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MC310 Exam 2 Review
| Question | Answer |
|---|---|
| function of plasma membrane | selectively permeable barrier, nutrient and waste transport, location of many metabolic process, detection of environmental cues for chemotaxis |
| Gas vacuoles | inclusion that provides buoyancy for floating in aquatic environments |
| ribosomes function | protein synthesis |
| functions of inclusions | storage of carbon, phosphate, and other substances |
| Nucleoid function | localization of genetic material |
| Function of periplasmic space for gram neg bacteria | contains hydrolytic enzymes and binding proteins for nutrient processing and uptake |
| periplasmic space in gram pos bacteria | may be smaller or absent |
| Function of cell wall | protection from osmotic stress, helps maintain cell shape |
| function of capsules and slime layers | resistance to phagocytosis, adherence to surfaces |
| Function of fimbriae and pili | attachment to surface, bacterial conjugation and transformation, twitching and gliding motility |
| Function of flagella | swimming and swarming motility |
| function of endospores | survival under harsh environmental conditions |
| what is the cell envelope? | plasma membrane (innermost layer) and all exterior layers such as cell wall, capsid, slime layers |
| what is the function of the cell envelope | protection from osmotic pressure and maintenance of cell shape |
| cell envelope of gram pos bacteria | plasma membrane and thick exterior cell wall layer |
| cell envelope of gram neg bacteria | plasma membrane, thin cell wall, and exterior outer membrane forming a periplasmic space between the plasma and outer membrane |
| fluid mosaic model | membranes provide an environment in which membrane proteins "float" --> mobile in the membrane plane |
| phospholipids | bacteria change fatty acid composition of phospholipids to adapt to temp changes (higher temps --> becoem more saturated (rigid)) |
| Hopanes | sterol analogs of bacteria maintains membrane fluidity |
| peptidoglycan is made up of what components | carbohydrate component and peptide component |
| what are the carbohydrate components of peptidoglycan | N-acetylmuramic acid (NAM) and N-acetylglucosamine (NAG) |
| what are the peptide components of peptidoglycan | pentapeptide chains attached to NAM-carboxyl group as amides D/L-Ala, diamino acid, D-Glu building blocks peptide chains involved in cross linking glycan polymer |
| what are the two types of crosslinks between peptide chains | •direction connection of peptide chains •connection of peptide chains via peptide interbridges |
| what do both crosslinks require | diamino acids (contains amino group on alpha carbon and another one at end of R group) |
| what diamino acids are present in peptidoglycan | •L-lysine •mesodiaminoplimelic acid •D-ornithine |
| Gram positive bacteria structure | •thick peptidoglycan layer (more crosslinking, has mainly interbridges) • one plasma membrane • small periplasmic space with few proteins • has teichoic acid |
| what is the structure of teichoic acid and which type of bacteria is it found in | •made of phosphate, glycerol, and a side chain R --> phosphoglycerol (R may represent D-alanine, glucose, or other molecules) •found in gram pos bacteria |
| Gram negative bacteria | •thin peptidoglycan layer •two plasma membranes (inner + outer membrane) •large periplasmic space with secreted proteins |
| what does the outer membrane of gram neg bacteria consist of | lipopolysaccharides |
| what is the function of lipopolysaccharides | • negatively charged outer membrane surface • membrane stabilization • permeability barrier • host cell immune response • toxic reactions in host (lipid A) |
| protoplasts | gram positive bacterial cells without peptidoglycan |
| spheroplasts | gram neg bacteria cells without peptidoglycan |
| what happens if the cell wall formation is compromised by an antibiotic | bacterial cell loses its peptidoglycan layer and is prone to cell lysis |
| facilitated diffusion | • protein mediated transport of analytes along a concentration gradient • carrier or channel transport • no energy input • molecules continue to enter only as long as their concentration is greater on the outside |
| carrier facilitated transporter examples | uniporter or cotransporters |
| uniporter | move a single substance into the cell |
| symporter | both substances move in same direction |
| antiporter | two substances move in opposite directions |
