Micro 7: Control of microbial populations (bacterial and fungal)
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85 terms
Terms | Definitions |
|---|---|
 Aims of control | reduce #s to sanitary level, slow down/inhibit, eliminate/kill |
| Biocides | any control agent (physical or chemical) -> used to control or eliminate infectious organisms in an environment |
| Disinfectant | destroy vegetative pathogens present on surfaces, NOT used on living tissues (mechanism of action is too harsh) |
| Antisepsis | destruction of vegetative pathogens on living tissue |
| 70% alcohol | can be used both as a disinfectant and an antiseptic |
| Antibiotic | naturally occurring (microbially produced) compounds used in the treatment of disease -> also describes synthetic antimicrobials |
| Sterilization (cannot have partial sterilization) | removal of all life |
| Static effect | compound added which inhibits further growth of the microorganisms |
| Cidal effect | compound added which causes a reduction in cell numbers |
| Factors influencing choice of control and outcome | # and type of organisms (changes concentration of agent), presence of organic material, location of microbe/infection |
| Cell envelope structure (enveloped viruses and gram positive most sensitive; viruses, mycobacteria, endospores and mycobacteria most resistant) | what factor of a bacterial cell determines its response to biocides? |
| Benzalkonium Chloride (Lysol) and Triclosan | disrupts permeability of plasma membrane of bacteria and fungus, S. aureus need little concentration (gram positive - most sensitive), E. coli needs medium, P. aeruginosa needs most (varying sensitivities between groups - gram negative) |
| Physical microbial control | high temperatures (moist heat-boiling/steam, pasteurization, dry heat), ethylene oxide gas, filtration, low temperatures, radiation |
| Chemical microbial control | food preservatives, disinfectants, antiseptics, antibiotics, antifungals, antivirals |
| Disinfectant | pasteurization, boiling (coagulated proteins -> takes lots of time), steam @ atmospheric pressure, hot dry air -> use extended exposure in order to destroy endospores (heat resistant) |
| Sterilization | incineration (dry heat), steam @ 2 atm (121C), -> can kill all organisms in 15 minutes (dry heat requires 600 minutes) |
| Ethylene Oxide | alkylating agent used for sterilization-> good for heat sensitive materials (plastics, complex devices/equipment) -> utilized in a chemiclave as a gas -> transfers ethyl group into DNA -> causes mutation and causes cessation of the microorganisms -> can take up to 18 hours! |
| Phenols, alcohols and parachlorometaxylenol (only effective against fungi) | not that effective against viruses |
| Quaternary ammonium compounds (QAT -> surfactants) | only semi effective on bacteria, fungi and viruses |
| Triclosan | effective against bacteria and viruses, but limited against mycobacteria and fungi, not effective against endospores |
| Antimicrobial activity | reactions that affect 3 things -> cell components, membranes and proteins -> use hydrolysis, oxidation, alkylation, etc. |
| High risk | in close contact with a break in skin or mucous membrane introduced into sterile body areas -> use something that inactivates viruses, fungi, mycobacteria and spores -> use gluteraldehyde (cross-linking) or paracetic acid (oxidizing agents) |
| Intermediate risk | in contact with mucous membranes -> need to inactivate viruses, fungi and mycobacteria -> use alcohols (protein denaturation and coagulation) and iodophors (oxidizing agents) |
| Low risk | in contact with healthy skin or not in contact with patient -> use QAC's (surfactants) |
| Antiseptics | alcohols (60-92%), chlorohexidine (.4-4%), iodine and iodophors (.5-10%), Triclosan (.1-2%) |
| Narrow spectrum therapeutic antimicrobials | limited number of bacterial species -> metronidazole (effective only against anaerobes) -> many antimicrobials become this due to bacterial resistant |
| Broad spectrum therapeutic antimicrobials | wide range of bacterial species (aminoglycosides: gram positive, gram negative) |
