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190 Cards in this Set
- Front
- Back
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Prokaryotic cells
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-lack true membrane-delimited nucleus
-polycistronic DNA |
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Eukaryotic cells
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have a membrane-enclosed nucleus, are more complex morphologically and are usually larger
-monocistronic (one promoter drives 1 gene) |
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Three Domain System
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Bacteria
Archaea Eukarya based on a comparison of ribosomal RNA |
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Bacteria
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usually single celled, cell wall with peptidoglycan, most lack membrane-bound nucleus, extreme environments, some photosynthesize
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Archaea
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unique rRNA sequences, NO peptidoglycan in cell walls, unique membrane lipids, some with unusual metabolism, extreme environments
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Eukarya
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Protists: larger than bacteria and archaea, algae, protozoa (motile), slime molds, water molds
Fungi: yeast (unicellular), mold (multicellular) |
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Acellular Infectious Agents
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Viruses: smallest of all microbes, requires host cell, range of diseases
Viroids (plants) and Virusoids (need helper virus): composed of ssRNA Prions: infectious proteins (mad cow disease) |
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Microbial Fossils
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Swartkoppie chert, granular silica
3.5 bya |
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Earliest Molecules
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RNA
fulfilled protein and hereditary function May have been RNA surrounded by liposomes associated with the ribosome (rRNA, tRNA, mRNA) RNA- precursor to double-stranded DNA |
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Ribozymes
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RNA molecules that form peptide bonds, perform cellular work and replication
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Stromatolites
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mineralized layers of microorganisms
-photosynthesis, cyanobacteria (2.5 bya) |
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Universal Phylogenetic Tree
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Comparisons of small subunit rRNA (SSU rRNA)
derive a value of evolutionary distance -Shows relatedness but not time of divergences |
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LUCA
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Last Universal Common Ancestor
-debated -Archaea and Eukarya evolved independently of Bacteria Arch and Euk diverged from common ancestry |
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Antony van Leeuwenhoek
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1632-1723
First person to observe and describe microorganisms accurately |
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Spontaneous generation
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living organisms can develop from nonliving or decomposing matter
(existing theory...wrong) |
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Francesco Redi
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1626-1697
discredited spontaneous generation showed maggots on decaying meat came from fly eggs |
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John Needham
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mutton broth flasks, boiled, sealed
broth became cloudy and contained microorganisms |
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Lazzaro Spallanzani
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broth in flasks, sealed, boiled
-No growth of microorganisms |
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Louis Pasteur
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-created swan-necked flask
-demonstrated micros carried out fermentations -pasteurization -saved wine industry -developed vaccines for chicken cholera, anthrax, and rabies -Saved 9yr old boy from rabies |
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John Tyndall
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-dust carries microorgs
-if no dust= sterile nutrient broths -showed existence of exceptionally heat-resistant forms of bacteria |
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Ferdinand Cohn
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heat resistant bacteria could produce endospores
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Agostini Bassi
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showed that disease of silkworms was caused by fungus
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M.J. Berkeley
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the great potato blight of Ireland was caused by a water mold
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Heinrich de Bary
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showed that smut and rust fungi caused cereal crop diseases
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Joseph Lister
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microorgs were the causal agents of disease
system of surgery designed to prevent microorgs from entering wounds (nosocomial infection) "Listerine" |
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Robert Koch
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relationship betweein Bacillus anthracis and anthrax
-Koch's postulates to establish link between a microorg and a disease |
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Koch's 4 Postulates
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1. microorg must be present in every case of the disease but absent from healthy
2. the microorg must be isolated and grown in pure culture 3. the same disease must result when the isolated microorg is inoculated into a healthy host 4. the same microorg must be isolated again from the diseased host |
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Charles Chamberland
