path micro 3

Diphtheria pathogen

Corynebacterium diphtheriae, gram positive rod, Chinese letter formation growth

Diphtheria encounter

HUMANS, asymptomatic carriage in oropharynx or skin

Diphtheria entry

C. Diphtheria is generally acquired through inhalation of contaminated respiratory droplets.

Diphtheria spread

none, remains local infection of oropharynx

Diphtheria multiplication

extracellular in the oropharynx, remain in clumps after multiplying, forming a palisade layer

Diphtheria damage

bacteria produces an exotoxin that inhibits translation. This results in the accumulation of a pseudomembrane on the tonsils or pharynx.

Diphtheria diagnosis

based on characteristic pseudomembrane. diagnostics can take up to a week. organisms can be cultured from samples on blood agar and colitistin naldixic acid agar, a selective media. microscopy is not effective.

Diphtheria outcome

treated with antibiotics, antitoxin and vaccination

Diphtheria

2-4 day incubation causes sore throat, fever, and malaise. Bull’s neck. Pseudomembrane and swelling of epiglottis and tonsils can lead to resp. blockage.

Diphtheria in healthy adults

generally cleared by immune system in 1 week.

Diphtheria in immunocompromised.

toxin secreted causes cardiac and neurological symptoms.

Diphtheria toxin

AB toxin that binds to heparin-binding epidermal growth factor (used for tissue growth and regeneration). Toxin is taken in via endocytosis, the vessel acidifies and releases A subunit from B subunit. A subunit binds EF-2 (elongation factor) so that it can no longer interact with ribosome. Toxin from temperate bacteriophage.

Diphtheria treatment

penicillin or erythromycin, antitoxin to neutralize toxin, also immunized with Diphtheria Toxin vaccine.

Bordetella pertussis pathogen

extremely small, Gram negative cocco-bacilli.

Bordetella pertussis encounter

human are the only known natural reservoir.

Bordetella pertussis entry

inhalation of contaminated respiratory droplets.

Bordetella pertussis spread and multiplication

extracellular growth, spread quickly from nasopharynx to trachea, bronchi, and bronchioles. bacteria produces a thick polysaccharide and kills ciliated epithelial cells contributing to its spread.

Bordetella pertussis damage

mediated by multiple powerful exotoxins and host immune response.

Bordetella pertussis diagnosis

characteristic whooping cough. nasopharyngeal swab onto Bordet-Gengou media or Regan-Lowe media followed by gram stain and sero-testing.

Bordetella pertussis treatment and prevention

erythromycin or trimethoprim-sulfamethoxazole. Intrinsically resistant to penicillin. Prevent through vaccination.

Bordetella pertussis Pertussis Toxin

free and found on bacteria surface. AB Toxin, inhibits recruitment of immune cells to infection site, toxin in the blood stream may lead to leukocytosis

Bordetella pertussis Adenylate Cyclase Toxins

Found on cell surface, interacts with cell surface complement receptors on macrophages and neutrophils, inhibits antigen presentation, proinflammatory cytokine release, complement mediated phagocytosis, and immune cell recruitment.

Bordetella pertussis Filamentous hemaglutinin

protein filament on bacteria surface facilitates attachment of bacteria to epithelium

Bordetella pertussis tracheal cytotoxin

fragment of peptidoglycan that binds ciliated epithelial cells

Bordetella pertussis pathogenesis

bacteria attaches to ciliated epithelium using filamentous hemaglutinin and cell bound pertussis toxin. release tracheal cytotoxin, cilia movement is inhibited. bacteria numbers rise, high TCF, kills ciliated cells and they slough off into mucous. thicker mucous, spread of bacteria.

Bordetella pertussis catarrhal stage

after 7-10 day incubation period, common cold stage. runny nose, sneezing, malaise, anorexia, low grade fever. highest number of bacteria are made during this phase, no recognition by characteristic whooping cough.

Bordetella pertussis paroxysmal stage

whooping cough, repetitive cough followed by whoop. typically end with vomiting and exhaustion. 40-50 cough a day, aspiration can occur.

Bordetella pertussis convalescent stage

paroxysms decrease in number and severity. secondary complications can be seen including pneumonia and otitis media. 100 day cough

Escherichia coli pathogen

gram negative rod, 0.9 width, 1-3 um long

Escherichia coli encounter

human and animal normal flora, found in soil and water

Escherichia coli entry and spread

ingestion, wound infection, or endogenous spreading. EPEC human human spread

Escherichia coli multiplication

extracellular growth in multiple tissues, intestine, urogenital tract, blood, meninges, etc. EIEC and UPEC can replicate intercellularly.

