12. Control of bacterial growth-antibiotics Flashcards
Why would we control bacteria growth
-To block transmission of infections and diseases
-Block of the contamination by unwanted microbes and their proliferation
-Avoid the deterioration and alteration of substances and raw materials
How can microbes be removed
By physical or chemical agents
What are principles of microbial control related to
Microbial nutrition, growth, development and structure
What is sterilization
Process that leads to destruction of all forms of microbes( living, spores and acellular entities)
What’s disinfection
Process that leads to the killing, inhibition or removal of microbial forms (not necessarily including endospores) that may cause the disease
What are some different types of agents
-Sanitizing agent: reduces microbial population to safety levels
-Bactericidal agent: kills bacteria
-Fungicidal, virucidal, sporicidal: kills fungi, viruses and endospores
-Bacteriostatic agent: inhibits bacteria growth
-Antiseptic agent: can be used on living tissues(skin) to remove or inhibit microbes(no sporicidal agents)
-Antimicrobial agent: interferes with microbial growth and activity
-Therapeutic agents: when antimicrobial agents are used for the treatment of infection
How can we control microbial growth by heat
-moist heat
-fractioned or intermitted head(tyndallization)
-Dry heat
-Pastorization-No sterilization
-Boiling, disinfection-no sterilization
What are some physical methods(other than heat) that can control microbial growth
1.Radiations
2.Filtration
3.Low temperatures: slow down and can stop metabolism. Not safe sterilization method
4. Dehydration: can stop metabolic activity. Also not safe sterilization method
What kind of sterilization by filtration do we have
-Used for liquids: membrane acts as barrier and doesn’t work on viruses and mycoplasma
-HEPA(High-Efficiency particulate air): remove viruses and particles smaller than 0.1 microM; used for air and gasses
What are fundamental requirement for disinfectant
- Be endowed with microbicidal action and preferentially sporicidal
- Do not damage the material with which in comes in contact
- Not expensive
- Not toxic or harmful for humans
- Its bactericidal action must not be neutralized or reduced by the substrates on which it acts( ex: organic matter)
What are some examples of chemical disinfectants/ sterilants
-Alcohols
-Aldehydes
-Halogens and oxidants
-Phenolics
-Detergents
-Ethylene oxyde gas
-Vaporized hydrogen peroxide
What’s the pyramid of mo that are least susceptible/ most resistant to chemical biocides
HIGH: prions, endospores (need oxidizing and alkylating agents).
INTERMIDIATE: oocysts, mycobacteria, non-enveloped viruses, protozoal cysts, filamentous fungi, vegetative Gram negatives
(vegetative bacteria refers to those that can actively divide and cause an infection as opposed to bacterial endospores (which are dormant and form as means of survival)
LOW: yeasts, protozoa, vegetative Gram positive, enveloped viruses
Enveloped viruses are partially susceptible to membrane active agents including both biocides and detergents
What do mechanisms of action of biocides depend on
Main bacterial structure targeted
What are some reversible and irreversible actions that biocides can do to the bacterial cell
REVERSIBLE: initial release of intracellular potassium which causes loss of proton motive force(PMF) and membrane potential necessary for synthesis of ATP. Active transport stops, as well as normal metabolic processes and replication
IRREVERSIBLE: under continued exposure, it can come to: change in cytosolic pH, disruption of enzymatic function and coagulation of intracellular material, loss of cytoplasmic constituents( proteins, nucleoids, pentoses, ions)
What disrupts outer membrane of Gram - bacteria that isn’t considered a biocide
EDTA
What kind of biological agents do we have for microbial control methods
Predator (antisepsis), viruses(antisepsis) and toxins(sterilization)
What are the factors affecting the antimicrobial action of a disinfectant
-population composition
-physiological state of the cell
-population size
-concentration of biocide
-contact time
-local environment, presence of organic matter
-chemical formulation of disinfectant, temperature, pH
Why are there complications when biofilm is formed
Organic matter in biofilm protects the biofilm’s residents
What are some intrinsic factors governing microbial resistance and tolerance in biocides
a)vegetative bacteria: impermeable barrier, cell surface properties(fatty acid composition, charge), pigments( melanins, carotenoids), export by effux pumps
b)endospores: DNA protection mechanisms
c)sessile biofilm: nucleic acid protection( SOS response), diffusion barrier, cell-cell communication
What are antimicrobial agents
Antibiotics and chemotherapeutics
What are antibiotics
Chemical agents synthesized by microorganisms able to inhibit or kill other microorganisms