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porcelain bacterial filters used by Ivanoski and Beijerinck to study tobacco mosaic disease
-infectious agents were shown to be viruses |
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Pasteur and Roux
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incubation of cultures for long intervals between transfers caused pathogens to lose their ability to cause disease
(attenuate) |
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Edward Jenner
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used a vaccination procedure to protect individuals from small pox
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Emil von Behring and Shibasaburo Kitasato
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developed antitoxins for diphtheria and tetanus
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Elie Metchnikoff
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discovered bacteria-engulfing, phagocytic cells in the blood (macrophages)
evidence for cellular immunity |
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Sergei Winogradsky and Martinus Beijerinck
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studied soil microbes and discovered numerous metabolic processes (nitrogen fixation)
pioneered use of enrichment cultures and selective media |
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Molecular and Genomic Methods and discoveries
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second golden age of microbiology
-restriction endonucleases (Arber and Smith) -first novel recombinant molecule (Jackson, Symons, Berg) -DNA sequencing methods (Woese, Sanger) -bioinformatics and genomic sequencing and analysis |
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Bacteria and Archaea
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cocci and rods
arrangement- plane of division, determined by separation or not size varies |
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cocci (coccus)
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spheres
diplococci-pairs streptococci- chains staphylococci- grape clusters tetrads- 4 cocci in a square sarcinae- cubic 8 cocci *NO SINGULAR COCCI |
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bacilli (bacillus)
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rods
streptobacilli- chains of rods coccobacilli- very short rods |
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vibrios
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resemble rods, comma shaped
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spirilla
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rigid helices
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spirochetes
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flexible helices
"CHI" = X = FLEXI |
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mycelium
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network of long multinucleate filaments
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Archaea shape
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pleomorphic (variable), flat, Walsbyi square, branched, unique shapes
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Sizes
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smallest= Mycoplasma
avg= E.coli large= 600 x 800 micrometer Epulopiscium fishelsoni |
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Horizontal Gene Transfer (Bacteria)
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1. Transformation- picking up DNA from outside and makes it ones own
2. Transduction- virus injects DNA into host a. generalized: virus was inside and host cell took some DNA and infects another cell (transfers old DNA to new cell) b. specialized: specific place left or right genes get genes 3. Conjugation- bacterial mating, need F-plasmid |
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Bacterial Plasma Membrane
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encompass cytoplasm
selectively permeable interacts with external -receptors, transport systems, metabolic processes Hopanoid- adds stability |
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lipid bilayers with floating proteins
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amphipathic lipids
-polar ends, hydrophilic -non-polar tails, hydrophobic membrane proteins |
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membrane proteins
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peripheral- loosely connected to membrane, easily removed
integral- amphipathic, embedded within membrane, carry out important functions |
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peptidoglycan (murein)
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Bacterial cell wall
- rigid structure lies just outside the plasma membrane -basis of the Gram stain (+) stain purple, thick peptidoglycan (-) stain pink/red think peptidoglycan and outer membrane |
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Structure of peptidoglycan
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meshlike polymer of identical subunits forming long strands
-two alternating sugars (NAG) and (NAM) -alternating D and L amino acids that form crosslinks *penicillin interferes with cross-bridging *lysozyme breaks NAG--NAM bonds |
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Gram Positive (+)
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-composed of peptidoglycan
-teichoic acids (negatively charged stick to + dye): maintain envelope, protect from environment, may bind to hosts -some have layer of proteins on surface of peptidoglycan -secrete "exoenzymes", degrade large nutrients (alpha-amylase) -small or absent periplasmic space (between plasma membrane and cell wall) |
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Gram Negative (-)
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-more complex
-LPS in outer membrane (lipopolysaccharide) -thin layer of peptidoglycan -larger periplasmic space contains many enzymes -Braun's lipoproteins: connect outer membrane to peptidoglycan |
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Lipopolysacharides (LPS)
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-Also called endotoxin (causes fever when enters blood)
-Three parts: lipid A, embedded in outer core polysaccharide, extend out O side chain (can be mutated) -contributes to negative charge, stabilize outer membrane, biofilm formation (attachment) |
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Protoplasts