| active primary transporter | transport of solute coupled to released energy of ATP hydrolysis |
| active secondary transporters (cotransporters/uniporters) | transport of solute coupled to potential energy of ion gradient |
| group translocation | transport of solute coupled to release of energy of solute phosphorylation |
| iron uptake | iron = important cofactor of metabolism (Fe3+ is very insoluble) bacteria produce siderophores to bind Fe3+ extracellularly and import the siderophore bound iron siderophores are important virulence factors fo pathogens to colonize hosts |
| 70S ribosomes are consist of what subunits | 50S and 30S |
| bacterial plasmids | • extrachromosomal, mostly circular DNA molecules • independent replication from chromosomal DNA • not essential to cell survival but can confer ecological advantages |
| conjugative plasmids function | transfer of DNA from one cell to another |
| function of R plasmids | carry antibiotic resistance genes |
| function of Col plasmids | produce bacteriocins, substances that destroy closely related species |
| function of virulence plasmids | carry virulence genes |
| function of metabolic plasmids | carry genes for enzymes |
| what are the three parts of bacterial flagella | • filament (filament protein arranged in helix) • hook • basal body |
| what occurs at the basal body | • where movement is generated • has different rings depending on if gram +/- |
| how does the flagella work? | MotA and MotB create a channel through which protons can flow (have pores to let protons flow through) thus causing the flagellum to rotate |
| bacterial endospores | • dormant bacterial cells • resistant to heat, radiation, and chemicals • forms during regular cell division |
| what causes endospore germination | • detection of nutrients by inner membrane receptors • breakdown of peptidoglycan and water uptake • enzyme activation |
| Component of the chain of infection | agent, virulence, exposure, dose, susceptibility |
| agent, virulence, exposure, dose, susceptibility | natural environmental location in which the pathogen normal resides (ex: soil, animal) |
| zoonosis | disease transmitted from animals to humans (ex: animal direct contact, animal products/waste) |
| indirect exposure (infection/transmission) | airborne, food contamination, surface contamination |
| direct exposure (infection/transmission) | human/animal contact, vector |
| what is the bacterial pathogen of anthrax | bacillus anthracis --> gram pos rod shaped bacterium • forming endospores |
| what is the usual reservoir of anthrax | soil, cattle, farm animals |
| how do organisms get infected by anthrax | • inhalation of airborne spores (dormant cells) • ingestion of spores on contaminated food • direct contact with infected animals (zoonosis)/humans |
| what happens when spores get into the body where its rich with waters, sugars, and other nutrients | they become active, the bacteria can multiply, spread out in the body, produce toxins, and cause severe illness and death |
| bacteria pathogen of lyme disease | borrelia burgdorferi --> gram neg spirochete bacterium |
| what is the usual reservoir of pathogens for lyme disease | rodents, deer |
| How does infection with Lyme disease occur | • ticks are vectors which gain B. burgdorferi from animal reservoirs such as rodents • nymph and adult ticks can transmit pathogens to humans via bite and blood exchange for 36-48hrs |
| Lyme disease is an example of what kind of infectious bacterial disease | zoonosis, vector borne bacterial infectious disease |
| Bacterial pathogen for the plaque | Yersinia Pestis --> non-motile gram neg rod shaped bacterium |
| how does infection with the plaque occur | bite of oriental rat flea and other flea species for infected rates |
| the plaque is an example of what kind of infectious bacterial disease | zoonic, vector borne bacterial infectious disease |
| What is the bacterial pathogen for Tuberculosis (TB) | mycobacterium tuberculosis --> gram pos rod shaped bacterium |
| what is the usual reservoir for M. tuberculosis | • human • non-human suspected reservoir: cattle, horses, cats, dogs |
| how does infection with tuberculosis occur | direct contain with a human with active TB disease |
| TB is an example of what kind of bacterial infectious disease | air borne transmission |
| bacterial pathogen of salmonellosis | Salmonella sp. --> gram pos rod shaped bacterium |
| usual reservoir for Salmonella sp. | humans or animals (intestines) • fowl, sheep, cattle, horses, dogs, cats, rodents, reptiles, birds, turtles |
