Gram negative rods -- 2018 update

Categories of gram negative rods: Site of infection

Enteric tract
Respiratory tract
Acquired from animals (zoonoses)

Enteric tract

Within and outside the enteric tract: Escherichia, Salmonella
Primarily within: Shigella, Vibrio, Campylobacter, Helicobacter
Outside only: Klebsiella-Enterbacter-Serratia group, Proteus-Providencia-Morganella group, Pseudomonas, Bacteroides

Respiratory tract

Haemophilus
Legionella
Bordetella

Acquired from animals (zoonoses)

Brucella
Francisella
Pasteurella
Yersinia

Categories of gram negative rods: Enterobacteriaceae

Family of gram-negative rods found primarily in the colon--often normal flora
Facultative anaerobes---can survive in aerobic conditions for a period of time, but mostly anaerobes
Within and outside the enteric tract: Escherichia, Salmonella
Primarily with

Enterobacteriaceae Gram staining

Gram negative

Enterobacteriaceae Shape

Rods

Enterobacteriaceae Aerobic/Anaerboic

Facultative Anaerobes

Enterobacteriacae: Pathogenesis

Endotoxin (all are gram negative)
Several exotoxins: Specific for individual species

Escherichia coli

Most abundant facultative anaerobe in colon and feces
3 antigens used for identification:
O = cell wall
H = flagella
K = capsule
Yields over 1000 antigenic types of E. coli
Slide 5 Gram negative rods

Diseases associated with Escherichia coli

Urinary tract, bladder & kidney infections---most common cause of this type of infection
Septicemia
Pneumonia
Meningitis
Diarrhea
Dysentery
Hemolytic uremic syndrome

E. Coli Pathogenesis---UTIs

Urinary tract infections (80 to 90% of all cases)
Risk of spread to bloodstream (sepsis)
Slide 7 Gram Negative Rods

E. Coli: Pathogenesis---UTIs: Why are men usually spared?

Location, location, location
Location of the male urethra is much farther away & shielded by anatomy than females
Slide 8 Gram Negative Rods

Urinary tract infection due to Escherichia coli

E coli on outside of body, short urethra & some E.coli gets into urethra
E. coli are motile, because have flagella
Can swim their way up into the bladder
If void, can eliminate the bacteria----recommended to urinate after sexual activity
If do not void or

Sepsis and Septic Shock

Bactermia: Presence of viable bacteria in bloodstream
Systemic inflammatory response syndrome (SIRS): Systemic inflammatory response to a variety of clinical insults which can be an infection, but can also be noninfectious. Manifested by 2 or more of the

Sepsis is an infection, leads to

inflammatory response to bacterial blood infection

Order of Sepsis to Septic shock

Bacteremia
Sepsis
Severe sepsis
Septic shock
Refractory septic shock
Multiorgan dysfunction syndrome

Bacteremia

Presence of viable bacteria in bloodstream

Systemic inflammatory response syndrome (SIRS)

Systemic inflammatory response to a variety of clinical insults which can be infection, but can also be non-infectious.
Manifested by 2 or more of the following:
Tachycardia
Tachypenea
Hyperthermia or hypothermia
Extremely high or low WBC count

Sepsis

Systemic inflammatory response syndrome (SIRS) secondary to infection

Severe sepsis

Sepsis plus evidence of altered organ perfusion
Reduction in urine output
Mental status changes
Hypoxemia
Systemic acidosis

Septic shock

Sepsis syndrome with development of severe hypotension (shock)

Refractory septic shock

The hypotension of septic shock is not responsive to pharmacologic treatment

Multiorgan dysfunction syndrome

Failure of kidneys, lungs, liver, (highly perfused organs) and DIC = disseminated intravascular coagulation

Dissmeniated intravascular coagulation Pathoglogy

Clots in the skin & internal tissues
Body has responded to bacteria by throwing clots & trying to stop infection from spreading
Extravasation of fluids, because of hypotension, damage to endothelial cells & then clotting
Body is trying to wall off the inf

Mechanisms responsible for development of shock

Bacterial endotoxin (lipopolysaccharide, macromolecules that come from bacteria (not endogenous), body recognizes as foreign) causes the release of cytokines and activation of the coagulation system
Biologic effects of these endotoxin-induced actions:
Fev

Endotoxin (only gram negative bacteria)

Lipopolysaccharide (LPS) is located within the outer membrane of Gram negative bacteria
Lipid A is responsible for toxic effect
Lipid A is recognized by toll-like receptors----leads to release of cytokines
Slide 13 Gram Negative Rods

Why filter IV fluids instead of autoclaving?