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gram positive with no cell wall
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Spheroplasts
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gram negative with no cell wall
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Mycoplasma
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does not produce cell wall
plasma membrane more resistant to osmotic pressure cell wall adds on to growing chain only (need small bits to start) |
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Glycocalyx
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components outside of cell wall
capsules and slime layers S layers |
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Capsules
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-Polysaccharides
hard to remove from cell Protection: resistant to phagocytosis, dessication, Griffiths experiment- rough vs. smooth strains |
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Slime Layers
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similar to capsules except diffuse, easily removed
aids in motility |
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S layers
(Bacterial) |
Protein or Glycoprotein that self-assemble
(-) S layer adheres to outer membrane LPS (+) associated with the peptidoglycan surface (cell wall) Protection: from ions, pH, osmotic, enzymes, predation maintains shape promotes adhesion, protects from host defenses spontaneous association |
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Archaeal Cell Envelopes
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-Composed of unique lipids: isoprene units (five-carbon, branched hydrocarbon side-chains)
-Ether linkages rather than ester linkages to glycerol -capsules and slime layers are rare |
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Archaeal cell walls
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-Lack peptidoglycan
-most common cell wall is S layer -may have pseudomurein between S layer and membrane |
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Protoplast
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plasma membrane and everything within
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Cytoplasm
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material bounded by the plasmid membrane
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Cytoskeleton
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functions similar as in eukaryotes
-role in cell division, protein localization, and determination of cell shape |
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Bacterial cytoskeletal proteins
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FtsZ- many bacteria and archaea, forms ring during septum formation in cell division
MreB- many rods, some archaea, positions peptidoglycan synthesis machinery (makes cell wall in right place) CreS- crescentin- rare, maintains curve shape (vibrios) |
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Intracytoplasmic Membranes
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-plasma membrane infoldings: analogous to thylakoids of chloroplasts, rxn centers for ATP formation
-anammoxosome in Planctomycetes: organelle- site of anaerobic ammonia oxidation for energy generation. |
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Inclusions
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-granules of organic or inorganic material that are stockpiled by the cell for future use
-some are enclosed by a single layered membrane: membranes vary in composition, some made of proteins some contain lipids, "microcompartments" food pantry |
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Storage Inclusions
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nutrients, metabolic end products, energy, building blocks
glycogen storage carbon storage- PHB>>TCA cycle phosphate amino acids, cyanophycin granules (Arg-Asp) |
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Sulfur Globules
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Methionine
Cystine- disulfide bridges |
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Microcompartments
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not bound by membranes, specific fxn
-carboxysomes- CO2 fixing bacteria, contain Rubisco |
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Rubisco
ribulose-1,5-bisphosphate carboxylase |
most abundant enzyme on earth
carbon fixing |
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Other Inclusions
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gas vacuoles- buoyancy
magnetosomes- orientation to earth's magnetic field- cytoskeletal protein MamK |
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Ribosomes
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-protein and RNA, sites of protein synthesis
-entire ribosome: bacterial and archaea (70S) eukaryotic (80S) -bacterial and archaeal ribosomal RNA- 16S small subunit, 23S and 5S in large subunit |
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Nucleoid
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irregular shape
location of chromosome and associated proteins usually one closed circular, double stranded DNA molecule supercoiling and nucleoid proteins (HU) (human coiling proteins= histones) |
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Plasmids
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extrachromosomal DNA- small closed circular DNA
exist and replicate independently of chromosome: episomes- may integrate into chromosome non-essential genes: advantage to host -own origin of replication -selectable marker: gene -multiple cloning sites many copies may exist in cell stably inherited in division classification is based on mode of existence, spread, and function |
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Fimbriae and Pili
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thin hair-like proteinaceous appendages
attachment to surfaces -sex pili: longer, thicker, required for conjugation (horizontal gene transfer) |
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Flagella
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threadlike locomotor appendages outward from plasma membrane and cell wall
-motility and swarming virulence factors |
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Bacterial flagella
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thin, rigid protein structures have to be specially stained to see
composed of three parts |
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monotrichous
