G
- B) Tetracycline
- C) Erythromycin
- D) Vancomycin
- Answer: B) Tetracycline
- What does the term “minimum inhibitory concentration (MIC)” refer to?
- A) Minimum drug concentration for therapeutic effect
- B) Lowest concentration inhibiting microbial growth
- C) Minimum dose causing side effects
- D) Maximum dose tolerated by the body
- Answer: B) Lowest concentration inhibiting microbial growth
- Antibiotics that are effective against only a few specific bacteria are termed:
- A) Narrow-spectrum antibiotics
- B) Broad-spectrum antibiotics
- C) Bacteriostatic antibiotics
- D) Bactericidal antibiotics
- Answer: A) Narrow-spectrum antibiotics
- Which is the main source of antibiotics?
- A) Soil microorganisms
- B) Plants
- C) Fungi only
- D) Insects
- Answer: A) Soil microorganisms
- The process of identifying soil organisms that produce antibiotics involves:
- A) Direct extraction of antibiotics
- B) Testing for antimicrobial activity
- C) Chemical synthesis
- D) Genetic manipulation
- Answer: B) Testing for antimicrobial activity
- Which method is used to sterilize fermenters?
- A) Filtration
- B) Chemical agents
- C) Steam under pressure
- D) UV radiation
- Answer: C) Steam under pressure
- The design of a fermenter should include:
- A) Temperature control
- B) pH control
- C) Oxygen supply
- D) All of the above
- Answer: D) All of the above
- Streptomycin was discovered by:
- A) Alexander Fleming
- B) Selman Waksman
- C) Paul Ehrlich
- D) Louis Pasteur
- Answer: B) Selman Waksman
- Which antibiotic is typically isolated from the bacterium Streptomyces griseus?
- A) Penicillin
- B) Streptomycin
- C) Tetracycline
- D) Erythromycin
- Answer: B) Streptomycin
- Which factor most affects the mutation rate in microorganisms?
- A) Temperature
- B) Type of nutrient
- C) Type of mutagen
- D) Amount of water
- Answer: C) Type of mutagen
- Which is a solid-state fermentation process?
- A) Producing yogurt
- B) Brewing beer
- C) Antibiotic production
- D) All of the above
- Answer: C) Antibiotic production
- Which fermentation technique is commonly used for large-scale antibiotic production?
- A) Solid-state fermentation
- B) Submerged fermentation
- C) Open fermentation
- D) Batch fermentation
- Answer: B) Submerged fermentation
- Which antibiotic is known for being effective against a wide range of Gram-positive bacteria?
- A) Vancomycin
- B) Penicillin G
- C) Tetracycline
- D) Cephalexin
- Answer: B) Penicillin G
- During fermentation, the primary purpose of aeration is to:
- A) Control temperature
- B) Prevent contamination
- C) Provide oxygen to aerobic microbes
- D) Remove by-products
- Answer: C) Provide oxygen to aerobic microbes
- What type of fermenter is often used to produce vitamin B12?
- A) Continuous fermenter
- B) Fed-batch fermenter
- C) Solid-state fermenter
- D) None of the above
- Answer: B) Fed-batch fermenter
- Who first observed antibiotic activity in penicillin?
- A) Paul Ehrlich
- B) Robert Koch
- C) Alexander Fleming
- D) Joseph Lister
- Answer: C) Alexander Fleming
- Which antibiotic is known to have bacteriostatic action?
- A) Penicillin
- B) Streptomycin
- C) Tetracycline
- D) Ciprofloxacin
- Answer: C) Tetracycline
- The effectiveness of an antibiotic against a microorganism can be tested by:
- A) Antibiotic resistance testing
- B) MIC and MBC assays
- C) Staining techniques
- D) Genetic sequencing
- Answer: B) MIC and MBC assays
- Antibiotics produced in a fermenter are commonly recovered by:
- A) Centrifugation and extraction
- B) Sedimentation
- C) Precipitation only
- D) Filtration only
- Answer: A) Centrifugation and extraction
- The mutation rate of microbes in fermentation can be increased by:
- A) Increasing pH
- B) Adding mutagens
- C) Reducing temperature
- D) Decreasing nutrients
- Answer: B) Adding mutagens
- In which phase of microbial growth is antibiotic production typically maximized?
