microbiology final

list some ways infections can influence the microbiota

list some ways infections can influence the microbiota

diarrhea reduces overall numbers of gut microbiota, intestinal pathogens occupy host binding sites and alter available nutrients, inflammation can benefit pathogens more than normal microbiota

parasite

an organism that benefits while it causes damage to the host

primary pathogens

cause disease in healthy hosts

opportunistic pathogens

cause disease only in comprised hosts or after entering unprotected sites

reservoirs

animal, bird, or arthropod that normally carries the pathogen without showing symptoms

ID50

infectious dose, amount of virus to infect 50% of the host

LD50

lethal dose, amount of virus to kill 50% of the host

direct infection

involves direct contact between people or reservoirs

indirect infection

transmission by “vehicles” such as inanimate objects

horizontal transmission

direct or indirect contact with formites or vehicles

vertical transmission

passage from a mother to her fetus during pregnancy or birth

portals of entry (5)

mouth, respiratory tract, conjuctiva and mucous membranes, wounds, injuries, and skin lesions, parental route - direct injection into blood stream

role of immunopathogenesis in disease pathology

immune response to a pathogen is a contributing cause of pathology and disease

roles of virulence factors (5)

enter a host, find their niche, avoid normal host defenses, multiply, transmit to a new susceptible host

molecular Koch’s postulates that confirm the identity of a pathogenicity gene (3)

phenotype under study should be associated with pathogenic strains of a species, specific inactivation of the virulence genes should reduce its effects and isolate the gene, reversing or replacing the mutated gene should restore pathogenicity

how are proteins involved in pathogenesis

many proteins are secreted by type III systems in pathogenicity islands

pathogenicity islands

clusters of virulence genes in bacterial pathogens that encode virulence functions and are horizontally transmitted

indicators of pathogenicity islands

unique GC/AT ratio, linkage to a tRNA gene, association with genes homologous to phage/plasmid genes

role of horizontal gene transfer in pathogen evolution

genomic sequencing has proven that epidemics are caused by new strains of the same pathogen rather than an old strain reemerging

viral and bacterial host attachment mechanisms

adhesin, capsid or envelope proteins (virus), pili or nonpilus proteins (bacteria)

type I pili assembly

adhere to carbohydrates on host membranes, produce static attachment to the host cell, grow from the outer membrane of certain gram-negative bacteria

type IV pili assembly

involved in “twitching motility”, produce dynamic attachment via assembly and disassembly, grow from inner membrane of many gram-negative bacteria

how do differences in host susceptibility occur

immunocompetence and receptor availibility

role of biofilms in infections

enable persistent adherence, resistance to host defenses, and tolerance to antimicrobial agents

exotoxins

proteins produced and secreted by various types of bacteria that kill host cells and unlock their nutrients

endotoxins

a part of a lipopolysaccharide of gram-negative bacteria and hyperactivate host immune systems to harmful levels

functional categories of bacterial exotoxins (9)

plasma membrane disruption, cytoskeleton alterations, protein synthesis disruption, cell cycle disruption, signal transduction disruption, cell cycle disruption, cell-cell adherence, vesicular traffic, inhibit exocytosis, superantigens

hemolysins

membrane-disrupting toxin that lyses red blood cells

leukocidins

membrane-disrupting toxin that lyses white blood cells

AB exotoxins

consists of a ring of B subunits and a central A subunit that work together to disrupt host cell functions, A subunit is the toxicity-associated factor, B subunit binds to the host cell and delivers the A subunit

mechanisms of host cell cAMP disruption by bacterial exotoxins

cholera toxins target a host cell with A subunit ADP-ribosylates and can cause sharp increases in cAMP levels, resulting in ion transporters carrying water out of the cell and causing diarrhea

toxins that disrupt protein synthesis (2)

shiga toxin, diphtheria toxin

shiga toxin

exotoxin produced by shigella and e. coli whose A subunit cleaves the 28S rRNA in ribsomes to cause acute kidney failure