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one flagellum
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polar flagellum
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at end of cell
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amphitrichous
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one flagellum at each end of cell
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lophotrichous
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cluster of flagella, tuft
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peritrichous
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spread over surface, hairy beast
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Three parts of flagella
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1. filament- cell surface to the tip, hollow cylinder, flagellin protein
2. hook- links filament to basal body 3. series of rings that drive flagellar motor |
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Flagellar synthesis
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many genes and products, new flagellin moved through hollow filament = Type III-like secretion system
self-assemble -grows from tip, not base -no ATP |
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Archaeal flagella
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thinner, more than one type flagellin protein, NOT hollow
hook and basal body hard to distinguish Type IV secretions- growth occurs at base not the end -Uses ATP |
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chemotaxis
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move toward chemical attractants or away from repellents
-sensory proteins constantly sampling environment changing concentrations bind chemoreceptors of chemosensing system |
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Movement
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flagellum rotates like a propeller CCW = run forward
CW= stop and tumble Mechanism: 2 part motor producing torque |
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Mechanism of Flagellar Movement
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-ROTOR: C (FliG protein) ring and MS ring turn to interact with stator
-STATOR: Mot A and Mot B proteins, form channel and produce energy through proton motive force -torque powers rotation of basal body and filament |
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Spirochete Motility
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-Flexible
-Multiple flagella form AXIAL FIBRIL which winds around cell -remain in periplasmic space -corkscrew shape= flexing and spinning movements |
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Twitching/ Gliding
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-Type IV pili and slime
-twitching: Brownian motion- pili at ends, short jerky, cells in contact with each other and surface -gliding- smooth |
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Myxococcus xanthus
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Type IV pili move in large groups
adventurous gliding slime adhesion complexes |
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Bacterial Endospore
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-comples dormant structure formed by some bacteria, hibernation until conditions are favorable
resistant to: heat, radiation, chemicals, desiccation -position within cell is characteristic of bacteria: dye with malachite green: central, terminal, sub terminal, swollen sporangium |
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Autoclave
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best way to sterilize- kills endospores
- 121 degrees C - 15 psi pressure - Steam- kills spore - Time- have to have correct time spore forming strip tests to see if spores grew or not |
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Endospore Structure
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exosporium- thing covering
spore coat- thick layers of protein cortex- beneath coat, thick peptidoglycan core- nucleoid and ribosomes (many gram + form spores) |
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Why endospore so resistant?
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Calcium + Dipicolinic acid
SASPs: small acid-soluble DNA-binding proteins dehydrated core- won't explode like popcorn spore coat and exosporium protect |
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Sporulation
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Process of endospore formation
occurs in hours (up to 10) commences when growth ceases- lack of nutrients complex multistage process *Spore is engulfed inside self and rest of cell dies |
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Germination
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endospore >> vegetative cell in favorable conditions
1. activation: prepares spore, results from treatments like heating 2. germination: nutrients present, spore swells and rupture of absorption of spore coat, *most vulnerable at this point 3. outgrowth: emergence of vegetative cell |
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Eukaryotic Microorganisms
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Two Groups:
Protists Fungi |
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Eukaryotic Cells
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-membrane-bound nuclei
-membrane bound organelles - intracytoplasmic membrane complex- transport- can generate energy -more complex and larger than bacteria or archaea |
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Eukaryotic Cell Envelope
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plasma membrane and all coverings external to it
-plasma membrane is lipid bilayer: phosphoglycerides, sphingolipids, cholesterol (all for strength) -Many lack a distinct cell wall -Algae: cell walls have cellulose, pectin, and silica -Fungi: cell walls have cellulose, chitin, or glucan |
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Cytoplasm of Eukaryotes
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-cytosol = liquid
-many organelles -cytoskeleton: network of interconnected filaments microfilaments= actin, alpha/beta tubulin, intermediate filaments (keratin) , motor proteins |
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Beta- Actin
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control for Western Blot tests, compare two different cell types, loading control for same amount of protein.