- A) Lag phase
- B) Log phase
- C) Stationary phase
- D) Decline phase
- Answer: C) Stationary phase
- Which type of mutation may enhance antibiotic yield in microorganisms?
- A) Silent mutation
- B) Beneficial mutation
- C) Lethal mutation
- D) Neutral mutation
- Answer: B) Beneficial mutation
- Penicillin production requires which type of microorganism?
- A) Escherichia coli
- B) Streptomyces griseus
- C) Penicillium chrysogenum
- D) Aspergillus niger
- Answer: C) Penicillium chrysogenum
- Which of the following is an example of a beta-lactam antibiotic?
- A) Streptomycin
- B) Tetracycline
- C) Penicillin
- D) Chloramphenicol
- Answer: C) Penicillin
- What is the primary target of penicillin in bacterial cells?
- A) Cell membrane
- B) Ribosomes
- C) Cell wall synthesis
- D) DNA replication
- Answer: C) Cell wall synthesis
- Streptomycin primarily targets which bacterial structure?
- A) Cell wall
- B) Ribosomes
- C) DNA
- D) Cytoplasm
- Answer: B) Ribosomes
- In antibiotic standardization, which assay method is commonly used?
- A) MIC determination
- B) Zone of inhibition
- C) Colorimetric assay
- D) Titration
- Answer: B) Zone of inhibition
- What is the function of a stirrer in a fermenter?
- A) Maintain pH balance
- B) Improve nutrient dispersion
- C) Control temperature
- D) Provide sterilization
- Answer: B) Improve nutrient dispersion
- Which antibiotic class does tetracycline belong to?
- A) Aminoglycosides
- B) Beta-lactams
- C) Tetracyclines
- D) Fluoroquinolones
- Answer: C) Tetracyclines
- The term “broad-spectrum antibiotic” refers to drugs effective against:
- A) Only Gram-positive bacteria
- B) Only Gram-negative bacteria
- C) A wide range of bacteria
- D) Viruses and bacteria
- Answer: C) A wide range of bacteria
- Which of the following is an aminoglycoside antibiotic?
- A) Vancomycin
- B) Penicillin
- C) Erythromycin
- D) Streptomycin
- Answer: D) Streptomycin
- An antibiotic produced by Streptomyces venezuelae is:
- A) Penicillin
- B) Tetracycline
- C) Chloramphenicol
- D) Erythromycin
- Answer: C) Chloramphenicol
- What is the main byproduct of penicillin fermentation?
- A) CO₂
- B) Alcohol
- C) Lactic acid
- D) Ammonia
- Answer: A) CO₂
- Which step is crucial for isolating antibiotics after fermentation?
- A) Filtration
- B) Sedimentation
- C) Centrifugation
- D) Crystallization
- Answer: C) Centrifugation
- The primary antibiotic used to treat tuberculosis is:
- A) Tetracycline
- B) Rifampin
- C) Penicillin
- D) Erythromycin
- Answer: B) Rifampin
- For what purpose is the shake flask method used in antibiotic production?
- A) Small-scale antibiotic production
- B) Large-scale antibiotic production
- C) Antibiotic purity testing
- D) Genetic modification
- Answer: A) Small-scale antibiotic production
- Which instrument is commonly used to measure cell density in fermentation?
- A) Spectrophotometer
- B) Microscope
- C) Autoclave
- D) Refractometer
- Answer: A) Spectrophotometer
- The primary microorganism used in the production of vitamin B12 is:
- A) E. coli
- B) Streptomyces griseus
- C) Pseudomonas denitrificans
- D) Saccharomyces cerevisiae
- Answer: C) Pseudomonas denitrificans
- In antibiotic production, which phase involves rapid cell division?