| Extended | usually refers to a generation -> increased number of susceptible species compared to previous generation |
| Unique to bacteria | use as targets for antimicrobial therapy -> ex. peptidoglycans, ergosterol, specific ribosomes |
| Antibiotics that inhibit cell wall synthesis | beta-lactams, vancomycin, isoniazid, etharnbutol, cycloserine, ethionamide, bacitrocin |
| Antibiotics that inhibit protein synthesis (30S) | Aminoglycosides, tetracyclines |
| Antibiotics that inhibit protein synthesis (50S) | Chloramphenicol, Macrolides, clindamycin, linezolid, quinopristin, dolfopristin, |
| Antibiotics that inhibit nucleic acid synthesis (DNA) | quinalones, metronidazole, clofoziamine |
| Antibiotics that inhibit nucleic acid synthesis (RNA) | rifampin, rifabutin |
| Antibiotics that inhibit metabolism | sulfonamides, dopsone, trimethoprine, para-aminosalicylic acid |
| Bactoprenol | transports newly formed precursors across cell wall to be added to the cell wall (crosses by being phosphorylated/dephosphorylated |
| Bacitracin | prevents bactoprenol from being phosphorylated and can't transport monomers across the plasma membrane |
| B-lactams (penicillin and cephalosporins) | prevents cross linking of NAM and MAG molecules |
| Glycopeptides | ex. Vancomycin |
| Cephalosporins | effective against gram positive and gram negative bacteria |
| 1st generation penicillin | natural penicillin (ex. Benzyl penicillin) |
| 2nd generation penicillin | penicillinase resistant penicillins (ex. methicillin |
| 3rd generation penicillin | aminopenicillins (ampicillin) -> Acid stable |
| 4th generation penicillin | Wider spectrum of activity (also active against gram negative) -> piperacillin |
| Aminoglycosides | irreversible binding to 30S subunit -> induce codon misreading -> not effective against anaerobes (oxidative phosphorylation in anaerobes) |
| Tetracyclines | reversible binding to 30S -> block binding aminoacylated tRNA to A site |
| Macrolides | binds 50S -> inhibit transpeptidation and translocation |
| Lincosamides (clindamycin) | binds 50S -> target binding A & P sites |
| Streptogramins | binds 50S -> inhibit peptide bond formation |
| Glycopeptides | not effective against gram negative (large size = no penetration into cell) |
| Nitroimadazoles | not effective against aerobes -> requires activation by flavodoxin (absent in aerobes) |
| Penicillins and cephalosporins | not effective against mycoplasmas (no cell wall) or mycobacteria (cell wall impenetrable) |
| Synergy | positive effect of two antibiotics where their action is greater than both individually -> ex. sulfamethoxazole and trimethoprim (stops two different steps of folate synthesis to insure cell death) |
| Antagonism | effect of combination of antibiotics where their action is less than both individually |
| Indifference | effect of combination of antibiotics makes no difference than if they were added individually |
| Enterococci | have exogenous folic acid and don't have to synthesize it |
| Quantitative method to test susceptibility | broth dilution -> look for growth at different concentration -> MIC = 1st tube without visible growth, take tubes without visible colonies and plate them-> MBC = plate without visible colonies |
| Qualitiative method to test susceptibility -> Kirby-Bauer Disk diffusion method | known concentration of antibiotics -> incubate plates and look for zones of inhibition of growth -> measure diameter of the zone of inhibition and compare to standardized tables -> determine: sensitive, resistant or intermediary resistance |
| E-test strips | alternative to MIC macrodilution method -> put strip on agar plate -> look for zone of inhibition of growth -> determine effective concentration against that organism |
| Resistance | not created but microorganisms that have this are already present in population |
| Efflux pump | can remove antibiotic as quickly as it is absorbed -> creates resistance |
| Antibiotic degrading enzyme | most common type of resistance -> has enzyme that degrades the antibiotic which allows for resistance -> ex. b-lactamase |
| B-lactamase | switched on only in presence of penicillin or constitutively produced -> breaks b-lactam ring of penicillin and renders it inactive |