Escherichia coli damage

gastroenteritis and UTI most common. generally caused by toxin release at site of infection and the immune response. most toxins are plasmid borne

Escherichia coli diagnosis

growth on selective media. physiological tests, serotyping and nucleic acid testing.

Escherichia coli treatment and prevention

treatment depends disease state and in vitro antimicrobial susceptibility testing (amoxicillin, ciprofloxacin, kanamycin, are often successful). gastroenteritis is often treated with just rehydration therapy. prevention includes proper hygeine, properly cooking beef.

ETEC

Traveler’s diarrhea, infant diarrhea in developing countries, watery diarrhea, vomiting, cramps, nausea, low-grade fever. no person to person spread, after 1-2 days incubation, watery diarrhea which persists for 3-5 days. self limiting, rehydration therapy, antibiotics used only for the elderly, pregnant women, immuno-suppressed, and young children.

ETEC pathogenisity

ETEC attaches to macrovilli via colonizing factor adhesion, releases two enterotoxins. Heat Labile Toxin, LT-I is an AB toxin. B subunit facilitates entry via endocytosis, A subunit inhibits Na transport. Heat Stable Toxin, STa, binds host Guanylyl cyclase which stims production of cGMP. water and Na diffuse out of the cell and is responsible for fluid loss and diarrhea.

EPEC

Infant diarrhea in underdeveloped countries, watery diarrhea and vomiting, non-bloody stools. person to person spread, low ID

EPEC pathogenisis

bundle forming pilus, BFP, initiates contact with host cell microvilli (inhibs phagocytosis) Type 3 secretion system secretes Tir and EspF into cell. Tir binds bacterial protein intimin leading to pedestal formation. EspF disrupts tight junctions between cells leading to fluid loss, also induces cell apoptosis.

EHEC

initial watery diarrhea, followed by grossly bloody diarrhea and abdominal cramps, little or no fever. may disseminate and progress to hemolytic uremic syndrome (HUS). As few as 100 bacteria needed to cause disease.

EHEC pathogenesis

EHEC releases Shiga Toxins (StxA, StxB). These are AB toxins that bind host cell receptors on intestinal epithelial cells. endocytosis, leads to B subunit and delivery of A subunit. A subunit causes cell death. Siga Toxin enters blood stream, travels to kidneys, platelet activation and lysis of red blood cells cause blood clots, renal failure and death.

EHEC treatment

initially fluoroquinolones, but led to widespread antibiotic resistance. contraindicates antibiotic treatment in most cases. patients with HUS are placed of hydration therapy, antiplatelet agents and often hemodialysis

UPEC

Responsible for 90% of Urinary Tract Infections in people with normal anatomy. Can ascend to infect bladder, kidneys, or prostate (male patients). Associated with dysuria, frequent and persistent urge to urinate, and sometimes abdominal pain, fever, fatigue and malaise.

UPEC Pathogenesis

FimH binds uroplakin receptors on superficial bladder cells. initiates cytoskeletal rearrangements and invades superficial bladder cells. activates immune system. activates phagosome/endosome and grows in cytoplasm. UPEC transitions to growth in intracellular bacterial communities and to filamentatous growth. Apoptosis and exfoliation of bladder cells. UPEC escapes dying superficial bladder cells and infects underlying epithelial cells. can come back and persist.

UPEC Diagnostics and Treatment

UPEC infections are diagnosed from clean catch urine specimens and plated on both Blood Agar and MacConkey Agar. Beta-hemolytic on blood agar and present with characteristic mucoid colonies. Lactose fermentation positive. amoxicillin, ciprofloxacin, or kanamycin.

salmonella enterica pathogen

gram negative rod, 0.7-1.5 by 2-5 um

salmonella enterica encounter

animal normal flora, found in soil and water. human asymptomatic carriers.

salmonella enterica entry and spread

ingestion of contaminated food or water.

salmonella enterica multiplication

intracellular growth in intestinal epithelial cells, M cells, and leukocytes.

salmonella enterica damage

acute gastroenteritis from infection, enteric/typhoid fever can develop if bacteria invade bloodstream

salmonella enterica diagnosis

culture on selective media, physiological tests, serotyping.