- A) Lag phase
- B) Log phase
- C) Stationary phase
- D) Decline phase
- Answer: B) Log phase
- The purpose of a chemostat in fermentation is to:
- A) Maintain continuous culture conditions
- B) Sterilize the medium
- C) Add mutagens to the culture
- D) Reduce temperature
- Answer: A) Maintain continuous culture conditions
- Which antibiotic is primarily obtained from Penicillium notatum?
- A) Vancomycin
- B) Streptomycin
- C) Penicillin
- D) Erythromycin
- Answer: C) Penicillin
- What is the purpose of adding a surfactant in the fermentation medium?
- A) Increase cell density
- B) Decrease viscosity
- C) Enhance oxygen transfer
- D) Prevent contamination
- Answer: C) Enhance oxygen transfer
- An antibiotic with bactericidal action will:
- A) Stop bacterial growth
- B) Stimulate bacterial growth
- C) Kill bacteria
- D) Promote bacterial spore formation
- Answer: C) Kill bacteria
- Which process is used to identify mutations in antibiotic-producing strains?
- A) MIC testing
- B) Replica plating
- C) Titration
- D) Gram staining
- Answer: B) Replica plating
- Antibiotic resistance can result from:
- A) Overuse of antibiotics
- B) Mutation in bacteria
- C) Natural selection
- D) All of the above
- Answer: D) All of the above
- A common impurity in antibiotics is:
- A) Fungal spores
- B) Bacterial endotoxins
- C) Excess glucose
- D) Sodium chloride
- Answer: B) Bacterial endotoxins
- What is the purpose of pH control in antibiotic fermentation?
- A) Enhance microbial growth
- B) Ensure product stability
- C) Prevent contamination
- D) Both A and B
- Answer: D) Both A and B
- Antibiotic activity against Gram-negative bacteria is commonly tested using:
- A) E. coli
- B) Staphylococcus aureus
- C) Bacillus subtilis
- D) Mycobacterium tuberculosis
- Answer: A) E. coli
- A fermenter is typically equipped with a sparger to provide:
- A) Oxygen
- B) Nitrogen
- C) Carbon dioxide
- D) None of the above
- Answer: A) Oxygen
- Which enzyme class is often targeted by beta-lactam antibiotics?
- A) Polymerases
- B) Proteases
- C) Transpeptidases
- D) Kinases
- Answer: C) Transpeptidases
- The term “antimicrobial spectrum” refers to:
- A) Range of effectiveness against microbes
- B) Chemical composition
- C) Microbial classification
- D) Side effects
- Answer: A) Range of effectiveness against microbes
- Which test is used to measure antibiotic potency?
- A) Disc diffusion assay
- B) Gram staining
- C) PCR
- D) Fermentation
- Answer: A) Disc diffusion assay
- An antibiotic that binds to the 50S subunit of bacterial ribosomes is:
- A) Tetracycline
- B) Streptomycin
- C) Erythromycin
- D) Vancomycin
- Answer: C) Erythromycin
- Tetracyclines are commonly derived from:
- A) Penicillium chrysogenum
- B) Aspergillus fumigatus
- C) Streptomyces rimosus
- D) Saccharomyces cerevisiae
- Answer: C) Streptomyces rimosus
- Vitamin B12 production involves which type of fermentation process?
- A) Anaerobic
- B) Aerobic
- C) Both A and B
- D) None
- Answer: B) Aerobic
- Mutants with enhanced antibiotic productivity are often obtained by:
- A) UV irradiation
- B) Freezing
- C) Increasing temperature
- D) Fermentation scaling
- Answer: A) UV irradiation
- Penicillin belongs to which group of antibiotics?
- A) Aminoglycosides
- B) Tetracyclines
- C) Macrolides
- D) Beta-lactams
- Answer: D) Beta-lactams
Also, Visit:
B. Pharma Previous Year Question Paper
B. Pharma 8th Semester Previous Year Question Paper
D. Pharma Notes