| how does infection with salmonellosis occur | • eating contaminated food or drinking contaminated water (indirect) • touching infected animal waste (indirect) • touching infected animals (direct) |
| bacterial pathogen for cat scratch disease | bartonella hensalae --> gram neg rod shaped bacterium |
| what is the usual reservoir for B. hensalae | cats (zoonosis) |
| how does infection of cat scratch disease occur | • cat infection by cat flea bites • cat scratch and contact with infected cat feces |
| requirements for pathogens to survive in infected host | • suitable environment • nutrients • protection from host defense |
| virulence factors are employed to? | • find/establish environments and niches • evade host defense • acquire nutrients |
| Incubation period | time between pathogen entry and the development of signs and symptoms |
| prodromal period | period with signs and symptoms not allowing a diagnosis, patient can be contagious |
| illness period | severe disease stage with characteristic signs and symptoms, triggering host immune response • period for antibiotic treatment |
| convalescent period | recovery stage |
| pathogenicity island | virulence factor genes are often co-localized in a bacterial genomic region or in plasmids |
| how to distinguish pathogen from non pathogenic strains of the same species | pathogenicity island |
| characteristics of pathogenicity island | insertion of elements at 5' and 3' ends and different G-C content than genome |
| what are virulence factors | molecules that assist the bacterium to colonize the host at the cellular level |
| what are the three types of virulence factors | • cytosolic virulence factors • cell envelope • secreted virulence factors |
| cytosolic virulence factors | • adaptive metabolic, physiological, and morphological shifts • response to host immune stress |
| cell and envelope associated virulence factors | attachment and evading the host immune system |
| secreted virulence factors | • attachment • damage the host • establish suitable environment • protection against host immune systems |
| adherence and colonization factors | • extracellular pathogens attach to intracellular spaces •intracellular pathogens invade host cells |
| what is the first step in bacterial infection | host entrance and attachment |
| main attachment mechs | • pili & fimbriae • capsule (capsular polysaccharides) • lipopolysaccharides O-antigens (gram neg bacteria) • cells envelop proteins (often cell type specific interaction --> cause tissue specific attachment) • secreted polysaccharides |
| secreted polysaccharides as an attachment mech | • generation of attachment surface by secreted and cell wall bacterial glycosyltransferases • carbohydrate structures can module disease susceptibility |
| active invasion mechs | • attach on extracellular matrix of host tissues • degradation of carbohydrate protein complexes • disruption of host cell surface • secretion of reactive oxygen species (e.g. H2O2) --> damaged epithelial cells |
| what enzymes are secreted in the attachment on the extracellular matrix of host tissues that allows them to invade deeper tissues | • • hyaluronidase (carbohydrate degradation) by streptococcus sp. • collagenase (protein degradation) by clostridium sp. |
| what enzymes are secreted that degrade carbohydrate protein complexes | proteases |
| what enzyme is secreted that disrupts host cell surface | phospholipase C which binds to host cell surface and hydrolyzes phosphatidylcholine and sphingomyelin leading to membrane disruption |
| passive invasion mechs | skin wounds, lesions/breaks of epithelia, tissue damage by other organisms |
| exotoxins | secreted proteins to target specific cells and tissues (often very toxic) |
| Types of exotoxins | AB toxin --> two protein system |
| what does protein B of AB toxin do | binds to host cell receptor |
| what does protein A of AB toxin do? | enzyme which causes toxicity on or in host cells |
| diphtheria toxin | • protein A catalyzes ADP ribosylation of eukaryotic elongation factor 2 (eEF2) • AP ribosylation prevents mRNA translocation during translation by eEF2 in host cell ribosome |
| botulinum toxin | • most toxic compound • protein is a protease which cleaves SNARE proteins involved in release of neurotransmitters at synapses which results in vesicles not being able to fuse to the membrane and release the neurotransmitters • results in paralysis |
| Pore forming exotoxins | forms pore in membrane causing cytoplasmic contents to go out (low osmolarity) and water to come in causing swelling, host cell lysis, and death (high osmolarity) |