diphtheria toxin

exotoxin produced by corynebacterium diphtheriae twhose A subunit ADP-ribosylates eukaryotic elongation factor 2, causing cell death and pseudomembrane formation in the trachea

type II secretion

a modification of the same system used for type IV pilus biogenesis with extendable and retractable secretion structures that secrete proteins

type III secretion

reengineered flagellar synthesis mechanism normally located within pathogenicity islands that typically is triggered by cell-cell contact and injects proteins from the bacterial cytoplasm into the host cell through a molecular syringe

pore-forming proteins

exotoxins that disrupt host cell membranes by inserting themselves into the membrane by binding cholesterol and membrane receptors

phospholipase enzymes

exotoxins that disrupt host cell membranes by hydrolyzing phospholipids into fatty acids

type IV secretion system

evolutionary modification of a conjugation pilus that secretes proteins and sometimes proteins and DNA directly from the cytoplasm or periplasm

bacterial toxin secretion system 1

SecA dependent, one effector per system (E. coli alpha hemolysin)

bacterial toxin secretion system 2

SecA dependent, similar to type IV pili (pseudomonas aeruginosa exotoxin A)

bacterial toxin secretion system 3

SecA independent, multiple effectors secreted, syringe mechanism injects effectors into target cells (Yersinia Yop proteins)

bacterial toxin secretion system 4

related to conjugational DNA transfers, multiple effectors secreted, some systems inject effectors into target cells (B. pertussis toxin)

bacterial toxin secretion system 5

autotransporter, SecA dependent to periplasm, self-transport through outer membrane, one effector per system (Gonococcal)

bacterial toxin secretion system 6

related to phage tails, single effector, harpoon mechanism (burkholderia)

steps of toxin secretion through Type II secretion system

proteins secreted into periplasm, get folded, secreted through outer membrane pore

examples of Type III secretion system

salmonella, yersinia, shigella, escherichia

mechanisms pathogens use to determine their location

two-component signal transduction systems that monitor magnesium and pH levels and quorum sensing to detect exotoxins made by other cells

ways pathogens avoid extracellular immune detection

secrete thick capsule, produce proteins that bind to antibodies, induce apoptosis of phagocytes, alter surface antigens

strategies intracellular pathogens use to prevent phagolysosome induced death

learn to grow in acidic conditions of the phagolysosome, prevent phagosome-lysosome fusion, escape the phagosome

mechanisms used by pathogens to avoid intracellular immune detection

mimicry by changing antigens, flipping cytokine profiles, stopping apoptosis, redirecting host ubiquitylation signals that tag proteins for destruction

salmonella virulence factors

type III secretion systems invade host cell and replicate within the host cell, has 14 pathogen islands

genomic tools that have proven pathogen biology

genomic sequencing and bioinformatic analysis can identify potential pathogenicity islands and virulence genes, compares sequences of virulent and attenuated strains, and reveals how to grow obligate intracellular pathogens in the lab

how to use RNA sequencing to understand host-pathogen interactions

monitors pathogens’ transcripts during infection and views the host’s transcriptional response to it

fluorescence resonance energy transfer

identifies which host cells have been targeted by the pathogen proteins by constructing translational fusion between a gene encoding a bacterial effector protein and a ß-lactamase gene, once expressed a fusion protein can be translocated from the pathogen directly into host cells using one of the secretion systems.

folliculitis symptoms and causative agents

(skin disease) boils

staph aureus

necrotizing fasciitis symptoms and causative agents

rapidly progressive cellulitis

staph aureus

strep pyogenes

clostridium perfringens

scalded skin syndrome symptoms and causative agents

peeling skin on infants, systematic toxin

Staph aureus (G+ cocci)

rubella symptoms and causative agents

discolored, pimply rash, mild disease unless congenital

rubella virus

measles symptoms and causative agents

severe disease, fever, conjunctivitis, cough, rash

rubeola virus

chickenpox and shingles symptoms and causative agents

discolored lesions

herpesvirus

varicella-zoster

nosocomial infections

infections caught from the hospital

staph aureus vs strep pyogenes

s. aureus - gram positive organism that is normally found in nostrils

s. pyogenes - gram positive coccus best known for causing sore throats and immunological sequelae (ie. rheumatic fever) and can also cause necrotizing fasciitis and cellulitis

