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Control of Microbial Growth
Tim HoUniversity of Alberta, Canada* The materials are mostly based on Dr. Brian Lanoil’s Microb 265
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Part II
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Objectives
1. Know 3 methods of microbial control
2. Know the strategies on how drugs control the growth of microorganisms.
3. Understand how do bacteria become resistant to antibiotics.
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• Physical agents• Mechanical removal methods• Chemical agents
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1. With minimal side effects2. Therapeutic dose: the amount of drug required for treatment or the
desired effect. 3. Broad spectrum activity: against a wide variety of pathogens or do
not know the specific bacteria that want to target.4. Chemotherapeutic agents can be synthetic or semi-synthetic.
Characteristics of antimicrobial drugs:
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Dilution Susceptibility test• Each test tube containing different concentrations of drug - MIC: minimum inhibitory concentration - MLC: minimum lethal concentration
Low [drug] high [drug]
+ + + + + + + - - -
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Image:http://www.biotopics.co.uk/microbes/penici.html
Disk diffusion test• Kirby-Bauer method• Drug diffuses from disk into agar, establishing concentration
gradient• Measure the diameter of clear zone (no growth) around disks -
> determine MIC and MLC
Large clear zone = sensitive
No or small clear zone = resistant
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Disk diffusion test
Image:http://www.biotopics.co.uk/microbes/penici.html
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How different types of antibiotics affect cell functions
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Folic acid synthesis inhibitors
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Folic acid synthesis inhibitors
Sulfanilamide:
- Competitive inhibitor of PABA
- [PABA] ↑= rate of folic acid biosynthesis ↓
Image: Fdardel, 2011
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DNA gyrase inhibitors
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DNA gyrase inhibitors
Quinolones:
- inhibit bacterial DNA gyrase
- effective against G- urinary tract infections and respiratory infections
- (eg. Bacillus anthracis)
- [PABA] ↑= rate of folic acid biosynthesis ↓tim
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Image: Drug Reference - Encyclopedia
Ciprofloxacin
DNA gyrase: the enzyme that introduces negative supercoils into DNA
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RNA synthesis inhibitors
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RNA synthesis inhibitors
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Rifamycin/ Rifampin:
- block transcription by binding RNA polymerase
- Not selectively toxic → Prokaryotes and eukaryotes synthesize nucleic acids in pretty much the same way
- [PABA] ↑= rate of folic acid biosynthesis ↓
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Cell wall synthesis inhibitors
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- Ampicillin is protected from lactamases by co-treatment with clavulanic acid
WHY: ß-lactamases have higher binding affinity for clavulanic acid than ampicillin
Image: Dengler et al. BMC Microbiology 2011 11:16 doi:10.1186/1471-2180-11-16
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Cell wall synthesis inhibitors
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Image: Insilico Genomics Lab Technologies. http://insilicogenomics.in/penicillin.asp
It breaks ß-lactam rings: antibiotic resistance - G+ cells: ß-lactamases are located on outside surface
Activity is blocked by binding to transpeptidases
G- cells: ß-lactamases are in periplasmic space
(transpeptidase)
G + bacteria are more susceptible to ß-lactam antibiotics!!
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blocks transpeptidization
blocks dephosphorylation of bactoprenol phosphate
blocks D-Ala peptidization
Cell wall synthesis inhibitors
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Image: Dengler et al. BMC Microbiology 2011 11:16 doi:10.1186/1471-2180-11-16
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Protein synthesis inhibitors
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Protein synthesis inhibitors
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Aminoglycosides: - Binding to the small subunit
ribosome- effective against G- cells
Macrolides:- Binding to the large
subunit ribosome
Tetracyclines:- First broad-spectrum antibiotics- Blocking tRNA attachment to
ribosome- effective against G- and G+
cells
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Cytoplasmic membrane inhibitors
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Cytoplasmic membrane inhibitors
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Daptomycin:
- Cyclic lipopeptide
- Makes pore on cytoplasmic membrane
- Resistance from changes in cell membrane structure
- Primarily targets G+ cells (G- cells have extra outer membrane: protection)
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Anti-fungal Drugs• Fungal infections are difficult to treat - host and pathogen have biological similarity → drug can harm host at the same time• Target against chitin (fungal cell wall) mostly - animals (host) don’t have chitin• Nystatin: first discovered antifungal antibiotic in 1949 by Hazen and
Brown• Superficial mycoses - Infections of outer layers of skin - Treatment (drugs): Miconazole, Nystatin, and Griseofulvin - Minimizes toxic systemic side effects (e.g. liver damage)
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Antiviral Drugs
• Many drugs are still in development stage• Mainly target against either RNA or DNA synthesis of viral
pathogen - Structural analogs of purine or pyrimidine bases - difficulties: viruses use metabolic machinery of the host• Protease inhibitors: against virus-specific enzymes• Interferons: stimulate production of host anti-viral proteins