Western blot detects presence of protein using antibody electrophoresis- separates by size and charge |
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microfilaments
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tiny, 4-7 nm in diameter
scattered within cytoplasmic matrix or in networks and parallel arrays composed of ACTIN cell motion and shape changes |
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intermediate filaments
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keratin and vimentin classes
form barriers: tight junctions in heart, skin, digestive tract |
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mictrotubules
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thin cylinders, alpha/beta tubulin
maintain cell shape intracellular transport cell division |
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Colchicine
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blocks or stops cell division
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Secretory Endocytic Pathway
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move materials into the cell from outside, inside to outside, and around within cell
-ER- closest to nucleus, RER (rough, ribosomes)> proteins> outside cell, smooth= lipids -Golgi- decorating -Lysosomes- digestion |
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Endoplasmic Reticulum (ER)
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branching and fusing membranous tubules and flattened sacs- cisternae-
RER- ribosomes attached, makes secreted proteins Smooth ER- no ribosomes, makes lipids Fxns: transports proteins and lipids within cell, major site of cell membrane synthesis (phospholipid bilayer) |
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Golgi Apparatus
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Made of stacked cisternae
Dictyosomes: stacks of cisternae Trans face- toward cell membrane Cis face- toward ER -modify, package, secrete materials |
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Lysosomes
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membrane-bound vesicles
intracellular digestion Hydrolases= enzymes which hydrolyze molecules (like slightly acidic conditions) maintain acidic levels by pumping protons in |
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Details of Secretory Pathway
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-proteins destined for membrane, endosomes, lysosomes, and secretion are made by ribosomes on RER, released in small budding vesicles from RER
-Vesicles > cis face of Golgi > trans face of Golgi > gets tag for final destination -vesicles released from trans face of Golgi -some go to endosomes and lysosomes -some go to cell membrane- constitutive (always occur, housekeeping) secretory- store proteins until signal to release (neutrophils) -Quality assurance: unfolded or misfolded are sent into cytosol and targeted for destruction by UBIQUITIN polypeptides -Poroteasomes destroy targeted proteins |
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Ubiquitin polypeptides
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targets misfolded proteins for destruction by proteasomes
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Endocytosis
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-Bring materials into cell for use or to be destroyed (pathogens)
-taken up and enclosed in vesicles pinched from plasma membrane |
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Phagocytosis
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-type of endocytosis - cell eating
-use cell surface to surround and engulf particles -fuse with lysosomes and form new vesicles called Phagosomes |
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Clathrin-dependent Endocytosis
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-Clathrin coated pits on regions inside cytoplasmic side of membrane bind macromolecules to give signal
*Receptors binding *Receptor-mediated endocytosis |
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Calveolae-dependent endocytosis
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cholesterol and caveolin (membrane protein)
pinch off to form caveolin-coated vesicles don't deliver to lysosomes may play in signal transduction and transport of small and macro molecules |
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Endosomes
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organelles with hydrolytic enzymes
early > late > fuse with lysosomes Caveosomes fuse with early endosomes |
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Autophagy
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-transport of materials to be digested but does not involve endocytosis- all within the cell
-macroautophagy- digest/recycle cytoplasmic components -double membrane surrounds cell and forms autophagosome -Autophagosome fuses with lysosome> contents digested > nutrients expelled > Residual body > release contents out of cell by lysosome secretion -Residual Body: takes garbage completely out of cell *Self-digestion |
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Nucleus
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-membrane bound sphere with genetic material
-Chromatin: dense complex of DNA, histones and other proteins, condenses into chromosomes in division |
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Chromatin
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DNA, histones, protein
Histones: 5 histone proteins form nucleosomes -H1 H2A H2B H3 H4 -Euchromatin: transcribed genes, less packed - Heterochromatin: more compacted |
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Nuclear envelope
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double membrane
continuous with ER nuclear pores- allow transport in/out, gated |
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Nucleolus
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Have 1 or more
not membrane- enclosed important for ribosome synthesis: makes and processes rRNA, assembles rRNA and ribosomal proteins to form partial ribosome subunits, ribosomes mature in cytoplasm |
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Eukaryotic Ribosomes
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Larger than bacterial and archaeal ribosomes (70S)