| what is secreted with pore forming exotoxins | protein monomers and synergistic peptides |
| Superantigens | non specific activate of host T cells by crosslinking MHC-II of macrophages with T cell receptors |
| what happens as a result of superantigens | releases a large amount of cytokines which results in an overstimulation of the immune system leading to inflammation, toxic shock, weakening the host and enables bacterial dissemination |
| Lipopolysaccharide Lipid A | • gram neg pathogens • bound to Toll-like receptor 4 on macrophages • release of high amounts of lipid A during a severe infection results in severe immune response, organ failure, sepsis |
| what are strategies to evade immune response | • prevention of detection • attach on host immune proteins • biofilms |
| how do bacteria prevent detection | • mucous production on bacterial capsule to prevent binding by immune cells • surface production • O-antigen changes • pili/surface protein changes |
| what surface proteins can be produced to prevent detection and what do they do | Protein M • binds immune system proteins and fibrinogen (clotting substrate) tightly thus evading phagocyte binding and immune response Protein A • binds antibodies on the heavy chain end which usually binds to phagocytes |
| O-antigen changes | gram neg bacteria can alter the length of polysaccharide chains of LPS can be changed to evade immune detection |
| how does attachment on host immune proteins allow bacteria to evade immune response | secretion of proteases to degrade immune proteins |
| what is a biofilm | clusters of bacteria that are attached to a surface and/or to each other and embedded in a self-produced matrix (proteins, polysaccharides, environmental DNA) |
| what are advantages of biofilms | • offers protection from host immune cells and proteins, shared nutrients and rapid exchange of plasmid DNA (slower metabolism makes bacterial pathogens more persistent) • improves resistance to antibiotics and host immune system during host colonization |
| what can host phagocyte attack on biofilm cause | tissue damage because host phagocytes detect and attempt to destroy biofilm cells but are unable to capture them so phagocytes release antimicrobial products that kill host cells but not biofilm cells |
| broad spectrum antibiotics | inhibition of both gram pos and neg bacteria |
| narrow spectrum antibiotic | inhibition of only a few genera of either gram neg or gram pos bacteria |
| bacteriocidal | can be usually administered in a dose which kills a bacterium |
| bacteriostatic | can be usually administered in a dose which prevents growth of a bacterium |
| when is there a benefit in administering a bactericidal antibiotic instead of bacteriostatic | when administering to immunocompromised patients, life threatening infections and surgical prophylaxis |
| characteristics of a beta lactam antibiotic | • feature a beta lactam ring (four membered cyclic amide) • ring fused to the beta lactam ring |
| reactivity of the ring | •beta lactam amide has no planar bond character due to the fused ring •strained ring system makes them more reactive than peptide bond amides --> more prone to nucleophilic attack to the lactam carbonyl group (open up the ring system to relieve strain) |
| mech of action for beta lactam drugs | • inhibit transpeptidase domains of penicillin binding proteins which catalyze the crosslinking of peptide chains of peptidoglycan during cell wall synthesis • mimic D-Ala-D-Ala substrate of penicillin binding protein |
| what type of inhibition does beta lactams have | irreversible |
| R group on beta lactam ring substituent has effect on what? | • acid stability and intact drug absorption in GI tract • stability against bacterial beta lactamase • drug concentration in blood • antibacterial activity |
| why is acid stability important | in acidic conditions the carbonyl of the R-acyl substituent can attack the beta lactam intramolecularly as a nucleophile, open the ring, and inactive the drug |
| what R groups increase acid stability in penicillin | electron withdrawing R group reduces nucleophilicity of the R-acyl carbonyl and thus increase acid stability of the drug allowing them to be more absorbed in the GI tract |
| how does the R group on beta lactam ring substituent affect stability against beta-lactamase | larger R group increases resistance to beta lactamases |
| what do beta lactamases do | serine proteases which catalyze hydrolysis of beta lactams --> inactivates beta lactams |
