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→Pathogenesis
{{review}}
===''Eschericia coli'' (''E. coli'') overview===
* Enterotoxigenic ''E.coli'' contributes to [[Intestines - Catarrhal Enteritis#Undifferentiated Neonatal Calf Diarrhoea|undifferentiated neonatal calf diarrhoea]], a mixed viral enteritis in calves.
[[File:Ecoli.jpg|200px|right]]
* [[Intestines - Catarrhal Enteritis#Colibacillosis|Colibacillosis]].
*Member of ''Enterobacteriacae'' family of Gram-negative bacilli
* [[Intestines - Inflammatory Bowel Disease And Related Conditions#Histiocytic Ulcerative Colitis|Histiocytic ulcerative colitis]] in the dog and cat.
*'''Facultative anaerobe'''
* Causes [[Intestines - diarrhoea#Secretory Diarrhoeas|secretory diarrhoea]]
*One of predominant bacterial species in colonic flora
* Causes [[Peritoneal cavity - inflammatory#In dogs|peritonitis in dogs]] and [[Peritoneal cavity - inflammatory#In pigs|peritonitis in pigs]]
*Colonisation of intestinal tract from environmental sources shortly after birth
*Abundant in the environment
*Most strains have low virulence
*Found in many non-specific, endogenous infections, eg. wound infections, upper respiratory tract infections, infections of the urinary tract, mammary glands and uterus and septicaemia
*An enteropathogen, causing neonatal diarrhoea in young animals and enteric colibacillosis
*Enterotoxigenic ''E. coli'' is the most common cause of diarrhoea in calves, lambs and pigs
*Pathogenic strains possess virulence factors allowing colonisation of mucosal surfaces
===''E. coli'' characteristics===
*Usually motile with flagella and fimbriae
*'''Oxidase negative''' (do not possess cytochrome C oxidase)
*Grow on '''MacConkey agar''' (in presence of bile salts), producing pink colonies
*'''Haemolytic activity'' on blood agar characteristic of certain strains
*'''Lactose fermenter'''
*Reduce nitrates to nitrites and ferment glucose to produce acid and gas
*Possess a lipopolysaccharide ('''O''') antigen, a flagellate ('''H''') antigen, polysaccharide capsule ('''K''') antigens and fimbrial ('''F''') antigens
*Epidemiological typing of ''E. coli'' uses antigen combinations, eg. O125:K12:H42
===Pathogenesis===
*<u>Virulence factors</u> include capsules, endotoxin, enterotoxins and colonisation factors
*Capsular polysaccharides produced by some strains prevent phagocytosis and interfere with complement
*Endotoxin is a lipolysaccharide component of the cell wall of Gram-negative bacteria, composed of lipid A, a core polysaccharide and various side chains
*'''Endotoxin''' is realeased when bacteria die, and causes endothelial damage leading to [[Disseminated Intravascular Coagulation|'''disseminated intravascular coagulation''']] and '''endotoxic shock'''; it is also a '''pyrogen'''
*Enterotoxins, verotoxins and cytotoxic necrotising factors produced by many pathogenic ''E. coli''; these produce cell damage at their site of action
*'''Alpha-haemolysin''' may increase iron availability for invading organisms
*'''Siderophores''' are made by certain pathogenic strains, and are responsible for iron aquisition; they include aerobactin and enterobactin
==Extra-intestinal infection==
*Soft tissue infections in adult animals
*Pathogenesis:
**Produces an alpha-haemolysin which may be cytotoxic
**Iron aquisition system
**K antigens prevent phagocytosis or mimic host antigens and resist complement
**Fimbriae permit adhesion to mucosal surfaces
**May enter blood to cause septicaemia
*Clinical infections:
**'''Urogenital tract infections'''
***Most common organism infecting urinary tract
***Ascending infections of urinary tract
***Causes pyometra in the dog and cat and [[Pyelonephritis|pyelonephritis]]
***Cystitis in the bitch
***Prostatitis in dogs via opportunistic infection
***Colonisation of mucosa aided by fimbriae
**'''Mastitis'''
***Opportunistic infection of mammary glands of sows and cows
***Endotoxaemia in the acute form often fatal
***Death within 24-48 hours during peracute disease
***Animals depressed with sunken eyes
**[[Colibacillosis|'''Colibacillosis''']]:
***Avian:
****Septicaemia in newly-hatched chickens
****Infection enters via faecal contamination of the egg surface or via the ovary of the hen
****Infection enters via the respiratory tract
****A bacteraemia develops
****Acute colisepticaemia, subacute fibrinopurulent serositis or chronic granulomatous disease of the viscera
****Occurs in older birds via inhalation of ''E. coli'' in dust; respiratory infection spreads to the blood to cause acute colisepticaemia
