Antibiotics I Flashcards
What are the primary sources of antimicrobial compounds?
Sources include natural products from fungi, bacteria (especially Streptomyces spp.), plants, insects, marine organisms, and chemical synthesis. In silico analysis and chemical libraries also provide potential antimicrobial agents.
What was the impact of Alexander Fleming’s discovery of penicillin?
In 1929, Fleming observed that Penicillium mold produced a powerful antibacterial substance, penicillin, which inhibited Gram-positive bacteria. This discovery marked the beginning of the antibiotic era, although penicillin did not affect the Penicillium species itself.
What was the significance of Eli Lilly’s Natural Product Screening Programme (1949-1959)?
The program screened 10,000 soil samples, isolated 200,000 organisms, and identified 25,000 with some antimicrobial activity. Out of these, 300 antibiotics were chemically isolated, leading to only 7 reaching the clinical stage and 3 reaching the market, demonstrating the challenges of antibiotic discovery.
Describe the structural diversity of antibiotics derived from natural sources.
Antibiotics like daptomycin, erythromycin, rifampicin, and mupirocin show significant structural diversity, targeting various bacterial functions. This diversity is essential for finding unique mechanisms of action and overcoming bacterial resistance.
What are the major classes of natural and synthetic antibiotics?
Natural products include β-lactams, aminoglycosides, macrolides, glycopeptides, and tetracyclines. Synthetic antibiotics include sulfa drugs, quinolones, streptogramins, oxazolidinones, and nitrofurans. Each class targets specific bacterial functions, mainly cell wall synthesis, protein synthesis, or DNA replication.
What are some examples of antibacterial targets?
- Cell wall inhibitors
- Cell membrane
- DNA/RNA
- Protein synthesis inhibitors acting on ribosomes
- Folic acid synthesis
How does the drug development timeline affect antibiotic discovery?
Discovery and preclinical testing can take 2-10 years, followed by clinical phases and FDA review. Only 1 out of 5,000-10,000 screened compounds typically reaches FDA approval, with development costs now exceeding $1 billion per drug, making antibiotic development resource-intensive.
Why are large pharmaceutical companies reluctant to invest in antibiotics?
Antibiotics, typically taken short-term to cure infections, generate lower revenues compared to chronic disease drugs. The rise in antimicrobial resistance, strict regulation, and public awareness of antibiotic misuse have also contributed to a decline in antibiotic prescriptions.
What factors drive the rapid emergence of antibiotic resistance?
Resistance is promoted by bacterial rapid multiplication, genetic exchange (both vertically and horizontally), a vast gene pool of resistance genes, and the selective pressure from widespread antibiotic use in hospitals, agriculture, and community settings.
Describe intrinsic resistance and give examples.
Intrinsic resistance is inherent to bacterial species, where all members are resistant to a particular antibiotic. For example, Mycoplasma lacks peptidoglycan, so it is resistant to β-lactams; E. coli is resistant to vancomycin due to its outer membrane.
How do antibiotic producers protect themselves from their own antibiotics?
Producers may lack the antibiotic’s target, modify the antibiotic (e.g., adding phosphate to aminoglycosides), modify the target to prevent binding (e.g., methylating ribosomal RNA for erythromycin resistance), or use efflux pumps to expel the antibiotic from the cell.
What are common mechanisms by which bacteria acquire resistance?
Bacteria develop resistance through genome modifications (point mutations, deletions) or by acquiring resistance genes via plasmids, conjugative transposons, bacteriophages, or environmental DNA, allowing rapid adaptation to antimicrobial agents.
Explain the role of plasmids in spreading antibiotic resistance.
Plasmids are extrachromosomal DNA that can transfer between bacterial species and genera. They carry resistance genes for various antibiotics, enabling rapid spread of multi-drug resistance within bacterial communities.
What is the role of the bacterial genetic toolkit in resistance?
Elements like transposons, gene cassettes, and integrons help bacteria capture, maintain, and transfer resistance genes, enhancing their ability to survive antibiotic treatments in diverse environments.
What is Linezolid’s mechanism of action?
Linezolid binds to the A-site of the 50S ribosomal subunit’s peptidyl transferase center (PTC), preventing aminoacyl-tRNA from binding and inhibiting protein synthesis. It was initially difficult for bacteria to develop resistance due to the multiple copies of the rRNA gene encoding the ribosome.