80S in size 60S is bound to ER (RER) free ribosomes- make nonsecretory and non-membrane proteins (stay inside) |
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Endosymbiotic Hypothesis
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Mitochondria, hydrogenosomes, and chloroplasts evolved from bacterial cells that invaded or were ingested by early ancestors of eukaryotic cells
-mitochondria and chloroplasts are very similar to extant bacteria- binary fission, closed single circular DNA |
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Mitochondria
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-Powerhouse: 38 ATP from one glucose
-Tricarboxylic acid cycle (TCA cycle) -ATP generated by electron transport and oxidative phosphorylation reproduce by binary fission -outer membrane contains porins -inner membrane= cristae, location of enzymes and electron carriers -matrix- ribosomes, mitochondrial DNA, large calcium phosphate granules, enzymes of TCA cycle and enzymes involved in catabolism of fatty acids (beta oxidation) |
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Beta- oxidation
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catabolism of fatty acids
lipids store a lot of energy |
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Hydrogenosomes
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energy conservation organelles in some anaerobic protists
double membrane, no cristae, usually no DNA ATP generated by FERMENTATION PROCESS CO2 H2 and acetate or products 1 glucose = 2 ATP |
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Chloroplasts
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type of plastid: pigment containing organelles in plants/algae
photosythetic reactions double membrane chlorophyll stroma- matrix, DNA, ribosomes, lipid drops, starch granules, and thylakoids -Thylakoids: flattened membrane bound sacs |
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Stroma
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matrix of chloroplasts
site of DARK RXNS of photosythesis -forms carbs from water and carbon dioxide H2O + CO2 = carbohydrates >>> amino acids |
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Thylakoids
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Inside stroma of chloroplasts
flat sacs -Grana: stacks of thylakoids -Thylakoid membrane: site of LIGHT RXNS, trap light to make ATP, NADPH, and O2 |
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Pyrenoid
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found in algal chloroplasts
participates in polysaccharide sythesis (makes starch) |
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Cilia
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external on cell
beat with two phases work like oars |
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Flagella
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longer than cilia
undulating movement 1. tinsel- tip pulls cell along 2. whiplash- naked flagellum |
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Structure of Flagella and Cilia
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-membrane bound cylinders
-Axoneme: set of microtubles 9+2 arrangement -Basal Body: 9+0 arrangement, at the base, directs synthesis of flagella and cilia *Powered by ATP hydrolysis (in bacteria a proton pump is power source) |
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Comparison of Three Domains
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Eukaryotic cells:
-nucleus, larger, complex, meiosis, mitosis, processes (organelles) Molecular Unity to all three cell types: - biochem processes, metabolic pathways, genetic code |
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Codon preference
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redundancy of genetic code
-some codes yield the same amino acid -sequences may differ between species *How to fix? -site-directed mutogenesis: change to preferred codon, language has to match organism (E.coli vs. Human) |
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Chemotherapeutic Agents
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chemical agents used to treat disease
destroy pathogenic microbes or inhibit their growth most are antibiotics: |
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Antibiotics
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microbial products or their derivatives that kill susceptible microbes or inhibit their growth
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Paul Ehrlich
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concept of selective toxicity
identified dyes that treated African Sleeping sickness |
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Sahachiro Hato
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identified arsenic compounds that treated syphilis
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Gerhard Domagk
Jacques Therese Trefouel |
sulfonamides and sulfa drugs
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Penicillin
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first discovered by Ernest Duchesne then accidentally by Alexander Fleming
-effectiveness demonstrated by Florey, Chain, and Heatley who received nobel for discovery and production |
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Streptomycin
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antibiotic active against TB
discovered by Selman Waksman |
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General Characteristics of Antimicrobials
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-selective toxicity: kill or inhibit pathogen while damaging host as little as possible
-therapeutic dose: drug level required for clinical treatment -toxic dose: drug becomes too toxic for patient (side effects) -therapeutic index: ratio of toxic to therapeutic dose |
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side effects
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undesirable effects of drugs on host cells
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narrow-spectrum drugs
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attack only a few different pathogens
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broad-spectrum drugs
