Microbiology - Microbes Ch. 3 Notes

“Bacteria Reveal Their Adaptability, Threatening the Brief Reign of Antibiotics”

*Bacteria have fought back by taking advantage of their own adaptive powers to become resistant to antibiotics
*Preserving the efficacy of the antibiotics we have now but also in ensuring that future development of new antibiotics continues

*Bacteria one of the first life forms on Earth
-Live under ice in Arctic and Antarctic regions
-Boiling hot springs; nuclear wastes; underground (far)
-Important as recyclers (base of Earth’s food chain)

*Only small # of bacteria cause infections
-Most neutral/benign from human point of view
-People continue to try to eliminate bacteria from their environment
-Know your adversary: Focusing on the minority of bacteria that cause disease and striving to prevent their incursions

*Bacteria and resistance:
1. Bacteria can destroy antibiotic before hits vulnerable parts (missiles)
-Producing specific proteins - chemically modify antibiotic to a form that no longer interferes w/ the bacterial activity the antibiotic was designed to inhibit
2. Advantage of the fact that any compound that binds to a bacterial target, w/ a view to stopping its action – reach a threshold concentration in order to bind effectively
-Keep the antibiotic concentration low enough
-Revolving door strategy
~Bacterial protein pump can eject antibiotic from cytoplasm as rapidly as antibiotic moves into the cytoplasm – concentration of antibiotic in the vicinity of the ribosomes will be too low to be effective in stopping the synthesis of bacterial proteins (pumps = Efflux Pumps)
3. Chemically modify or mutate the target of the antibiotic so that the
Antibiotic no longer binds
-However: mutating or otherwise modifying such a component or process can have deadly effects on the bacterium - essential processes

*Other reasons for Antibiotic failure (other than bacteria)
-Not always due to bacterial resistance
-Misdiagnosis of infection
~If not a bacterium…Antibiotic has no effect (virus; fungus; protozoa)
~New rapid diagnostic techniques could help to make sure that antibiotics are used only when they are likely to be effective
-“The wrong pharmacokinetic properties”
~Drug does not get where it is needed
-Incomplete information
~Ignorance of what the antibiotic does
~Taking full course of antibiotics

*New generations of Antibiotics
-New versions of old favorites and new types of antibiotics
~Goal has been to modify antibiotics to counter emerging bacterial resistance strategies
-New versions: Generations of a family
~Penicillin = 1st generation; later = 2nd generation
-Continued ability of bacteria to become resistant to each new generation of antibiotic ~higher price tag
-Currently in 4th generation of most antibiotics (60 years)
~Creating yet newer generations of antibiotics
-Finding ways to prevent the development of bacterial resistance
~Prudent use of antibiotics (reduce selection pressures)
~Directly targeting and inactivating bacterial mechanisms for resisting antibiotics
EX: Augmentin: Contains a compound that inhibits the bacterial enzyme so that it can no longer destroy Amoxicillin (leaving Amoxicillin to carry out lethal task)

*Origins of Bacterial Resistant Genes
1. Gene that makes bacterium resistant to antibiotic usually resembles a bacterial housekeeping gene (responsible for essential synthetic function – building rigid cell wall/synthesis of proteins)
-Mutated into genes to protect from antibiotics targeting essential
2. Least some antibiotic resistance was present before production/use
-Other selective pressures?
-Antibiotics were first forms of germ warfare

-No one has managed to detect antibiotics in soils where microbes that produce antibiotics in the laboratory are normally found
-Basic principle of soil microbiology is that nature abhors a pure culture – areas where single species has succeeded in eliminating all competitors from immediate vicinity
-Bacteria that produce antibiotics protect themselves by also having genes that make them resistant to the antibiotics they produce – does not explain the fact that some bacteria that do not produce antibiotics have resistance genes too

*Designing strategies for controlling and slowing the increase in bacterial resistance to antibiotics on the assumption that the only selection for resistant bacteria is the use of antibiotics in modern medicine or in modern agriculture
*Selective pressures (agriculture; pollution; heavy metals) → might not be major contributors to the current rise in incidence of resistant strains
-Could be generating a constant source of small numbers of resistant bacteria, whose numbers increase dramatically if an antibiotic selection is applied

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