salmonella enterica treatment and prevention

depends on disease state and in vitro antimicrobial susceptibility testing (ciprofloxacin and ampicillin, are often successful). gastroenteritis is often treated with just rehydration therapy. septicemia and typhoid are treated with antibiotics. prevention include proper preparation and cooking of poultry and eggs and proper hygiene. Vaccine is available 50-80% efficacy and generally recommended for travelers.

salmonella enterica physiology

gram negative, facultative anaerobic rods, motile, ferments glucose, does not ferment sucrose or lactose. oxidase negative, reduces sulfur, resistant to bile salts, effected by freezing.

salmonella enterica pathogenesis

M-cells transcytose from small intestine lumen to lymphatic tissue. SPI-1 encodes Type 3 secretion system and bacterial effector proteins that facilitate invasion of the bacteria into intestinal epithelial cells.

salmonella enterica Typhi pathogenesis

can disseminate to mesenteric lymph nodes via infected phagocytes. enter lymph and bloodstream and spread. liver and gall bladder infection can act to reseen the lumen of intestine in cases of typhoid fever.

salmonella enterica typhi (enteric fever)

caused only by typhi serovar, 10-14 days after infection, patients experience gradually increasing fever, headache, myalgias, malaise, and anorexia. colonization of liver, spleen, bone marrow lead to bacteremia and colonization of gall bladder.

Typhoid fever diagnosis

<1 week after onset of fever, the organism can be cultured from the blood samples but less frequently in fecal materials. 2-3 weeks - organism is culturable from fecal material and sometimes isolated from urine samples. Beyond four weeks, very hard to culture.

salmonella enterica prevention

heat phenol inactivated vaccine (children above 2), oral live attenuated bacteria (children above 7), polysaccharide vaccine

Shigella sp.

causative agent for bacterial dysentery, bacillus, ferments glucose, does not ferment mannitol, non motile, no capsule, oxidase negative, no endospores, h2s negative.

shigellosis

initial watery diarrhea, progresses in 1-2 days to abdominal cramps, fever, and tenesmus (feeling of needing to pass stool when bowels are empty). caused by S. sonnei, S. boydii, and S. flexneri. usually self limiting, 5-7 days without treatment.

bacterial dysentery

severe form of shigellosis, high fever blood and pus containing stools, tenesmus, rectal prolapse. can progress to HUS. caused by S. dysenteriae. Severity associated with Shiga toxin, treated with antibiotics.

Shigella pathogen

gram negative rod

shigella encounter

human reservoir, persists in water

shigella entry and spread

fecal-oral transmission, spread person to person or via ingestion of contaminated food and water

shigella multiplication

intracellular growth in intestinal epithelial cells, primarily in colon

shigella damage

shigellosis is a gastroenteritis in most cases, S. dysenteriae can cause dysentery. dysentery cases can progress to HUS due to shiga toxin.

shigella diagnosis

CIDT followed by growth on selective media, Shigella die very quickly after excretion so prompt culturing is needed

shigella treatment and prevention

treatment depends on disease state and in vitro antimicrobial susceptibility testing. gastroenteritis is generally self limiting and treated with supportive care. severe cases of gastroenteritis and dysentery are treated with antibiotic (Bactrim). prevention includes proper hygiene, sanitation, and infection control.

shigella pathogenesis

taken up by M-cells and translocates across M cells (needs type 3 secretion system). engulfed by macrophages, macrophages secrete IL-1 and IL-8 to recruit macrophages and lymphocytes, illicit an immune response. tight junctions in intestine loosen, induces apoptosis of macrophages. effector proteins are secreted and bacteria is taken up into intestinal epithelial cells.

Shigalla pathogenic multiplication

once engulfed by epithelial cells, bacteria secretes IpaB and IpaC into lumen of phagosome. Bacteria escape, shigella multiplies in the cytosol

Shigella toxins

Shigella enterotoxin 1 (ShET-1): chromosomal encoded toxin. cytotoxic, in certain strains.

