Lecture 5 Pathogenesis, Role, Diagnosis, Drugs (E1) Flashcards

Ch 14, 15, 16, 17

1
Q

Bacterial Virulence

A

Causes disease:
Attachment
Toxins
Immune escape

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2
Q

Pathogenicity Islands

A

group of genes typically with coordinated expression that leads to disease (strains of bacteria)

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3
Q

Disease

A

Combination of bacterial virulence and host response

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4
Q

Innoculum

A

required number of bacteria to establish infection

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5
Q

Normal Flora

A

in the right place, no problem
wrong place, opportunistic

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6
Q

Microbial acquisition

A

Getting the “normal flora”
Birth canal
Food (breast, bottle)
Breathing
Natural succession
-Lactobacilli (mouth, intestines, vagina during reproductive years)
-Coliforms (mouth, intestines)
-Anaerobes (intestines)

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7
Q

Microbial impact

A

Normal flora
Biological success (their “perspective”)
Microbial antagonism (“good” bacteria compete for space and resources on the host)
Can improve host nutrition (e.g Vit-K, short chain-Fatty Acids)- Metabolism of good bacteria
Immune stimulation/regulation
Also have potential negative impacts (opportunistic infection, immune dysregulation)

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8
Q

Sterile Sites

A

heart, liver, Kidneys, Bladder, Brain, Spinal Cord, Bones, Ovaries, Testes, Sinuses (upper), Ear (Middle, inner)
Eye (Internal), Muscles, Glands (internal)

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9
Q

Opportunistic infection

A

Normal flora in the wrong place

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10
Q

Susceptibility

A

Weaken Host defenses
Old age and extreme youth
Genetic defects in immunity, and acquired defects in immunity (AIDS)
Surgery and organ transplants
Underlying disease: cancer, liver malfunction, diabetes
Chemotherapy/ immunosuppressive drugs
Physical and mental stress

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11
Q

Portals of Entry

A

Typically where something is non-moving
Skin
Gastrointestinal tract
Respiratory Tract
Urogential Tract

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12
Q

Attachment to the host

A

Fimbriae
Capsules
Receptors
Hook or by crook

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13
Q

Surviving the Host

A

Anti-Phagocytic factors
Capsules
Leukocidins
Virulence Factors (Toxins/Exozymes)

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14
Q

Disease (causing damage to host)

A

Virulence factors (Toxins/Exozymes)
Inflammation by the host

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15
Q

Portals of Exit

A

Same as portals of entry

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16
Q

Biofilms

A

Community of bacteria
Quorum sensing- What makes bacteria difficult
Dental plague
Protection from immune system, antibiotics-have trouble getting through

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17
Q

Bacterial Adhesions

A

Bacterial structures used to attach to host cell
Fimbriae (pili)- typically the tips have an adhesion molecule (sugar molecules on the end, bind to lectins)- host cell specificity
Blood group antigens
Some adhesins bind to cell oligosaccharide receptors
Some adhesins bind to cell proteins

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18
Q

Host receptors

A

Fibrinogen
Extracellular matrix components
d-Mannose
etc

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19
Q

Invasion

A

Active avoidance (our immune system) or destruction of barriers (physical, chemical, immune)
Most bacteria cannot penetrate intact skin, however, most skin has micro-abrasions so can be breached
Induce inflammation- host response, breaks its own barriers
Block phagocytosis (even though this is our go to)- Streptococci, Staphylococci
Encourage Phagocytosis- Salmonella, Yersinia (Engulfed, to avoid our immune system, able to survive)

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20
Q

Secretory Systems

A

Sec
Tat
Type I-VII
Function- getting into your cells

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21
Q

Exoenzyme

A

Proteases, Lipases, Glycosylases (secreted outside)

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22
Q

Exotoxin

A

Toxins that knock out a host enzyme
Secreted enzymes or proteins that alter function/kill a host cell (usually knockout key enzymes)
Ex: Tetanus, Clostridium, Diptheriae, Cholera

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23
Q

Type A-B Toxin

A

Heterodimeric Toxins
A- Action component
B- Receptor binding

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24
Q

Superantigen

A

T-cell activation (cytokine storms)
release of large quantities of IL-1, IL-2, IL-6, INF-y, TNF-a, Chemokines (release systemically)
Cause life threatening fever, shock, rash, autoimmunity
Staphylococcus toxic shock syndrome