What are chemotherapeutics
Synthetic chemical agents able to either inhibit or kill other mo
Who produces antibiotics
Soil bacteria( Bacillus) or fungi( Penicillium)
Are producers of antibiotics resistant to the antibiotic they synthesize
Yes, that’s the origin of resistance genes
Why are species producing antibiotics
To compete with other mo for the colonization of new environmental niches
What kind of compounds are antibiotics
They have low molecular weight and inhibit microbial growth at low concentrations. Their chemical structure is very complex and they can belong to different chemical classes. They are secondary metabolism products
Are secondary metabolites essential for survival
No
What are primary metabolites
Primary metabolites- products of cellular metabolism that are produced during active growth such as: aminoacids, nucleotides, coenzymes… They are essential for growth and common in all mo
What are secondary metabolites
Secondary metabolites: produced by some microbial straints and are not essential for the growth of that strain. Usually are produced when cell growth is completed and can derive from product of microbial metabolism obtained after a series of intermediate metabolites. Hyperproduction can be induced
Who produces secondary metabolites
Filamentous fungi, filamentous Actinomycetales
Can some strains be better than the other when producing antibiotics
Yes
Why is it only that we focus on few species when producing antibiotics
Less than 1% of microbes are antibiotic producers and some of them are unculturable or very difficult to isolate
What’s Actinomyces spp
Gram + bacteria. Ramified structure gives them the aspect of fungus but they are structurally different bc they don’t have a septum. These are the main secondary metabolites producers among bacteria
What bacteria produces the most of the clinically used antibiotics
Streptomyces spp
How to mo avoid toxicity from their own antibiotics
Antibiotics are selective. They attack parts that aren’t present in the host organism (cell wall) and avoid similar targets(ex: if host and other organism have the same ribosomes)
What are bacteriostatic, bactericidal and bacteriolytic agent
Bacteriostatic: inhibits bacteria growth but doesn’t kill mo
Bactericidal: kills bacteria
Bacteriolytic: kill and lyse bacteria. Bacterial lysis may favour release of toxinsq
What do effects of bacterial agents depend on
Concentration and type of mo
what’s antimicrobial septum
Activity range of the antimicrobial agent
What kind of antimicrobial spectrum do we have
-Broad spectrum: can inhibit most of Gram + and Gram - bacteria
-Narrow spectrum: active only against limited variety of mo
What’s MIC
Minimal inhibitory concentration, the lowest concentration of a drug that prevents the growth of a particular mo. Can be determined either in a liquid or solid medium
What is the name of antibiotic sensitivity test
Kirby-Bauer test, MIC is the function of the diameter of the halo of inhibition
What are targets of mechanism of action of antibiotics
-Peptidoglycan synthesis
-Protein synthesis: translation, ribosome binding, RNA translocation
-Transcription
-DNA synthesis
-Membrane integrity
-Metabolism
What are one of the mechanism of action in antibiotics
-inhibition of the cell wall synthesis
*inhibition of transpeptidase: by stereochemical analogy. Transpeptidase forms complex penicilloy-enzyme(irreversible and lethal. Penicillin has chemical structure similar to the D-Ala-D-Ala chemical backbone that is recognized by transpeptidase
What happens when penicillin inhibits cell wall synthesis
Osmotic pressure rises, cell swell and lyses
What’s vancomycin
Interacts with terminal D-Ala-D-Ala dimer in the pentameric lateral chains and interferes with formation of peptidic bridges
Active only in Gram + because it’s a large molecule that can’t cross outer membrane (intrinsic resistance by the cell)
What does bacitracin do
Inhibits dephosphorylation of the lipid transporter of peptidoglycan precursors +(bactoprenol)
How can protein synthesis be inhibited
By binding to the 30S or 50S subunit of the ribosome. Binding to the elongation factor G
How can synthesis of nucleic acids be inhibited
By inhibiting DNA or RNA synthesis or by using metronidazole
What are some mechanisms of protein resistance
-absence of the target
-mutation of the target
-no drug permeability
-modification of the target
-inactivation of the target
-synthesis of alternative target resistant to the drug
-transport of the drug outside of the cell
Where are mechanisms of antibiotic resistance encoded
In the genes located into chromosome, mobile elements and plasmids
How can some cell have multidrug resistance
- Decrease in the outer cell permeability
-Efflux mechanisms: due to overexpression or induction of multidrug efflux transporters. These transporters grant resistance to different structurally unrelated antibiotics and other xenobiotics