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attack many different pathogens
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cidal agent
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kills microbes
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static agent
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inhibits growth of microbes
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Effectiveness of agent
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-May vary- concentrations, microbe, host
-Effectiveness express in: 1. minimal inhibitory concentration (MIC): lowest concentration of drug that inhibits growth 2. minimal lethal concentration (MLC): lowest concentration of drug that kills pathogen |
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Determining level of antimicrobial activity (tests)
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-dilution susceptibility tests for MIC
-disk diffusion tests- Kirby Bauer -the E-test MIC and diffusion (anaerobic) |
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Dilution Susceptibility Tests
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inoculating media containing different concentrations of drug
-broth or agar with lowest concentration showing no growth is the MIC -if broth is used tubes showing no growth can be subcultured into drug-free medium (will regrow) -Broth where microbe can't recover is the MLC |
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Disk Diffusion Tests
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disks with specific drugs are placed on agar plates covered with a test microbe
drug diffuses from disk into agar, establishing concentration gradient clear zones (no growth) around disks (measure in mm from center |
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Kirby-Bauer Method
(disk diffusion) |
standardized method
sensitivity and resistance determined using tables that relate zone diameter to degree of microbial resistance table values are plotted and used to determine if concentration of drug reached in body will be effective |
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E-Test
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use with anaerobic pathogens
-similar to disk diffusion method but uses STRIP rather than disk -E-test strips contain gradient of antibiotic -intersection of elliptical zone of inhibition with strip indicates MIC |
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Penicillins
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-Inhibit cell wall synthesis
-6-aminopenicillanic acid, different side chains -Beta-lactam ring -Blocks enzyme that causes transpeptidation (NAM and NAG ropes from cross-linking while making cell wall) -*Acts only on growing bacteria that are synthesizing ne peptidoglycan -PBPs- penicillin-binding proteins -may activate autolysins in bacteria and murein (cell wall) hydrolases -stimulate bacterial holins (makes holes) 1-5% adults are allergic to penicillin |
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Beta-lactam ring
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most crucial feature of penicillins
-essential for bioactivity many penicillins are resistant to beta-lactamase (penicillinase) which is supposed to break bonds of ring |
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Cephalosporins
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-take if allergic to penicillin
-cell wall blocker -broad-spectrum -grouped into 4 categories based on spectrum |
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Vancomycin
Teicoplanin |
-Gycopeptide antibiotics
-inhibit cell wall synthesis -Vancomycin- treats antibiotic resistant staphylococcal and enerococcal infections (MRSA) drug of last resort |
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Protein Synthesis Inhibitors
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-Work at several steps of translation
-may bind specifically to bacterial ribosome (to 30S or 50S) -May inhibit any of these steps in protein synthesis: 1. A site on ribosome: aminoacyl- tRNA binding, brings right AA to anticodon 2. P-site : peptide bond formation (peptidal transferase) mRNA reading translocation (shifts to read next codon) |
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Aminoglycoside antibiotics
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PSI
large family all have cyclohexane ring and amino sugars -bind to 30S ribosomal subunit and interfere with protein synthesis by causing misreading of mRNA -Causes bad proteins to be made -drugs are bacteriocidal (kills them) |
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Tetracyclines
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PSI: 4-ring structure, variety of side chains
- broad spectrum, bacteriostatic (inhibit growth) -bind to 30S subunit of ribosome, and inhibits binding of aminoacyl-tRNA to A site of ribosome -Occupies A-site, treats acne -if stop taking drug or levels aren't maintained, bacteria will come back |
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Macrolides
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PSI: 12 to 22 carbon lactone rings linked to sugars
-Erythromycin: broad, static, binds to 23S rRNA of 50S ribosubunit *inhibits peptide chain elongation also used for people allergic to penicillin |
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Chloramphenicol
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PSI: chemically made
binds to 23s rRNA on 50S subunit *inhibits peptidyl transferase reaction -toxic with many side effects only used in life-threatening cases |
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Metabolic Antagonists
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act as false substrates
antimetabolites- antagonize or block functioning of pathways through competitive inhibition *structural analogs: similar to and compete with naturally occurring metabolic intermediates competitive= goes into active site non-competitive= changes confirmation to make fit |
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Sulfonamides or Sulfa Drugs
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MA- paraminobenzoic acid (PABA) analog