The endotoxin is not heat-labile----bacteria is killed, but the endotoxin will remain & will elicit the cytokine release

Other activators of septic shock

Lipooligosaccharides (N. gonorrhea)
Lipoproproteins (spirochetes)
Gram positive cell wall components: teichoic acid and peptidoglycan

E. coli pathogenesis: 4 Intestinal Diseases

Enterotoxigenic E. coli (ETEC)
Enteropathogenic E. coli (EPEC)
Enterohemmorhagic E. coli (EHEC)
Enteroinvasive E. coli (EIEC)

Enterotoxigenic E. coli (ETEC)

Traveler's diarrhea and infant diarrhea (important in developing countries)
Fecal-oral
Enterotoxin = Heat labile toxin (LT)
Hypersecretion of ions and water = water diarrhea
Small intestine
Increases cAMP = increases amount of water, electrolytes & blood

Enteropathogenic E. coli (EPEC)

Infant diarrhea---infected at birth
EPEC attach to small intestinal mucosal cells and destroy microvilli
Watery diarrhea

Enterohemorrhagic E. coli (EHEC)

Hemorrhagic colitis
EHEC (ex: O157:H7) binds to large intestine cells
Produce verotoxin---kills intestinal cells
Copious bloody diarrhea (dysentery) without mucosal invasion or inflammation

Enteroinvasive E. coli (EIEC)

Similar to shilgella
Invade large intestine epithelial cells
Bloody diarrhea (dysentery) with inflammatory (neutrophil) cells in stool

E. coli pathogens that affect small intestine

Enterotoxigenic E. coli (ETEC)
Enteropathogenic E. coli (EPEC)

E. coli pathogens that affect large intestine

Enterohemorrhagic E. coli (EHEC)
Enteroinvasive E. coli (EIEC)

ETEC: Labile toxin (LT) action

Cholera toxin functions similarly
Labile to heat
Bacteria binds to the receptors on the intestinal cell & get into the cell
Then it ADP-ribosylates a protein that stimulates adenylate cyclase
This results in activation of adenylate cyclase & increases lev

E. coli O157:H7 Infections: Zoonotic origins

Enterohemorrhagic E. coli: EHEC
Found in more developed countries, where have animals being farmed in very close quarters
Slide 19 Gram Negative rods

EHEC: E. coli O157:H7 Infections

Organism kills off some of the cells in the intestine through the action of the verotoxin
Damages the intestine itself, but the verotoxin can also get into the blood and damage the epithelial cells, which can lead to bleeding & coagulation----end up with

What 2 complications are most worrisome from E. coli O157:H7 infections?

Hemorrhagic colitis
Hemolytic uremic syndrome

Salmonella species

Facultative, intracellular parasite
Survives in phagocytic cells
Initially invades epithelial cells of the small intestine
Symptoms due to endotoxin
Slide 21 Gram negative rods

Salmonella enterica

1500 serotypes
Source: Humans, animals, and food
Major cause of food poisoning from poultry, eggs, and pork
Causes gastroenteritis:
Localized disease: Penetration of mucosal cells by bacteria
Nausea, diarrhea, vomiting

Salmonella typhi

1 serotype
Typhoid fever (enteric fever)----starts in intestine, then spreads to the Peyer's patches
Then the bacteria's endotoxin gets spread systemically by phagocytes
This leads to bacteremia and fever
Mortality rate is 15% if not treated---due to burs

Categories of Gram Negative Rods: Site of Infection: Primarily within

Shigella, Vibrio, Campylobacter, Helicaobacter

Shigella

Intracellular
Low ID50 (under 100)---takes very few organisms to cause infection
Fecal-oral transmission from humans only
Causes Shigellosis
Bloody diarrhea with mucous
Painful abdominal cramping
Very similar to EIEC

