microbio lecture 11 notes
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Lecture 11 – Chemotherapy and Antibiotics
Introduction- antimicrobial drug: chemical substance that destroys disease-causing microorganisms w/ minimal
damage to host tissues- chemotherapeutic agents: chemicals that combat disease in the body- natural antibiotic: chemical produced by a microorganism that inhibits or kills other microorganisms
at low conc. -> most are not useful b/c of poor uptake or toxicity- semi-synthetic antibiotic: chemically modified natural antibiotics- synthetic antibiotic: wholly synthesized in the lab Natural and semisynthetic penicillin- natural: produced by the mold Penicillium, effective against gram + cocci and spirochetes- semisynthetic: made in the lab by adding different R groups onto B-lactam ring made by fungus
o resistant to penicillinases and have broader spectrum of activity than naturalSpectrum of antimicrobial acitivity- fungal infections are more difficult to treat b/c they have eukaryotic cells- narrow-spectrum: affect only select grp of microbes (ex. gram +)
o ex. small hydrophilic drugs affect gram -- broad-spectrum: affect large number (ex. both gram + and -)Effect of combinations of drugs- synergistic: more effective when taken together (1+1 =3)- antagonistic: when taken together, both become less effective when taken aloneMechanisms of action of antimicrobial drugs (either bactericidal – kill v. bacteriostatic – inhibit growth)Antibiotics: effective against bacteria, NOT against viruses1. inhibition of cell wall synthesis: inhibit peptidoglycan synthesis
- ex. beta-lactams (penicillin), vancomycin, bacitracin2. inhibition of protein synthesis: inhibit translation
- ex. chloramphenicol, macrolides, tetracyclines -> act on prokaryotic ribosomes3. inhibition of nucleic acid synthesis: inhibit DNA replication, mRNA transcription (inhibit DNA gyrase)
- ex. quinolones, rifampin4. damage to plasma membranes: alter cell membrane rigidity (ex. polymyxin B)5. act as antimetabolites: inhibit enzyme activity or synthetic metabolic inhibitors
- ex. sulfonamides or growth factor analogsAntivirals: target virus-specific enzymes and processes- ex. nucleoside analogs and other drugs that inhibit nucleic acid polymerases and viral genome
replicationo host cells produce interferon proteins that stop viral replicationo nucleoside/nucleotide analogs inhibit DNA or RNA synthesiso amantadine blocks penetration or uncoating of influenza A viruso agents like protease inhibitors (PIs) interfere w/ HIV maturation steps
Antifungal drugs: b/c fungi are Eukarya, selective toxicity is hard to achieveAntiprotozoan drugs: treat parasitic protozoan infections -> stop DNA synthesis by intercalation b/w base pairsAntihelminthic drugs: treat parasitic worms (Helminths)
Effectiveness of Chemotherapeutic AgentsTests to guide chemotherapy- used for 1) to determine which agent is most likely to combat a specific pathogen, 2) when
susceptibility cannot be predicted, 3) when drug resistance arises
Lecture 11 – Chemotherapy and Antibiotics
- Disk-diffusion method: in Kirby-Bauer test, filter paper disks impregnated w/ antibiotic are overlaid on bacterial culture inoculated on agar medium
o Absence of microbial growth = zone of inhibitiono Diameter, when compared w/ standardized reference table, determines if organism is
sensitive, intermediate, or resistant to drug- Broth dilution tests: microorganism is grown in liquid media containing diff. conc. of agent
o Minimum inhibitory conc. (MIC): lowest conc. capable of preventing microbial growtho Minimum bactericidal conc. (MBC): lowest conc. that kills bacterial
Antimicrobial Drug Resistance- 6 mechanisms of drug resistance
o prevention of penetration to target site = lack of entryo rapid efflux (actively pumping the drug out of the cell) (greater exit)o enzymatic inactivation of the drugo alteration of drug target (drug can’t bind target)o development of resistant alternative metabolic pathway
- development of antimicrobial drug resistanceo resistance is accelerated by indiscriminate use of antimicrobial drugs (overuse or misuse)o results from selection of resistance genes, R-factors, that are chromosomal or carried by
plasmids and transposonso some are multiple drug resistant (MDR)o superinfections: when a pathogen develops resistance to the drug being used or when
normally resistant microbiota multiply excessivelySearch for new antimicrobial drugs- analogs of existing drugs are often developed to be used as next-gen- computer drug design- chemicals produced by plants and animals provide new agents, including peptides- new antimicrobials include DNA that is complementary to specific genes in a pathogen -> the DNA
will bind to pathogen’s DNA and inhibit protein synthesis