Antimicrobial Agents and Resistance

antimicrobial breakpoint

→ the agreed concentration of an agent at which bacteria can, and cannot, be treated with the antimicrobial agent in question.

→ This will be related to the dose needed to treat susceptible bacteria

→ essentially, the breakpoint is a man-made or rather decided concentration, which corresponds to a dose required to inhibit bacterial growth in relevant infections

pharmacokinetics

the branch of pharmacology concerned with the movement of drugs within the body

antimicrobial resistance

the ability of a pathogenic bacteria to develop a resistance to the effects of an antimicrobial medication

bactericidal

the killing of bacteria

bacteriostatic

to inhibit or stop bacterial growth, NOT kill bacteria

antibiotic

an antimicrobial substance active against bacteria, usually produced by microbes

(fungi and other bacteria including Bacillus and Streptomyces)

*natural*

disinfectant

→ a chemical agent that kills microbes

→ they vary in their range of effectiveness killing certain microbes or microbial cell types (ex. spores)

→ these agents are generally too toxic for internal use but useful as an antiseptic or cleaning surfaces

→ ex: chlorine, alcohols, detergents

antimicrobial agents

→ an antimicrobial substance active against bacteria

→ includes natural products (ex: antibiotics) or man-made compounds

bioavailability

the portion of the drug that reaches its site of action

do antibiotics affect animal viruses?

false/no

competition strategies

out complete, kill competitor or specialize

antibiotics target …

features or enzymes unique to or susceptible to bacteria

resistance

→ with time, microbes eventually develop resistance to antimicrobial agents

→ generally adds to resistance, accounting for multi-drug resistance exhibited by many important clinical pathogens

→ resistance exhibited by a specific pathogen can vary depending on animal host. This may reflect differences in selection pressure or other ecological factors unrelated to antimicrobial usage

→ country borders are no deterrent to the spread of antimicrobial resistance

→ antimicrobial resistance is one of several public health concerns facing us today

mechanisms of antibiotic resistance

→ alter or destroy antibiotic

→ modify target

→ exclude antibiotic from cell

intrinsic resistance

→ “they’re born with it”

→ natural property of bacterial group

spontaneous mutation to resistance

→ “become resistant through natural selection”

→ spontaneous mutation in target gene, usually, and natural selection of variant gene with reduced binding to antibiotic

→ antibiotic use selects for mutants

Acquired Resistance

→ “picks up foreign gene”

→ resistance is acquired through the genetic exchange, picking up resistance gene that resid on plasmid or transposon

conditional resistance

“under certain circumstance they are resistant”

silent resistance

“turning on resident resistance gene”

natural transformation

→ uptake of naked DNA

→ few bacteria species, naked DNA is vulnerable to nucleases

generalized transduction

→ phages

→ DNA transferred via phages (“mistaken packaging of resistance gene or plasmid")

→ low-frequency event, narrow to broad host range (receptors)

→ restriction enzymes, lysogeny/phage conversion

conjugation

→ cell to cell transfer of DNA

→ requires cell to cell contact

plasmid

is an extrachromosomal DNA molecule within a cell that is physically separated from chromosomal DNA and can replicate independently of the chromosome. They are most commonly found as circular, double-stranded DNA molecules in bacteria

transposons

→ “jumping genes”

transposons and integrons are responsible for …

building “multi-drug” resistances on plasmids