Shigella: Pathogenesis associated with cellular invasion

Intracellular infection of enteric cells, which can lead to the damage to the cells/death of the cells----leads to bloody diarrhea
Inflammatory response as well
Slide 26 Gram Negative Rods

Vibrio

Vibrio cholerae causes cholera
Fecal-oral transmission
Usually from contaminated water
Vibrio parahaemolyticus
Marine organism
Causes diarrhea after eating raw shellfish
Slide 27 Gram Negative Rods

Vibrio cholerae: Pathogenesis

Causes watery diarrhea in large volumes (rice-water stool)
No abdominal pain
Massive fluid and electrolyte loss
Cardiac and renal failure
Mortality w/o treatment = 40%
ID50 = 10^6

Mechanism of Vibrio cholerae

Cholera toxin causes active secretion of ions and water in the small intestine by activating adenylate cyclase and increases cAMP
Need to replace water and electrolytes to treat this

Helicobacter pylori

Primary cause of gastric and duodenal ulcers, gastritis
Patients with Heliobacter infections have higher risk of stomach cancer
Produces urease (NH3 generation)---ammonium ion generation
Slide 30 Gram Negative Rods

Heliobacter pylori: Pathogenesis

Organism does not want to live in the really low pH of stomach acid, so it is creating an environment for itself (by generating ammonium ions) to insulate itself from stomach acid
If develop an ulcer, mucus layer starts to go away & start damaging the tis

Campylobacter jejuni

S-shaped rod
Microaerophilic
Domestic animals are reservoir
Transmitted by fecal-oral in food (poultry, unpasteurized milk)
**Most common cause of gastroenteritis
Produces enterocolitis
Foul-smelling water diarrhea
Bloody stools and severe abdominal pain

Categories of gram negative rods: Site of infection: Outside only

Klebsiella-Enterobacter-Serratia, Proteus-Providencia-Morganella group, Pseudomonas, Bacteroides

Klebsiella, Enterobacter, Serratia

- Klebsiella pneumonia
- Enterobacter
- Serratia marsescens
Common traits:
Found in large intestine, soil and water
Opportunistic nosocomial (hospital) pathogens
Pathogenesis = UTIs and pneumonias
Klebsiella pneumnoiae = hospital acquired pneumonia
Predis

Proteus, Providencia, Morganella

Proteus vulgaris and Proteus mirabilis---produces ureases
Providencia rettgeri
Morganella morgnii
Common traits:
Present in the colon (and soil and water) therefore UTI = primary pathogenesis----do not cause disease in colon, just urinary tract
All are ur

Pseudomonas aeruginosa

Different from all other Enterobacteriaceae
Strict aerobe----needs air to survive
Oxidase positive
Actively motile
Cultures:
blue-green pigment
fruity odor
Does not usually cause infection, but if there is a break in the skin---has a great ability to grow

Pseudomonas aeruginosa Gram staining

Gram negative

Pseudomonas aeruginosa Shape

Rods

Pseudomonas aeruginosa Aerobic/Anaerobic

Aerobic only

Bacteroides fragilis

Not very fragile
Anaerobic (Facultative anaerobic)
Non-spore forming
Rods
[Predominant organism in the colon: only apply to Bacteroides in general]
10^11 cells/g feces
E. coli = 10^7 to 10^8 cells/g feces
Endogenous infections:
- Intra-abdominal infection

Zoonoses

- Brucella
- Francisella tylarensis (pop: trappers, trapping animals)
Need to know:
- Pasteurella multocida
- Bartonella henselae
- Yersinia pestis

Pasteurella multocida

- Wound infections from dog and cat bites
-

Bartonella henselae

Cat Scratch Fever
- Facultative, intracellular gram neg rod
- Cat Scratches and bites
- Pathogenesis is mild and self-limiting

Yersinia pestis

- Highly infectious (ID50 = 1-10)
- Pathogenesis (mostly endotoxin related)
- Bubonic plague (Black death, shock & sepsis)
- Pneumonic plague (Bacterial growth in lung, blood in sputum, meningitis)
- Reservoir: rats, squirrels