PABA- used for sythesis of folic acid, made by many pathogens *these drugs compete with PABA for the active site, so folic acid concentrations are reduced without folic acid, pathogen dies because folic acid is precursor to purines and pyrimidines (nucleic acid building blocks) |
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Trimethoprim
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MA- synthetic, also interferes with folic acid production
broad, often combined with sulfa drugs variety of side effects including abdominal pain and photosensitivity (get bad sunburn) |
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Nucleic acid synthesis inhibition
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block DNA replication: DNA polymerase, DNA helicase (winding enzyme)
block DNA transcription: RNA polymerase last resort drugs because similarities between mechanisms of humans and bacteria |
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Quinolones
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NucAcid- broad spectrum, synthetic, 4-quinolone ring
-Nalidixic acid: first to be made *inhibit bacterial DNA gyrase and topoisomerase II (relieves supercoilding ahead of fork) Bactericidal- DNA breaks, cells die |
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Antifungal drugs
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fewer effective agents because similar to eukaryotic cells (humans)
-low therapeutic index and are toxic: just a little will cause side effects -easier to treat superficial then systemic infections |
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Superficial Mycoses
(treating) |
ex. Candida (thrush)
-topical and oral -disrupts membrane permeability and inhibit sterol synthesis -disrupts mitotic spindle, may inhibit protein and DNA synthesis |
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Systemic Mycoses
(treating) |
difficult, can be fatal, three common drugs
1. Amphotericin B: binds sterols in membranes 2. 5-flucytosine- disrupts RNA fxn 3. Fluconazole- low side effects, disrupts electron transport |
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Antiviral Drugs
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slow development, hard to target viral replication
-drugs inhibit virus-specific enzymes and life cycle processes |
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Amantidine
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-antiviral
prevents influenza blocks penetration and uncoating of influenza virus |
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Adenine arabinoside
(vidarabine) |
inhibits herpes virus enzymes in DNA/RNA synthesis and fxn
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Other Antiviral Drugs
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-acyclovir- herpes DNA polymerase
-valacyclovir- prodrug of ^ -ganciclovir- antiherpes -foscarnet- antiherpes, cytomegalovirus DNA polymerase |
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HPMPC
(cidofovir) |
-broad spec anti-DNA virus drug
inhibits viral DNA polymerase, papovaviruses, adenoviruses, pox, herpes, etc. |
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Anti-HIV Drugs
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1. reverse transcriptase (RT) inhibitors
2. protease inhibitors: mimic peptide bond that is normally attacked by proteases 3. fusion inhibitors: prevent HIV entry into cells 4. cocktail of drugs |
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Tamiflu
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anti-influenza
neuraminidase inhibitor: blocks attachment |
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Antiprotozoal Drugs
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mechanism not known
- some inhibit protein synthesis 1. chloroquine and mefloquine- malaria 2. metronidazole- Entamoeba infections 3. atovaquone- pneumocystis and toxoplasma |
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Drug Resistance
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-Increasing problem
-can be transmitted to other bacteria -resistant mutants can arise spontaneously and then selected for Mechanisms: no entry, efflux (pumped out), inactivation (chemically modified), mutations in sequences, bypass pathways |
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Drug Resistant "Superbug"
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MRSA that developed resistance to vancomycin
MRSA: methicillin-resistant Staphylococcus aureus new resistant thing = VRSA also resistant to other antibiotics -came from foot ulcers on a diabetic patient -conjugation with VRE (vancomycin resistant enerococci) *Serious threat to human health |
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immunity genes
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Origin of drug resistance
-exist in nature to protect antibiotic producing microbes from their own antibiotics |
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horizontal gene transfer
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immunity genes transfer from antibiotic producers to non-producing microbes
conjugation, transformation, transduction |
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resistance genes
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found on bacterial chromosomes, plasmids (R-plasmids), transposons (jumping genes), integrons
-can freely exchange between bacteria once on mobile genetic elements |
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chromosomal genes
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resistance results from rare spontaneous mutations which usually result in a change in the drug target
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R plasmids
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resistance plasmids
can be transferred to other cells by conjugation, transduction, and transformation can carry multiple resistance genes |
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composite transposons
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contain genes for antibiotic resistance
can move rapidly between plasmids and populations |
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gene cassettes
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sets of resistance genes
can exist as separate genetic elements "super bugs" |