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25
Diptheria toxin (A-B)
Target Cell Receptor- Growth factor receptor precursor Biological Effects- Inhibition of protein synthesis, cell death
26
Anthrax toxin (A-B)
Target Cell Receptor- Tumor endothelial marker-8 (TEM-8); capillary morphogenesis protein 2 (CMG2) Biological Effects- EF + PA: increase in target cell cAMP level, localized edema; LF+PA: death of target cells and experimental animals
27
Tetanus toxin (A-B)
Target Cell Receptor- Polysialoganglio sides plus 15-kDa glycoprotein (co-receptors) Biological Effects- Decrease in neurotransmitter release from inhibitory neurons, spastic paralysis
28
Botulism Toxin (A-B)
Target Cell Receptor- Polysialogangliosides plus synaptotagmin (co-receptors) Biological Effects- Decrease in peripheral presynaptic acetycholine release, flaccid paralysis
29
Cholera Toxin (A-B)
Target Cell Receptor- Ganglioside (GM) Biological Effects- Activation of adenylate cyclase, increase in cAMP level, secretory diarrhea
30
Lipid A Toxicity (acute response-binding events)
Lipopolysaccharides in Gram Negative, Induces strong acute-phase response 1. Acute phase response- fever, leukocytosis/leukopenia, disseminated (all around body) intravascular coagulation (DIC), hypotension, Shock and death 2. FDA limit 3. Binding events: Lipid binding protein (LBP, serum) Transfers to CD14 (CR, cell membrane)- MD2 associated with TLR4 which then sends signal to interior cell (acute response Triggered Event(direct or indirect): Production of cytokines LPS activates macrophages to enhanced phagocytosis and cytotoxicity Activation of the complement cascade(C3a, C5a) Histamine, neutrophil chemotaxis (pus) Activation of the coagulation cascade (Factor XII)
31
Granuloma
Mycobacteria
32
Autoimmunity
Strptococci pyogenes, anti-M-protein (during inflammation B-cells attack, but we have similar heart protein so we attack ourselfs)
33
Immune Complex
Chlamydia, Treponema, Borrelia, Streptococci
34
DIC
DIC thrombosis- Disseminated Intravascular coagulation (DIS)
35
Antibiotics
Range of activity of an antimicrobial against bacteria. A broad-spectrum antibacterial drug can inhibit a variety of gram(+) and gram(-) bacteria, whereas a narrow-spectrum drug is active against a limited variety of bacteria
36
Penicillins
Discovered by Fleming Block cross-linking of peptidoglycan (Transpeptidase) All have Beta-lactam ring Different spectra of action Resistance due to bacterial Penicillinases; (beta-lactamases)
37
Macrolides
are a class of drugs used to manage and treat various bacterial infections. Azithromycin, clarithromycin, and erythromycin are commonly used to treat infections like pneumonia, sinusitis, pharyngitis, and tonsillitis
38
Aminoglycosides
Binds 30S subunit of ribosome (irreversible?) Distorts the ribosome Errors translation Derived from Streptomycin and Micromonospora Neomycin (Neosporin Ointment) Relatively broad spectrum because they inhibit protein synthesis(good, still has toxicity problems)
39
Cephalosporins
Different ring structure and R groups than Penicillins Derived from Fungus Acremonium Block cross-linking of peptidoglycan All have beta-lactam ring (less susceptible to penicillinases) Different spectra of action (generations) Helps against G(-) outer membrane Broad-spectrum Cause fewer allergic reactions (penicillinases (hapten))
40
Tetracyclines
Binds 30S ribosome subunit Inhibit Protein Synthesis Blocks the A site on the ribosome (where the tRNA comes in) Prevents tRNA entry Reversible reaction Bacteriostatic Broad spectrum
41
Target Proteins
Goal of antimicrobial drugs -Disrupt the cell processes or structure of bacteria, fungi, and protozoa -or Inhibit virus replication Most interfere with the function of enzymes required to synthesize or assemble macromolecules or destroy structures already formed Drugs should be Selectively Toxic- They kill or inhibit microbial cells without damaging host tissues (macromolecules, proteins, nucleic acid)
42
Combination Therapy
Combinations of antibiotics that may be used to (1) broaden the antibacterial spectrum for empirical therapy or the treatment of polymicrobial infections, (2) prevent the emergence of resistant organisms during therapy, and (3) achieve a synergistic killing effect
43
Antibiotic synergism
Combinations of two antibiotics that have enhanced bactericidal activity when tested together compared with the activity of each antibiotic alone
44
Antibiotic antagonism
Combination of antibiotics in which the activity of one antibiotic interferes with the activity of the other (e.g. the sum of the activity is less than the activity of the most active individual drug)
45
Bacteriostatic
Antibiotic that inhibits the growth of bacteria but does not kill
46
Bactericidal antibiotic
Antibiotic that kills bacteria
47
Minimum inhibitory concentration(MIC)
Determined by exposing a standardized suspension of bacteria to a series of antimicrobial dilutions. The lowest antibiotic concentration that inhibits the growth of the bacteria is the MIC- what we need to achieve
48
Minimum bactericidal concentration (MBC)
Determined by exposing a standardized suspension of bacteria to a series of antimicrobial dilutions. The lowest antibiotic concentration that kills 99.9% of the population is referred to as the MBC
49
Beta-Lactamase
