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MICRO LAB Quiz Chapter 12
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1Chemical compounds to kill or suppress microorganisms
[blank_start]Antimicrobial agents[blank_end]- AAntimicrobial agents
2Natural, semisynthetic, or synthetic molecules used to treat or prevent disease
[blank_start]Antibiotics[blank_end]- AAntibiotics
3Key steps for antimicrobial agent to inhibit/kill microorganism:
Must be in active form
[blank_start]Pharmacodynamics[blank_end]- APharmacodynamics
4• Key steps for antimicrobial agent to inhibit/kill microorganism:
Must be able to achieve sufficient levels or concen-trations at site of infection
[blank_start]Pharmacokinetics[blank_end]- APharmacokinetics
5• Inhibit bacterial growth but do not kill the organism
[blank_start]Bacteriostatic agents[blank_end]- ABacteriostatic agents
6Mode of Action of Antibacterial Agents
• Inhibitors of cell wall synthesis
1. [blank_start]Beta-lactams[blank_end]
2. [blank_start]Glycopeptides[blank_end]- ABeta-lactams
- BGlycopeptides
7Mode of Action of Antibacterial Agents
• Inhibitors of Folic Acid Synthesis
1. [blank_start]Sulfonamides[blank_end]
2. [blank_start]Trimethoprim[blank_end]- ASulfonamides
- BTrimethoprim
8Mode of Action of Antibacterial Agents
• Inhibitors of DNA & RNA synthesis
1. [blank_start]Fluoroquinolone[blank_end]
2. [blank_start]Ciprofloxacin[blank_end]
3. [blank_start]Metronidazole[blank_end]
4. [blank_start]Rifampin[blank_end]- AFluoroquinolone
- BCiprofloxacin
- CMetronidazole
- DRifampin
9Inhibitors of Protein Synthesis
• Binds to 30S
[blank_start]Aminoglycosides[blank_end]
[blank_start]Tetracyclines[blank_end]
[blank_start]Glycylcyclines[blank_end]- AAminoglycosides
- BTetracyclines
- CGlycylcyclines
10Inhibitors of Protein Synthesis
• Binds to 50S
[blank_start]Macrolide-Lincosamide-Streptogramin[blank_end]
[blank_start]Oxazolidinone[blank_end]
[blank_start]Chloramphenicol[blank_end]- AMacrolide-Lincosamide-Streptogramin
- BOxazolidinone
- CChloramphenicol
11Mode of Action of Antibacterial Agents
• Inhibitors of Cell Membrane functions
[blank_start]Lipopeptides[blank_end]
[blank_start]Polymixins[blank_end]- ALipopeptides
- BPolymixins
12Murein other name: [blank_start]Peptidoglycan[blank_end]
- APeptidoglycan
13• Peptidoglycan/murein production
1. Synthesis of precursors in the cytoplasm
2. Transport of lipid-bound precursors across the cytoplasmic membrane
3. Insertion of glycan units into the cell wall
4. Transpeptidation linking and maturation
• [blank_start]D-cycloserine[blank_end] and [blank_start]bacitracin[blank_end] inhibit steps 1 and 2
• [blank_start]Beta-lactams[blank_end] and [blank_start]glycopeptides[blank_end] inhibit steps 3 and 4- AD-cycloserine
- Bbacitracin
- CBeta-lactams
- Dglycopeptides
14Beta-lactam
•Binds [blank_start]enzymes[blank_end] involved in [blank_start]peptidoglycan[blank_end] production
•[blank_start]Penicillin-binding proteins[blank_end] (PBPs)
•[blank_start]Transpeptidase-transglycosylase[blank_end] enzymes
•Mediate [blank_start]peptidoglycan cross-linking[blank_end]
•Natural and semisynthetic- Aenzymes
- Bpeptidoglycan
- CPenicillin-binding proteins
- DTranspeptidase-transglycosylase
- Epeptidoglycan cross-linking
15[blank_start]Beta-lactam ring[blank_end]
• Similar to [blank_start]acyl-D-alanyl-D-alanine[blank_end]
• Normal substrate for synthesis of linear glycopeptide in the bacteri-al cell wall
• Must pass through cell wall [blank_start]porins[blank_end] in gram-negative cells to reach cell PBPs
• Binding of the type of B-lactam to specific PBPs
• Influences effectiveness of certain drugs on specific organisms
• For Gram-positive and Gram-negative- Aacyl-D-alanyl-D-alanine
- Bporins
- CBeta-lactam ring
16[blank_start]Glycopeptides[blank_end]
• Binds to the terminal D-Ala-D-Ala of the [blank_start]pentapeptidyl-glycosyl peptidoglycan[blank_end] intermediates
• Bind to the [blank_start]substrate[blank_end] of the transpeptidation enzyme