fungal respiratory infection

typically requires immunocompromised host to cause disease

viral respiratory infections

localized, influenza and rhinovirus, SARS, RSV

bacterial respiratory infection

most deadly, mycobacterium tuberculosis is leading cause of death by microbe

anthrax symptoms and causative agents

hypotension, respiratory failure

bacillus anthracis

whooping cough symptoms and causative agents

violent cough inhalation “whoop”

bordetella pertussis

pneumonia symptoms and causative agents

sore throat, chest pain, nonproductive cough

pseudomonas aeruginosa

mycoplasma pneumoniaeRSV

tuberculosis symptoms and causative agents

cough, bloody sputum, fatigue, weight loss

mycobacterium tuberculosis

RSV disease symptoms and causative agents

cough, chest pain

respiratory syncytial virus

severe acute respiratory syndrome symptoms and causative agents

cough, chest pain

SARS virus

why is tuberculosis a reemerging disease

primary tuberculosis is typically latent/dormant as the body walls the bacilli off in a granuloma and secondary is caused by reactivation of the pathogen (typically in immunocompromised people)

infection defense mechanisms of the lung

mucociliary escalator

mucociliary elevator

cilia moves mucus out of the respiratory tract into the mouth, where inhaled respiratory infections caught in the mucus will be swallowed and killed in stomach acids. as long as pathogens can’t stick to the lung cilia or wall, infection will not occur

most common causes of diarrheal diseases

viruses, specifically rotavirus, and salmonella enterica and campylobacter

osmotic diarrhea

water absorption in intestines

secretor diarrhea

secreted water in intestine exceeds absorption

inflammatory diarrhea

the epithelium gets disrupted and serum and blood are released into the intestine, destroying the intestinal epithelium

motility-related diarrhea

any condition that increases the time necessary for nutrients and water to be exposed to the intestinal epithelium for absorption

gastritis

inflammation of the stomach lining (ulcers)

gastroenteritis

nonspecific term for any inflammation along the GI tract

enteritis

inflammation mainly of the small intestine

enterocolitis

inflammation of the colon and small intestine

colitis

inflammation of the colon (large intestine)

best treatment plan for diarrheal disease patients

rehydration therapy

symptoms and causes of food poisoning

immediate diarrhea and/or vomiting

staph aureus

clostridium difficile

caused when antibiotic treatment of GI diseases causes competing bacteria to die and allows pathogen to thrive. can overgrow and cause pseudomembranous and may lead to ulcerative colitis and/or sepsis

enterohemorrhagic E. coli (EHEC)

do not invade intestinal cells, attachment and effacing lesions produced cause bloody stool

effects of diarrhea in gut microbiome

reduces diversity of microbiome

heliobacter pylori stomach survival

secretes enzyme urease, which converts urea into ammonia to neutralize stomach acids, followed by enzymes collagenase and mucinase to soften the mucous lining of the stomach and allow for the bacteria to burrow into the protective mucous layer where they’ll grow and divide, damaging the tissue

disease caused by heliobacter pylori

gastric cancer

Hep A (HAV)

-sense ssRNA virus that takes the fecal-oral route and is not a chronic illness

hep B (HBV)

dsDNA virus in the blood that is a chronic illness

hep C (HCV)

+sense ssRNA virus in blood that is chronic

urinary tract organ system

kidneys, uterus, urinary bladder, urethra

ways that UTI-causing bacteria enter bladder or kidney (4)

infection from urethra to bladder, deposition of bacteria from blood to kidney, descending infection from kidneys, ascending infection to kidneys

etiological agents of UTIs

uropathogenic E. coli, klebsiella, proteus, pseudomonas, enterobacter, certain gram positive bacteria and fungi

difference between uropathogenic e. coli and other strains of e. coli

the other strains cause GI disease

gonorrhea symptoms and causative agents

purulent discharge, burning urination, potential sterility

neisseria gonorrhoeae (G-)