| B-lactamase inhibitor (clavulanic acid) | inhibits b-lactamase and allows for active b-lactam antibiotic (prevents resistance) |
| Drug inactivation | resistance mechanism that is very common in b-lactams and aminoglycosides and common in tetracyclines |
| Altered uptake | resistance mechanism that is common in b-lactams and aminoglycosides and rare in tetracyclines |
| Altered target | resistance mechanism common in b-lactams and glycopeptides and rare in aminoglycosides |
| Mechanisms of transfer (of resistance genes would be virulence factors) | plasmids = conjugation, loose DNA = transformation, bacteriophage = transduction, jumping genes = transposition; |
| Consequences of new information | degradation, stably maintained or incorporation into chromosome |
| Recombination | breaking and rejoining of DNA in new combinations |
| Homologous recombination | conjugation, transformation and transduction |
| Non-homologous (site specific) recombination | cut and paste mechanism (transposition) |
| Conjugation | only in gram negatives -> can produce F pilus -> F+ binds to F- cell and transfers half of plasmid and recipient cell (F-) can synthesize complementary strand and becomes F+ cell and can transfer to another F- cell (if transfer is interrupted it remains F-) |
| Hfr cell (high frequency recombination) | transfer of F plasmid is complete and integrated into chromosome |
| Transformation | cell lyses and releases DNA -> binds to DNA binding protein (on competent cell -> Haemophilus, streptococci -> in late log phase of growth) -> 1 strand of DNA is degraded, 2nd strand undergoes recombination and incorporation |
| Transduction | only happens by bacteriophage -> virulent (lytic form -> generalized transduction): death of cell by lysis, releasing new phage OR temperate: can switch between virulent/lytic phase & prophage (non-lytic) depending on environmental condition -> lysogeny (when bacteria are carrying a prophage) |
| Defective phage | has bacterial DNA instead of phage -> can inject resistance genes into another bacterial cell |
| Specialized transduction | can remain as non-lytic phage -> maintains stable relationship until environment switches it into lytic mode and then release defective phages |
| Transposition | jumping genes can move around within the cell -> chromosome into plasmid, chromosome to chromosome -> carry transposase (site specific recombinases) -> transposons may then be transferred via mechanisms discussed -> has insertion sequences around resistance genes |
| Antifungals | polyenes, nucleic acid synthesis inhibitors, ergosterol biosynthesis inhibitors, echinocandins (make sure they are not toxic to host - both are eukaryotic) |
| Polyenes (ex. amphotericin B) | binds to ergosterol which causes ions to be removed from cell causing cell lysis -> broad spectrum fungicide |
| Nucleic acid synthesis inhibitors (E.g., Flucytosine aka 5-fluorocytosine) | Used in conjunction with Amphotericin B to treat cryptococcosis or candidiasis; Mode of Action: Converted to 5-fluorouracil (by fungal cytosine deaminase ONLY in fungi), interferes with activity of thymidylate synthetase and synthesis of DNA, RNA and proteins (incorporates into RNA). |
| Ergosterol biosynthesis inhibitors | antifungals -> ex. Azoles (fluconazole): binds to 14 alpha-demethylase and prevents formation of ergosterols; Allylamines (terbinafine - lamisil): inhibits squalene epoxidase and causes no lanosterol or ergosterol to be formed -> both increase membrane permeability which eventually causes cell lysis |
| Beta-glucan synthesis inhibitors (Echinocandins) | ex. caspofungin, block 1, 3 b-D-glucan synthetase; Nikkomycin Z prevents synthesis of chitin (competes with UDP-NAG for chitin synthase) -> unique part of fungal cell wall (different than humans) |
| Factors contributing to antifungal resistance | mutations in cytosine deaminase, decreased rate of transport into fungal cell, alteration of target enzyme, alteration of ergosterol biosynthetic pathway, growth as biofilm |
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