| how does the R group of beta lactam ring affect drug concentration in blood | less hydrophobic R groups decrease binding of penicillin to plasma proteins thus increasing blood plasma drug concentration |
| how does the R group affect antibacterial activity | can change the antibacterial spectrum of penicillin • more hydrophilic R enables transport through gram neg outer membrane porins making them more of a broad spectrum antibiotic |
| structure of vancomycin | hexapeptide core structure with multiple cross linked aromatic side chains and a disaccharide glycosyl group |
| mech of action of vancomycin | binds to D-Ala-D-Ala portion of peptidoglycan peptide chains and thereby prevents peptide chain cross linking during cell wall synthesis |
| pharmacology of vancomycin | • low oral bioavailability - administered as IV infusion (oral use for GI tract infections) •main use against gram pos bacteria (lower absorption by gram neg) • low resistance (antibiotic of last resort against antibiotic resistant bacterial pathogens_ |
| structure activity relationship for vancomycin | vancomycin analogs with hydrophobic modifications to the vancomycin glycosyl groups can also disrupt bacterial cell membrane in addition to cell wall synthesis inhibition |
| structure of daptomycin (lipopeptide) | 12 aa cyclic peptide with charged amino acids in the peptide macrocycle and at atty acid chain at the N terminus |
| mech of action of daptomycin | • disruption of bacterial cell membranes by intercalation into lipid bilayer, oligomerization and pore formation • membrane depolarization |
| pharmacology of daptomycin | • peptide --> lower oral bioavailability so usually administered as IV infusion • main use against gram pos bacteria •low resistance |
| Porin in outer membrane | central hydrophilic pore that enables passive transport of hydrophilic molecules such as nutrients but also some antibiotics |
| which antibiotics can pass through porins in gram neg bacteria | beta lactams, tetracyclines, and aminoglycosides |
| structure of aminoglycosides | • 1,3-diaminoinosital as core structure with 2-3 sugar groups added to it via diverse glycosidic bonds • 600-800 Da molecule weight |
| mech of action of aminoglycosides | • bacteriocidal • bind to 30S ribosomal subunit close to P-site impairing proof reading function at P-site |
| what results with use of aminoglycosides | binding at 30S subunit results in mistranslation of mRNA codons at P site leading to formation of non sense membrane proteins which leads to membrane rupture |
| Pharmacology of aminoglycosides | • not orally bioavailable • oral drug for GI tract infection • topical application (e.g. Neosporin) • broad spectrum against aerobic bacteria |
| aminoglycoside has a drug-drug interaction with what type of antibiotic | beta lactams --> inactivates both drugs by aminoglycoside mediated opening of beta lactam |
| how is aminoglycosides transported into gram neg bacteria | after binding to O-antigen polysaccharides it gets transported into the bacteria via porins |
| macrolide structure | • large lactone ring with usually 1-2 glycosyl group(s) • weakly basic (pka ~8) • acid instability due to intramolecular attack at C9-carbonyl by C6-hydroxy group |
| what are ways to improve acid stability in macrolides | • acid protective tablet coating • removal of C6-hydroxy • removal of C9-ketone • acid insoluble macrolide formations |
| Mech of action for macrolides | • bacteriostatic at pharmacological concentrations • binding to 23S rRNA in 50S subunit near peptide exit tunnel • inhibits peptide chain synthesis beyond several amino acids resulting in generation of incomplete proteins |
| pharmacology of macrolides | • narrow spectrum mainly against gram pos bacteria • mainly used to treat infection in respiratory tract |
| structure of tetracyclines | •dimethylated amine on A ring required for activity •chelation of polyvalent metal ions causes formation of insoluble salts - no administration with Calcium rich food •looks like four rings connected to each other with the left most ring being a benzene |
| mech of action of tetracyclines | • bind to 30S subunit at A site and block tRNA binding -> blocks protein synthesis • rRNA binding requires magnesium |
| pharmacology of tetracyclines | • broad spectrum but rarely first choice in antibacterial therapy • bacteriostatic |
| structure of linezolid | • synthetic antibiotic • contains ring with O and Nitrogen and a F off of a benzene |