An enzyme that hydrolyzes the beta-lactam ring in the beta-lactam class of antibiotics, thus inactivating the antibiotic. The enzymes specific for penicillins, cephalosporins, and carbapenems are the penicillinases, cephalosporinases and carbapenemases, respectively Degrades penicillin
50
Targets of Antimicrobials
Cell wall inhibitors- Block synthesis and repair of peptidoglycan Cell Membrane- Cause loss of selective permeability (Polymyxins, Daptomycin) DNA/RNA- Inhibit replication and transcription; Inhibit gyrase (unwinding enzyme) (Quinolones, Inhibit RNA polymerase, Rifampin)-Very few drugs Protein synthesis inhibitors acting on ribosomes (site of action 50s, 30s and both) Folic acid synthesis- Block pathways and inhibit metabolism (Sulfa drugs)
51
Plasmid mediate resistance and mutations
Ways microbes have built drug resistance Plasmid- Acquisition of entire new genes or sets of genes via transfer from another species (plasmids, called resistance (R) factors) Spontaneous mutations in critical chromosomal genes
52
Porins (Gram (-))
Porins allow for the passive diffusion of water, ions, and other small molecules. They also help maintain osmolarity, transport nutrients and salts, and contribute to virulencePorin expression is regulated by several mechanisms, including β-barrel assembly machinery and lipopolysaccharide binding. Antibiotic resistance Adaptations that reduce the influx of compounds through porins can contribute to the emergence of antibiotic resistance
53
B-Lactam Ring
Crucially part of penicillin, screws up cross-linking in the cell wall
54
Efflux pumps
are transport proteins involved in the extrusion of toxic substrates (including virtually all classes of clinically relevant antibiotics) from within cells into the external environment. These proteins are found in both Gram-positive and -negative bacteria as well as in eukaryotic organisms.
55
Cephalosporin generations
1st Generation more gram positive 2nd 3rd 4th 5th Generation more gram negative
56
Carbapenems
An enzyme specific the penicillinases
57
Vancomycin
Inhibits cross-linkage of peptidoglycan layers
58
MRSA
Methicillin-resistant Staphylococcus aureus (MRSA) infection is caused by a type of staph bacteria that's become resistant to many of the antibiotics used to treat ordinary staph infections
59
CA-MRSA
Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is a type of MRSA infection that can affect anyone, but some people are at higher riskMRSA infections in healthy people who have not been hospitalized or had a medical procedure (such as dialysis or surgery) within the past year
60
Rifampin
Inhibition of Nucleic Acid Synthesis -Prevent transcription by binding DNA-Dependent RNA polymerase This is a difficult target because the process is well conserved (similar process and enzymes for most life forms) Specific for bacteria- favorable therapeutic index Prevents elongation of transcript after initiation Useful drug for tuberculosis Resistance can develop quickly
61
Amphotericin-B
an antifungal used to treat fungal infections in neutropenic patients, cryptococcal meningitis in HIV infection, fungal infections, and leishmaniasis binds sterols in cell membranes with a higher affinity toward ergosterol than mammalian cholesterol. As the concentration of the drug increases in organs such as the kidney, it begins to bind cholesterol in mammalian membranes, leading to nephrotoxicity
62
Flucytosine
may cause decreased kidney function and liver problems. In addition, this medication may decrease bone marrow function. This serious, possibly life-threatening side effect may lead to a low number of blood cells such as red cells, white cells, and platelets. -used in combination with other medicine (eg, amphotericin B) to treat serious fungus infections, including Candida infections (eg, septicemia, endocarditis, urinary tract infections) or Cryptococcus infections (eg, meningitis, lung infections) enters the fungal cell via cytosine permease; thus, flucytosine is metabolized to 5-fluorouracil within fungal organisms. The 5-fluorouracil is extensively incorporated into fungal RNA and inhibits synthesis of both DNA and RNA
63
Tetracycline
Inhibition of Protein synthesis- Prevent polypeptide elongation at 30S ribosome Blocks the A site on ribosome (where tRNA comes in) Prevents tRNA entry REVERSIBLE reaction Bacteriostatic Broad spectrum
64
Erythromycin
(Some people took for allergies/no tired) Large lactone ring with sugars attached relatively broad-spectrum Fairly low toxicity (heart arrythmyia with Seldane) Blocks protein synthesis by attaching to the 50S ribosome subunit Mycoplasma pneumonia, legionellosis, Chlamydia infections, pertussis, diphtheria
65
Tuberculosis Therapy
Using Rifampin, Binds to bacterial RNA polymerase mRNA sythesis
66
Isoniazid
Disruption of cell wall- Inhibits mycolic acid synthesis
67
Sulfamethoxazole
Often given with Trimethoprim, One of the primary treatments for Pneumocystis (carinii) Jiroveci pneumonia (PCP) in AIDS patients
68
Trimethoprim
Antimetabiolite- Inhibits dihydrofolate reductase and disrupts folic acid synthesis Sulfa drug THF is an important co-enzyme (we need but get in food, bacteria synthesize)- folic acid
69
Fluoroquinolones
DNA Replication- Few clinical drugs affect polymerization Mechanisms are conserved: lead to toxicity DNA gyrase inhibitors (DNA unwinders)