what are the requirements for useful antibiotics
- can be natural, semi synthetic, or synthetic
- chemically stable (can be produced and stored for later)
- water soluble (soluble in host tissue)
- non allergenic/low side effects
- inexpensive
- selective toxicity
what is chemotherapy
- use of chemical substances to treat diseases
what is antimicrobial agent
- any substance that kills or inhibits microorganisms
what is antibiotic
- a natural antimicrobial substance produced by microorganisms
what is semi-synthetic and synthetic
- Semi-synthetic: Chemically modified natural antibiotic (e.g., amoxicillin).
- Synthetic: Fully man-made antimicrobial (e.g., sulfonamides).
what is therapeutic index
- Ratio of toxic dose to therapeutic dose — high index = safer drug
explain selectivity and spectrum
- selective toxicity and high therapeutic index (toxic dose : therapeutic dose)
- selectivity is often influenced by mechanism of action
- also influences spectrum of effectiveness against pathogens
explain the structure, source, mode of action, resistance, spectrum, and side effects for penicillins
structure - beta lactam ring is central, differ in side chains
source - natural (penicillium) and semi-synthetic (amoxicillin)
-> V and G are natural
mode of action - interferes with cell wall synthesis (blocks peptidoglycan cross linking)
resistance - beta-lactamases -> chops beta lactam ring so it can no longer bind to ring it targets
spectrum - mainly gram positive, low against gram negative (penicillin)
-> ampicillin active against gram + and -
side effects - allergic reactions (diarrhea, anemia, hives)
explain the structure, source, mode of action, spectrum, and side effects for aminoglycosides
structure - contains cyclohexane ring and amino sugars linked by glycosidic bonds
source - streptomycin = naturally, some semi-synthetic
mode of action - disrupt peptide elongation during translation as they bind to ribosomal RNA of 30S subunit causes early termination due to mRNA misreading
spectrum - treat infections caused by gram negative (aerobic gram negative bacteria)
side effects - due to ability to bind host mitochondrial ribosome, share the same binding site as their bacterial ancestor
-> can cause nephrotoxicity (kidney damage) and ototoxicity (hearing loss)
- streptomycin and gentamicin
explain the structure, source, mode of action, spectrum, and side effects for tetracyclines
structure - 4 cyclic ring structure with side chains
source - naturally by streptomyces (chlortetracycline, doxycycline)
mode of action - similar to aminoglycosides, bind to 30S subunit blocking tRNA attachment, inhibiting protein synthesis
spectrum - active against gram + and -, and intracellular bacteria (chlamydia)
-> bacteriostatic = stops growth rather than killing
side effects - tooth discoloration, liver damage, GI upset
explain the structure, source, mode of action, spectrum, and side effects for macrolides
structure - ring structure of 12-22 carbons called lactone ring, linked to 1 or more sugars
source - streptomyces, can ne natural, synthetic or semi synthetic
mode of action - binds 50S ribosomal subunit blocking peptide exit and inhibits bacterial protein elongation
spectrum - effective against gram + and -
-> bacteriostatic = inhibits growth but doesn’t kill
side effects - nausea, diarrhea, liver damage
-> erythromycin
aminoglycosides, tetracyclines, and macrolide antibiotics affect the same major process in microbial cells - what is it
- protein synthesis
why are aminoglycosides considered bacteriocidal while tetracyclines and macrolides are only bacteriostatic
- aminoglycosides impact protein sequence, kills them
- tetracyclines and macrolides interfere with translation but not with the sequence, stops their growth
how does bacteriostatic vs bacteriocidal affect their use and effectiveness as antibiotics
- Bacteriostatic drugs are effective when patient has a functioning immune system to eliminate the inhibited bacteria.
-> infection is less acute or chronic (e.g., acne, urinary tract infections).
Examples: Tetracyclines, Macrolides, Sulfonamides. - Bactericidal drugs are preferred infection is severe or life-threatening (e.g., meningitis, endocarditis, septicemia).
-> immune system is weak (immunocompromised patients), Rapid bacterial killing is needed to prevent toxin release or spread.
Examples: Penicillins, Aminoglycosides. - Bacteriostatic antibiotics may require longer treatment durations, since they rely on immune clearance.
- Bactericidal antibiotics usually lead to faster symptom relief, but can sometimes cause endotoxin release in Gram-negative infections when cells lyse.
explain the structure, source, mode of action, spectrum, and side effects for sulfa drugs and trimethoprim
sulfa drugs :
structure - analogous of PABA (para-aminobenzoic acid)
source - synthetic
mode of action- interferes with folate synthesis, blocks the enzyme using PABA
spectrum- effective on gram + and -
side effects - allergies, nausea, skin rashes
-> sulfamethoxazole
trimethoprim:
structure - mimics dihydrofolic acid, pyrimidine derivative
source - synthetic
mode of action - interferes with folate synthesis, inhibits bacterial DHFR, blocks DNA synthesis
- binds to dihydrofolate reductase = responsible for converting dihydrofolic acid to tetrahydrofolic acid
spectrum - mainly gram negative, used to treat UTI
side effects - GI upset
- synergistic when used together, blocks 2 steps in same pathway
what are the 4 mechanisms of antibiotic resistance, describe them
- altered antibiotic target -> prevent access to or alter the target of the antibiotic so its no longer effective (MRSA replaces its transpeptidase so no binding site for beta-lactam antibiotics)
- degrade the antibiotic -> using antibiotic degrading enzyme (hydrolysis of beta lactam ring of penicillins) (aminoglycosides = acetylation of amino groups and phosphorylation of adenylation of hydroxyl present)
- alter the antibiotic to prevent them from being effective
- rapidly extrude the antibiotic -> efflux pump to move antibiotic out of the cell so it can no longer access the part of the cell its trying to target - protons move in as drug moves out
how does antibiotic resistance arise
- due to mutation and can be spread through horizontal gene transfer
- ## misuse and overuse of antibiotics drive the emergence and spread of antimicrobial resistance
why is antimicrobial resistance a concern
- Standard treatments become less effective or fail.
- Infections last longer and are more severe.
- Higher risk of death from resistant infections.
- Spread of resistant microbes increases public health risks.
- Medical procedures (surgery, chemotherapy) become riskier.
- treatment costs rise (longer hospital stays, stronger/more expensive drugs).
how can we control/prevent AMR
- monitor the use of antibiotics
- monitor the prevalence of AMR in different organisms
- improve AMR detection and monitor
- research to understand where and when AMR transfer occurs
- prevent infection from occurring
- equitable access to antibiotics globally
- development of new antibiotics
what are resistance genes
- evolved in response to the existence of antimicrobial agents
- many of these are ancient and occur in nature
- the presence of antimicrobial agents in the environment increases selection pressures that increase the prevalence of antimicrobial resistance
-> resistant populations survive and proliferate - resistance genes are often present on plasmids
-> can be transferred between microbes by horizontal gene transfer
