BacT lecture 4 Flashcards
What is an antibiotic?
eg. gentamicin, streptomycin
A chemical substance produced by a *microorganism that inhibits the growth of or kills other microorganism
A chemical substance derived form a biological source or produced by chemical synthesis that kills or inhibits the growth of microorganisms
Antimicrobial agent
eg sulfonamide, enrofloxacin
When do we use antibiotics or antimicrobial agents?
When body’s normal defenses cannot prevent or overcome disease
Must act with in the host without damaging the host
Disinfectants and antiseptics act outside the body of the host
Who and how was penicillin discovered?
Alexander Fleming- It was an accident
Sources of Chemotherapeutic Antimicrobial Agents
Natural (true antibiotics)
Semi-synthetic
Synthetic
Where do Natural Antimicrobial Agents come from?
Fungal and bacterial
benzyl penicillin, gentamicin, streptomycin, chlortetracycline
Streptomyces, Bacillus, Penicillium
What are Semi-synthetic Antimicrobial Agents?
Chemically-altered natural compound
ampicillin, amikacin
What are Synthetic Antimicrobial Agents?
Chemically designed in the lab
sulfonamide, enrofloxacin, marbofloxacin
What are the classification of antimicrobial agents?
Chemical family structure
Mode of action
Type of antimicrobial activity
Spectrum of antibacterial activity
Draw the distinguishing characteristic of Beta Lactams
Refer to slide 8 of lecture 4 BacT
Mode of action (functional groups)
Inhibitors of cell was synthesis Inhibitors of protein synthesis Inhibitors of nucleic acid synthesis Inhibitors of membrane function Anti-metabolites
Cell wall synthesis inhibitors
Beta lactam antibiotics
Penicillin, ampicillin, cephalosporins, carbapenem, monobactam
What do cell wall synthesis inhibitors beta lactam antibiotics work?
Inhibit peptidoglycan synthesis
Bind and inhibit a group of proteins called penicillin binding proteins
What is an enzyme present in bacteria which can cleave beta lactam ring and inactivate penicillin and contribute to resistance?
Beta Lactamase
Clauvulanic acid does what?
(suicide substrate) prevent degradation of penicillin by beta lactamase
Cell wall synthesis inhibitors Glycopeptides
Vancromycin, daptomycin
Last drugs of choice for some gram-pos bacteria
V resistance - increasing
Protein Synthesis inhibitors
Aminoglycosides Tetracyclins Macrolides Phenocols Lincosamides
Antibiotic examples of Aminoglycosides and which protein subunit do they inhibit?
Gentamicin, amikacin, kanamycin, streptpmycin
30s subunit
Antibiotic examples of Tetracyclins and which protein subunit do they inhibit?
Oxytetracycline, chlortetracycline
30s subunit
Antibiotic examples of Macrolides and which protein subunit do they inhibit?
Erythromycin, azithromycin
50s subunit
Antibiotic examples of Phenocols and which protein subunit do they inhibit?
Chloramphenicol
50s subunit
Antibiotic examples of Lincosamides and which protein subunit do they inhibit?
Clindamycin
50s subunit
DNA synthesis inhibitors
Quinolones
Metronidazole
Examples if quinolone and what do they do?
Nalidixic acid, ciprofloxacin
*Inhibit enzyme DNA gyrase
What is the resistance of quinolones due to?
A mutation in the gene for enzyme DNA gyrase
What does metronidazole?
Makes breaks in the DNA
What are the RNA synthesis inhibitors?
Rifampin
Mupirocin
What does rifampin do?
Inhibit RNA polmerase (transcription)
Active against Mycobacterium tuberculosis
Extremely multidrug resistance TB
What does mupirocin do?
Inhibit tRNA synthetase (translation)
Commonly used for MRSA
What are the folic acid synthesis inhibitors and what do they do?
(antimetabolites)
Sulfonomides
Trimethoprim
Competitive inhibitors of dihydrofolate reductase
Types of antimicrobial activity. What is Bacteriostatic Activity?
Inhibition of bacterial multiplication/growth
Visual inhibition of bacterial growth is the basis of routine susceptibility testing
In a drug dilution series, the lowest drug concentration that completely *inhibits bacterial growth is?
Minimal Inhibitory Concentration (MIC)
In a drug dilution series, the lowest drug concentration that *kills the bacterial population is?
Minimal Bactericidal Concentration (MIB)
Broad vs Narrow spectrum antibiotics
Broad spectrum active against a wide variety of bacteria (Tetracycline)
Narrow spectrum only work on a select few bacteria (Penicillin)
How do you know certain bacteria is susceptible to a particular antibacterial?
Antibacterial Susceptibility Testing; either Dilution or Diffusion
Disk Diffusion (Kirby Bauer testing)
Single- concentration disk
Growth inhibition zone diameter measured
Use published reference break points to interpret results
Broth Dilution
One to multiple dilutions of antibiotic
Measure and report growth inhibition endpoint (MIC)
Use published references breakpoints to interpret
Susceptible, Intermediate, Resistant
Susceptibility Results
S- High likelihood of therapeutic success
I- Uncertain therapeutic outcome
R- High likelihood of therapeutic failure
In MRSA and Pseudomonas aeruginosa, targeting quorum sensing provides for
Regulatory control over genes
4 types of horizontal gene transfer
Lysogenic conversion (transduction)
Transduction (generalized transduction)
Conjugation
Transformation
Lysogenic conversion (transduction)
Bacterphage DNA into a bacteria cell
Transduction (generalized transduction)
bacterial DNA into another bacteria via virus
Conjugation
Plasmids
Transformation
Uptake of exogenous DNA
Mobile genetic elements
Insertion sequences
Transposons
Types of resistance
Innate - preexisting genomic property
Acquired - new genetically encoded trait not representative of the species (acquired by mutation or horizontal gene transfer
Mechanisms of resistance
Enzymatic destruction or inactivation of drug
Prevention of penetration to target sites within microbe
Alteration of drugs target site
Rapid efflux of antibiotics
Consequences of antimicrobial resistance
Increased mortality to infectious disease
Increased nosocomial infections
High treatment costs
Decreased development of new drugs
Almost all bacterial are acquiring resistance to antibacterial because
Widespread antimicrobial use Microbial adaptation and change Change in demographics Medical advances Change in ecosystems Cutbacks in public health systems and surveillance
