Lecture 20- Antimicrobial Drugs; Antibiotics Flashcards
(19 cards)
Infectious agents
Microorganism that can cause an infection or infectious disease
Bacteria; prokaryotes- intracellular and extracellular
Fungi; eukaryotes- intracellular and extracellular
Protozoa; eukaryotes- intracellular and extracellular, parasitic or free living
Complex- internal structures- mouth e.g. plasmodium causes malaria
Virus- sub-cellular; intracellular only, uses host cells to replicate
Prions- sub-cellular- intracellular only, abnormal protein causes other proteins to fold incorrectly
The bacterial cell
Prokaryotes= lack a nucleus and other membrane bound organelles
Supercoiled DNA into a circular pattern
2 distinct categories based on cell envelope;
Gram positive and gram negative
Shape;
Bacillus= rod shaped
Coccus= spherical shape
Spirochete = spiral shaped
Filamentous= long chains of cells
Bacterial cell envelope
Gram negative; contains an LPS- endotoxin
Antimicrobial protection (LPS has a - charge) but some bacteria can modulate this to repel + charged antimicrobials
Why do we need antimicrobial drugs?
- reduced morbidity
- lower mortality rates
- increased survival rates with co-morbidities
- increases surgical survival risks
- more productive
- reduces risks at birth
- reduces economical issues
- fewer healthcare administrations
Bacterium- harming host
Main goal of bacteria cell= multiply - killing host would kill bacteria = no nutrients
Successful bacteria= obtain nutrients and spread with the least amount of energy and host damage
Causing host damage;
- to facilitate invasion
- access and liberate nutrients
- reduce competition from other microbes
- disseminate in environment
- accidental?
Bacterial pathogenesis
Exposure > adherence > invasion > infection > toxicity > invasiveness > tissue damage, disease
Bacterial infections- key definitions
Pathogen= microorganism that can cause a disease
Obligate/ primary pathogens= can breach defences and cause disease in a healthy host; all viruses are obligate pathogens, mycobacterium tuberculosis
Opportunistic pathogens; cause disease in a compromised host; weakened immune system
Intracellular pathogens; grow and replicate inside host cells; M.tuberculosis, salmonella and chlamydia trachomatis
Some roles of the microbiome
Digestion; help break down complex carbohydrates and fiber
Metabolism; folate (vit B9) -> important in RBC formation -> humans cannot synthesis vit B9 -> bacteria can;
- support the immune system;
- direct competition; attachment sites and nutrient availability
- antimicrobial production; change the pH, more acidic, antimicrobial peptide (+ charged) production
Key definitions
Minimum inhibitory concentration;
Minimum concentration of the antibiotic required to inhibit the growth of the test organism
Minimum bactericidal concentration;
Minimum concentration of antibiotic required to kill the test organism
Bacteriostatic
Bactericidal
Time dependent killing= time it takes for a pathogen to be killed by antimicrobial exposure
Bacteriolytic - lysozyme
Good example to show bacteriolysis
Lysozyme can hydrolysis the cross links (B1-4 glycosidic links) = holds peptidoglycan together
Lysozyme is in an antimicrobial enzyme present in many body fluids; tears, saliva and sweat
Crosslink breakage leads to = peptidoglycan degradation and cell lysis/ death
Good antimicrobial
Drug specificity, stability, action, toxicity, cost and resistance risk
Antibiotic- spectrum of activity
Not all antibiotics kill all bacteria
Gram negative bacteria= resistant to penicillin
Broad spectrum antibiotics= active against both gram positive and gram negative
Narrow spectrum antibiotics= only kill a certain group of bacteria; useful if infecting agent is known/ other therapies fail
E.g. vancomycin = treatment of penicillin resistant gram positives
Sulphanilamide = not affect the patient
Humans cannot synthesise folic acid
Folic acid = through diet
Do not use chemical pathway
Still has adverse effects due to hypersensitivity
Synthetic antimicrobial- sulpha drugs
Without nucleotide biosynthesis= bacterial cell will die
Resistance mechanisms = stop drug from working
Bacterial producers of antibiotics
Most antibiotics = produced by bacteria
Important bacterial producers of antibiotics =
Streptomyces species; filamentous soil bacteria = produce geosmin
B-Lactams- mode of action
Penicillin beta-lactam ring mimics D-Ala-D-Ala peptide bond
Penicillin will bind and irreversibly block the active site of PBP- enzyme cannot tell the difference
Side chain linking = blocked - cells will ultimately lyse (bacterial cell (autolysin)) keeps cutting holes but PBPs can’t fill the holes -> peptidoglycan loses structural integrity
Beta-lactates = only kill actively growing cells
Greater effect on gram + cells
Glycopeptides- another peptidoglycan target
Important member= vancomycin
Inhibitors of cell wall biosynthesis ; like beta-lactams
^ binds to D-Ala-D-Ala
- blocks transglycosylation and transpeptidation (PBP- penicillin binding protein- cannot get to substrate)
- no cross linking of peptidoglycan subunits -> cell lysis
Narrow spectrum;
Only active against some gram + bacteria; inc some staphylococcus aureus
Toxic to human; strong side effects
Inhibiting protein synthesis; aminoglycosides
Broad spectrum activity; not anaerobes = pass through cell membranes using O2
Target the 30S subunit of bacterial ribosomes by binding to the 16S rRNA
Aminoglycosides binding -> structural change of 30S subunit
Amino acid proof reading errors
*truncated (short + faulty) and aberrant (correct length- wrong AA) proteins -> usually bactericidal
E.g. kanamycin
- can inhibit gram + and gram -
- mostly used if other drugs fail
- used in molecular biology applications = used in resistance cassettes - plasmid uptake
Bacterial antibiotics - tetracyclines
Inhibits protein synthesis by interfering with the 30S subunit and binding to 16S rRNA
Inhibits binding of aminoacyl-tRNAs to the A-site
Usually considered bacteriostatic
Characterised by a napthacene ring system (tetra and cycline= 4 rings)
Natural and semi-synthetic derivatives due to modifications to the side groups of the naphthacene ring
Important in medicine, veterinary medicine and as growth promoters for live stock