• Blocks the [blank_start]transpeptidation step[blank_end] in cell wall biosynthesis
• [blank_start]Vancomycin[blank_end], [blank_start]dalbavancin teicoplanin[blank_end], [blank_start]oritavancin[blank_end] and [blank_start]telavancin[blank_end]
• Mainly for Gram-positive- AGlycopeptides
- Bpentapeptidyl-glycosyl peptidoglycan
- Csubstrate
- Dtranspeptidation step
- EVancomycin
- Fdalbavancin teicoplanin
- Goritavancin
- Htelavancin
17Inhibition of Folate Synthesis
Folic acid pathway
•Provides precursor molecules needed in DNA syn-thesis
•Combined antibiotic: SXT
(SXT = [blank_start]Sulfamethoxazole[blank_end] + [blank_start]Trimethoprim[blank_end])
•For [blank_start]enterobacter[blank_end]-caused UTI
Sulfonamides
•Binds [blank_start]dihydropteroate synthase[blank_end]
•[blank_start]Sulfamethoxazole[blank_end] (SMZ)
[blank_start]Trimethoprim[blank_end] (TMP)
•Binds [blank_start]dihydrofolate reductase[blank_end]- ASulfamethoxazole
- BTrimethoprim
- Centerobacter
- DSulfamethoxazole
- ETrimethoprim
- Fdihydropteroate synthase
- Gdihydrofolate reductase
18Interference with DNA Replication
• Enzymes involved in DNA replication
• Topoisomerase [blank_start]1[blank_end], [blank_start]2[blank_end], [blank_start]3[blank_end] and [blank_start]4[blank_end] (numbers)- A4
- B3
- C2
- D1
19Interference with DNA Replication
Quinolones/[blank_start]Fluoroquinolones[blank_end]
• Gram([blank_start]+[blank_end]): Targets topoisomerase II ([blank_start]DNA gyrase[blank_end])
• Gram([blank_start]-[blank_end]): Targets topoisomerase IV
• New generations can target both enzymes- A+
- B-
- CFluoroquinolones
- DDNA gyrase
20Interference with DNA Transcription
• Rifampin
• Synthetic derivative of [blank_start]rifamycin B[blank_end]
• Targets [blank_start]RNA polymerase B[blank_end] subunit at an allosteric site
• Also blocks RNA chain elongation- ARNA polymerase B
- Brifamycin B
21Interference of mRNA Translation
• Inhibits protein synthesis
• Binds to 30S or 50S ribosomal subunits
[blank_start]30S[blank_end] ribosomal subunit:
• aminoglycosides, spectinomycin, tetracyclines, glycylcyclines
[blank_start]50S[blank_end] ribosomal subunit:
• macrolides, lincosamides, streptogramins, chloramphenicol,
oxazolidinones, ketolides- A30S
- B50S
22Interference of mRNA Translation
[blank_start]Aminoglycosides[blank_end]
• Results in mistranslation and subsequent production of
aberrant proteins
• Promotes cell leakage and enhance penetration
of other antibiotics- AAminoglycosides
23Interference of mRNA Translation
[blank_start]Spectinomycin[blank_end]
• Interferes with the stability of peptidyl tRNA binding to the
ribosome
• Does not cause mistranslation- ASpectinomycin
24Interference of mRNA Translation
[blank_start]Tetracycline[blank_end]
• Tetracylcin, doxycycline, and minocycline
• Results in the premature release of tRNA and termination
of peptide bond formation
Toxicity
• Upper gastrointestinal effects
• Cutaneous phototoxicity
• Photoallergic immune reaction- ATetracycline
25Interference of mRNA Translation
[blank_start]Macrolides[blank_end]
• erythromycin, clarithromycin, and azithromycin
• allow initiation and mRNA translation to being but act by
inhibiting peptide elongation- AMacrolides
26Interference of mRNA Translation
[blank_start]Ketolides[blank_end]
• [blank_start]Telithromycin[blank_end]
• Bypass macrolide-resistant mechanisms by improving ribosome
binding affinity- AKetolides
- BTelithromycin
27Interference of mRNA Translation
[blank_start]Oxazolidinones[blank_end]
• [blank_start]Linezolid[blank_end]
• For Gram (+): MRSA, VRE, S. pneumoniae, M. tuberculosis
• Blocks the initiation step and translocation of peptidyltRNA
MRSA = [blank_start]Methicillin[blank_end]-[blank_start]resistant[blank_end] [blank_start]Staphylococcus[blank_end] [blank_start]aureus[blank_end]
VRE = [blank_start]Vancomycin[blank_end]-[blank_start]Resistant[blank_end] [blank_start]Enterococci[blank_end]- AOxazolidinones
- BLinezolid
- CMethicillin
- Dresistant
- EStaphylococcus
- Faureus
- GVancomycin