| mech of action of linezolid | bind to 50S subunit blocking formation of initiation complex with 30S subunit, mRNA and initiation factors --> blocks protein synthesis |
| pharmacology of linezolid | • narrow spectrum --> gram pos bacteria • bacteriostatic • orally bioavailable |
| Structure of Retapamulin | • semisynthetic fungal natural product (diterpene core structure) • has an eight membered ring |
| mech of action of Retapamulin | • bind to 50S subunit and inhibits peptidyl transferase -> blocks peptide bond formation • different binding site than macrolides |
| pharmacology of Retapamulin | • bacteriostatic • used for skin infections (topical application) |
| Sulfonamides structure | • synthetic antibiotics with sulfonamide group (SO2NH2) • Prontosil is active in vivo but not in vitro (cleavage of azo group to sulfanilamide by liver enzymes required for activity --> prontosil = prodrug) |
| Mech of action of sulfonamides | • inhibit dihydropteroate synthase in folic acid biosynthetic (cofactor for thymidine biosynthesis) • substrate mimic of p-aminobenzoic acid • competitive inhibitor |
| Trimethoprim structure | • synthetic antibiotic • folate mimic |
| Mech of action of trimethoprim | • inhibits dihydrofolate reductase in folic acid biosynthesis (cofactor for thymidine biosynthesis) • substrate mimic of dihydrofolic acid pterin ring --> competitive inhibitor |
| trimethoprim pharmacology | • orally bioavailable • usually administered in combination with a sulfonamide antibiotic --> reduced resistance |
| folic acid biosynthesis pathway only available in humans or bacteria | only bacteria can biosynthesize folic acid |
| Quinolones structure | • synthetic antibiotic • N-alkylated carboxy-4-pyridone core structure |
| Mech of action of quinolones | • inhibition of bacterial DNA gyrase (topoisomerase) during replication and transcription • no inhibition of human topoisomerase at clinical doses |
| Quinolones pharmacology | • bacteriocidal • broad spectrum as newest approved drug analogs • chelation of polyvalent metals by pharmacophore results in insolubility --> no metal drugs or calcium rich food taken with quinolones |
| Rifamycin structure | • Naphthalene core |
| Mech of action of Rifamycin | • inhibition of bacterial RNA polymerase --> inhibits RNA biosynthesis • Naphthalene core binds to aromatic amino acids and chelates Zn2+ (cofactor of RNA polymerase) |
| Rifamycin's pharmacology | • broad spectrum but less effective against gram neg bacteria due to poor outer membrane transport • particularly effective in the treatment of tuberculosis |
| Intrinsic resistance | • mutations of genes in the bacterial genome or plasmids leads to generation of resistance genes • resistance genes are transferred to next generation through vertical gene transfer |
| Acquired resistance | resistance genes are transferred between bacteria through mobile genetic elements in horizontal gene transfer (most common element: plasmids) |
| What are general resistance mechs | • reduced drug influx • modifications of drug targets • inactivation of drugs • increased drug efflux |
| what are ways to reduce drug influx | •outer membrane of gram neg bacteria --> intrinsic resistance barrier against vancomycin, daptomycin •change in membrane lipid composition --> changed drug permeability •changed porin selectivity •biofilm formation --> decreased drug permeability |
| what are ways to modify protein targets and what are some examples | • amino acid substitutions in active site • PBPs with different active site --> no beta lactam drug binding • D-Ala-D-Ala → D-Ala-D-Ser/D-Ala-D-Lac-Peptidoglycan → vancomycin not able to bind |
| what are ways to modify the membrane and what are some examples | • lipid substitution • Change in polarity in polar groups of cytoplasmic membrane lipids → change from phosphatidylglycerol phospholipids to lysyl-phosphatidylglycerol lipids • Reduced daptomycin binding (Ca2+ dependent membrane binding) |
| What are ways to modify RNA binding sites and example of resistance against | methylation of rRNA at macrolide binding site by ribosomal methyltransferases prevent antibiotic binding |
| what are ways to bypass targets of antibiotics | Production of additional versions of target to bypass original target during antibiotic presence (RNA polymerase with less affinity for rifamycin) |
| what mechs are there to inactivate drugs | • drug degradation (beta-lactamases) • drug modification --> Acetylation, phosphorylation, adenylation of drug molecules leading to inactivation (can modify aminoglycosides to deactivate) |
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