Shigella enterotoxin 2 (ShET-2): virulence plasmid encoded AB toxin. similar to ETEC heat labile toxin

Shiga toxin A and B (StxB, StxA): identical to shiga toxin in EHEC. only in S. dysenteriae.

clostridium spp.

gram positive bacilli obligate anaerobes, all form endospores, drumstick shaped, ubiquitous in soil, water, sewage, able to form endospores, rapid growth in nutrient rich, oxygen deprived environments, release multiple potent toxins during multiplication

Clostridium perfringes pathogen

gram positive rod

Clostridium perfringes encounter

ubiquitous organism found in soil and water. normal intestinal flora in animals.

Clostridium perfringes entry and spread

wound infection by spores

Clostridium perfringes multiplication

extracellular anaerobic growth in either soft tissue or intestinal tract

Clostridium perfringes damage

cellulitis, supparative myositis, myonecrosis

Clostridium perfringes diagnosis

gram stain tissue samples. grows rapidly on blood agar in anaerobic conditions. naglar reaction, litmus milk test.

Clostridium perfringes treatment and prevention

gas gangrene is treated with wound debridement and high dose penicillin therapy, maybe hyperbaric oxygen chamber. gastroenteritis is usually self limiting.

Clostridium perfringes type A

inhabits intestinal tract of humans and animals and is regularly found in soil and water contaminated with feces

Clostridium perfringes type c

necrotizing enteritis in humans

Clostridium perfringes a toxin

phospholipase c, membrane damage toxin (A), hydrolytic enzyme (B) act on both extracellular substrates and substrates from cell lysis

Clostridium perfringes pathogenesis

penetrating wound introduces spores into an anaerobic environment, spores germinate, vegetative cells express toxins causing local cell dead and provide nutrients for growth. growth of the organism leads to gas production from anaerobic respiration. gas produced, bacterial growth and the immune response, results in more tissue damage allowing the organism to spread.

clostridium tetani encounter

contaminated soil, can colonize human and animal intestinal tract

clostridium tetani entry

spore contamination of wound or puncture wound with spore contaminated object

clostridium tetani spread

spores are ubiquitous in soil, point object spread

clostridium tetani multiplication

spores germinate. anaerobic, extracellular growth

clostridium tetani damage

three different forms: generalized tetanus, localized tetanus, neonatal tetanus. damage is the result of tetanospasmin, a potent neurotoxin. can be fatal in four days without treatment.

clostridium tetani diagnosis

clinical presentation. microscopic detection is possible, but difficult. only 30% success with culture of patient sampling (branching colonies on blood agar). organism is very sensitive to oxygen

clostridium tetani treatment

debridement of infected wound, treatment with penicillin or metronidazole. passive immunization and vaccination with tetanus toxoid vaccine.

clostridium tetani prevention

tetanus is rare in developing countries due to a very effective vaccine

clostridium tetani pathogenesis

enters body through wound, stays in spore form until anaerobic conditions are presented, germinates, multiplies, and produces tetanospasmin, toxin spreads in blood and lymph. system, binds to motor neurons, travels along axons to spinal cord, binds to sites responsible for inhibiting skeletal muscle contraction.

clostridium tetani tetanus toxin activity

B (heavy chain) binds to neuronal membrane, contains domain which aids movement of A (light chain) across vesicle membrane into cell. A cleaves VAMPs proteins that regulate release of inhibitory neurotransmitters.

clostridium tetani clinical manifestations

General:

lock jaw, ricus sardonis (joker smile), persistent back spasms and prolonged muscle action, can lead to fractures and tears, drooling, sweating, irritability

Local:

uncommon, remains confined to muscle closest to primary infection

Neonatal;

Developing countries where mud is wrapped around umbilical cord.

Clostridium difficile encounter

contaminated food, water, soil, normal flora in 5% of healthy individuals. most patients exposed in hospital setting

Clostridium difficile entry

ingestion of normal flora. exposure to antibiotics can facilitate colonization, naturally resistant to many antibiotics, colonizes vacant niche.

Clostridium difficile spread

organism spread to unoccupied sites in instestinal tract via overgrowth

Clostridium difficile multiplication

anaerobic, extracellular growth in colon

Clostridium difficile damage

Gastroenteritis, with watery diarrhea, fever, lower abdominal cramping. Colitis and/or Pseudomembrane colitis are possible. Mediated by TcdA & TcdB which cause depolymerization actin cytoskeleton of intestinal epithelial cells causing cell death. TcdA also stimulates inflammatory response and is a chemoattractant for neutrophil

Clostridium difficile diagnosis

detection of toxin by immunoassay or a NA test. stool culture on CCFA agar