- HResistant
- IEnterococci
28Interference of mRNA Translation
[blank_start]Streptogramin[blank_end]
• [blank_start]70[blank_end]:[blank_start]30[blank_end] mixture of A and B molecules called [blank_start]Dalfopristinquinupristin[blank_end]
• Disrupt translation by blocking elongation and binding of
aminoacyl-tRNA- ADalfopristinquinupristin
- BStreptogramin
- C70
- D30
29Interference of mRNA Translation
[blank_start]Glycylcycline[blank_end]
• [blank_start]Tigecycline[blank_end]
• Higher affinity for [blank_start]30S[blank_end] ribosomal subunit than tetracycline
• Increased effectiveness against tetracycline-resistant organisms
• Wide spectrum of activity agains gram-positive, gramnegative
and atypical pathogens- A30S
- BTigecycline
- CGlycylcycline
30Mechanisms of Antibiotic Resistance
Some resistance is 2000 years old
• [blank_start]Canadian glaciers[blank_end]
Some resistance in deep sea areas is 10,000 years old
• [blank_start]Near Papua New Guinea[blank_end]
Evolution of resistance
• May have occurred as a way to prevent autotoxicity- ACanadian glaciers
- BNear Papua New Guinea
31Mechanisms of Antibiotic Resistance
Resistance
[blank_start]Intrinsic[blank_end] resistance
• Naturally found in bacteria (chromosomal)
[blank_start]Acquired[blank_end] resistance
• Acquired from exogenous DNA (plasmid or through [blank_start]conjugation[blank_end])- AIntrinsic
- BAcquired
- Cconjugation
32Intrinsic Antibiotic Resistance
1. [blank_start]Impermeability[blank_end]
2. [blank_start]Biofilms[blank_end]
3. [blank_start]Efflux[blank_end]
4. [blank_start]Enzyme Inactivation[blank_end]- AImpermeability
- BBiofilms
- CEfflux
- DEnzyme Inactivation
33Intrinsic Antibiotic Resistance
[blank_start]Impermeability[blank_end]
• Influx through cell wall depends on:
• Chemical nature of drug
• Structural characteristics of cell wall
Examples:
Intrinsic resistance to vancomycin
• Gram(-): impermeable to VA
• [blank_start]Lactobacillus[blank_end] and [blank_start]Leuconostoc[blank_end]: lack precursor
target for VA to bind in cell wall
Intrinsic resistance to penicillin
• [blank_start]Enterococcus faecalis[blank_end] and [blank_start]Enterococcus faecium[blank_end]: their
PBPs have low affinity to penicillins- AImpermeability
- BLactobacillus
- CLeuconostoc
- DEnterococcus faecalis
- EEnterococcus faecium
34Intrinsic Antibiotic Resistance
[blank_start]Biofilms[blank_end]
• Sessile bacterial communities that are irreversibly attached to a
solid surface and are embedded in an exopolysaccharide matrix
• Highly resistant to antibiotic exposure
Resistance mechanisms
• Multifactorial; cell-cell chemical communication which
varies from organism to organism
• Not attributed to typically acquired genetic mechanisms
• Determined by chemical and physical characteristics of
biofilm formation- ABiofilms
35Intrinsic Antibiotic Resistance
Efflux
• Efflux pumps
• Transporter proteins for the extrusion of toxic substances
and antibiotics
• Increase secretion of drug
Classified into Superfamilies:
• [blank_start]Major facilitator[blank_end] (MFS)
• [blank_start]Resistance nodulation cell division[blank_end] (RND)
• [blank_start]Small multidrug resistance family[blank_end] (SMR)
• [blank_start]Adenosine triphosphate[blank_end] (ATP)-[blank_start]binding cassette[blank_end] (ABC)
• [blank_start]Multidrug and toxic effects[blank_end] (MATE)- AMajor facilitator
- BResistance nodulation cell division
- CSmall multidrug resistance family
- DAdenosine triphosphate
- Ebinding cassette
- FMultidrug and toxic effects
36Intrinsic Antibiotic Resistance
Enzyme Inactivation
• Production of enzymes that destroy the drug
• Most common: [blank_start]beta-lactamase[blank_end]
Hydrolyze B-lactam antibiotics by:
• Metallo-based mechanism of action
• Serine-based mechanism of action
B-lactamase inhibitors: [blank_start]clavulanic acid[blank_end], [blank_start]sulbactam[blank_end], and
[blank_start]tazobactam[blank_end]- Abeta-lactamase
- Bclavulanic acid
- Csulbactam
- Dtazobactam
37Acquired Antibiotic Resistance:
1. [blank_start]Efflux[blank_end]
2. [blank_start]Target Site Modification[blank_end]
3. [blank_start]Acquisition of New Targets[blank_end]
4. [blank_start]Enzymatic Inactivation of Antibiotics[blank_end]- AEfflux
- BTarget Site Modification
- CAcquisition of New Targets
- DEnzymatic Inactivation of Antibiotics
38Acquired Antibiotic Resistance
[blank_start]Efflux[blank_end]
• Increases the secretion of drug
• Multidrug efflux genes are broadly conserved in bacteria and are
chromosome-encoded
• Drug-specific efflux genes are generally encoded by [blank_start]plasmids[blank_end]
• ~~Confer resistance to different antimicrobials in several organisms- AEfflux
- Bplasmids
39Acquired Antibiotic Resistance:
[blank_start]Target Site Modification[blank_end]
• Can reduce the binding affinity to the antibiotic to the target
Mechanisms:
[blank_start]Chromosomal Mutation[blank_end]
• Observed with quinolone and oxazolidinone
• Caused by mutations encoding amino acid changes in
the genes encoding enzymes used for DNA or RNA synthesis
[blank_start]Enzymatic Target Site Alteration[blank_end]
• Observed in macrolide, glycopeptide, and B-lactam
• Enzymes alter antibiotic targets resulting in reduced affinity
and effectiveness- ATarget Site Modification
- BChromosomal Mutation
- CEnzymatic Target Site Alteration
40Acquired Antibiotic Resistance:
[blank_start]Acquisition of New Targets[blank_end]
• Microorganisms acquire new cellular targets with reduced affinity to
antibiotic
[blank_start]Target site substitution[blank_end]
• Acquisition of a new enzyme that is unaffected by drugs
or creates a new pathway
Observed in MRSA
• [blank_start]Staphylococcus aureus[blank_end] evaded methicillin by acquiring a mobile element
carrying a [blank_start]staphylococcal[blank_end] [blank_start]cassette[blank_end] [blank_start]chromosome[blank_end] [blank_start]mec[blank_end] (SCCmec)
mecA gene encodes [blank_start]PBP2A[blank_end] and [blank_start]PBP2A’[blank_end]
• Reduced affinity for beta-lactams
• Responsible for methicillin resistance- APBP2A
- BPBP2A’
- CAcquisition of New Targets
- DTarget site substitution
- EStaphylococcus aureus
- Fstaphylococcal
- Gcassette
- Hchromosome
- Imec
41Acquired Antibiotic Resistance:
[blank_start]Enzymatic Inactivation of Antibiotics[blank_end]
Enzymes produced by the microorganisms inactivate antibiotics directly
• Destroy antibiotic
• Modification rendering it ineffective- AEnzymatic Inactivation of Antibiotics
42Dissemination
[blank_start]Lateral gene transfer[blank_end] (LGT)
•Two processes: [blank_start]Physical movement[blank_end], [blank_start]Incorporation into genome[blank_end]
Mechanisms of transfer
• [blank_start]Plasmids[blank_end]
• [blank_start]Transposons[blank_end] (Tn)
• [blank_start]Integrons[blank_end]
• [blank_start]Insertion sequences[blank_end]
[blank_start]Plasmids[blank_end]
• Transformation or conjugation
[blank_start]Transposons[blank_end] (Tn)
• Mobile genetic elements
• Contain transposase for nonhomologous
recombination
• Insertion sequences
• ~~~Example NR1 in [blank_start]Shigella flexneri[blank_end]
[blank_start]Integrons[blank_end]
• Genetic elements that capture mobile gene
cassettes by site-specific recombination
• ~~[blank_start]Site-specific recombinase[blank_end] (intl)
• ~~[blank_start]Primary recombination site[blank_end] (attl)
• [blank_start]Insertion sequences[blank_end]
• ~~Short DNA sequences that act as simple transposable elements- APhysical movement
- BIncorporation into genome
- CLateral gene transfer
- DPlasmids
- ETransposons
- FIntegrons
- GInsertion sequences
- HPlasmids
- ITransposons
- JShigella flexneri
- KIntegrons
- LSite-specific recombinase
- MPrimary recombination site
- NInsertion sequences
Informações
- Descrição
- Microbiology Quiz sobre MICRO LAB Quiz Chapter 12, criado por Adri Torres em 05-11-2016.
- Autor
- Adri Torres
- Idioma
- English
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- 3
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