****Airsacculitis, pericarditis and perihepatitis during acute phase
****Often secondary to virus or [[:Category:Mycoplasmas|''mycoplasma'']] infection or environmental stress
**'''Colisepticaemia''':
***Systemic disease in young calves, piglets, foals, lambs
***Penetration of intestinal mucosa and entrance into the blood
***Invasive strains survive the host defences
***Virulence related to adhesive properties, complement resistance and ability for iron aquisition
***Ammonia, dust, viral infections and temperature changes enhance likelihood of disease
**[[Oedema Disease|'''Oedema disease of pigs''']]:
**'''Watery mouth of lambs''':
***Affects lambs under three days old
***Lack of colostrum allows collonisation and overgrowth of ''E. coli'' in the small intestine
***Systemic invasion by ''E. coli''
***Absorption of endotoxin leads to death
***Severe depression, anorexia, salivation and abdominal distension
***Morbidity and mortality high
** [[Inflammatory Bowel Disease#Histiocytic Ulcerative Colitis|Histiocytic ulcerative colitis]] in the dog and cat.
** Causes [[Peritonitis - Cats and Dogs|peritonitis in dogs]] and [[Peritonitis#In pigs|peritonitis in pigs]]
**Found in [[Osteomyelitis|osteomyelitis]]
**Associated with neonatal [[Infectious Arthritis#In Cattle|polyarthritis of calves]]
**In [[Deep Pyoderma|deep pyoderma]]
**Found in [[Infectious Arthritis#In Horses|arthritis of horses]]
==Intestinal infection==
*''E. coli'' is part of the flora of the large intestine, but is not usually found in the small intestine
*Some strains possess fimbrae which attach the bacteria to the small intestinal epithelium of particular animal species
*''E. coli'' may cause diarrhoea via attaching and effacing lesions, where bacteria adhere intimately to the enterocyte, and cause localised effacement of the brush border microvilli; the epithelial erosion causes [[Haemorrhage#Dysentery|dysentery]]
*'''Enterotoxigenic ''E. coli'' (ETEC)''':
**General:
*** Contributes to [[Calf Diarrhoea, Undifferentiated Neonatal|undifferentiated neonatal calf diarrhoea]], a mixed viral enteritis in calves, also known as enteric colibacillosis
***Causes scours in pigs, calves and lambs
***'Traveller's diarrhoea' in humans
**Pathogenesis:
***Oral infection, intestinal colonisation and toxin production
***Fimbrial antigen or colonisation factor antigens (CFAs)determine species specificity
***Fimbrial adhesins allow bacteria to attach to mucosal surfacesin the small intestine and lower urinary tract; this prevents expulsion by peristalsis and flushing of urine
***K88 (F4) is associated with adhesion to the small intestinal mucosa of pigs
***K99 (F5) associated with adhesion in pigs and cattle (these fimbrial adhesins were originally thought to be capsular (K) antigens)
***The '''fimbriae are encoded by plasmids'''
***These strains carry a plasmid which encodes an enterotoxin
***Two types of '''enterotoxin: heat-labile (LT) and heat-stable (ST) toxins'''
***The '''plasmids''' which produce these toxins are '''responsible for the pathogenicity''' of these strains
****'''LT'''
*****An oligometric toxin composed of an enzymatically-active A subunit (30KDa; 2 fragments - A1 and A2) and 5 identical B subunits (12KDa) forming the binding portion (B oligomer)
*****It attaches to the brush border of the epithelial cells of the small intestine
*****Causes ADP-ribosylation of the stimulatory subunit of guanine nucleotide binding proteins of the adenylate cyclase complex in eukaryotic cell membranes
*****This causes irreversible activation of adenylate cyclase in target cells
*****This raises the cAMP level and causes hypersecretion of water and chloride ions into the lumen of the small intestine and inhibits reabsorption of sodium
****'''ST'''
*****Activates guanylate cyclase in enteric epithelial cells, stimulating fluid secretion
**Clinical signs:
***The gut becomes distended with fluid and a [[Diarrhoea#Secretory Diarrhoeas|secretory diarrhoea]] which lasts several days results
***Watery diarrhoea, dehydration, acidosis, death
**Immunity:
***LT is antigenic
***Immunity is developed via production of antibody to LT protein and fimbrial antigen
***Parenteral vaccination of pigs and cattle protects offspring from scours via antibody production in the colostrum (passive immunity)
***ST is not immunogenic; it is small, with only 19 amino acids
*'''Enteropathogenic ''E. coli'' (EPEC)''':
**Attaching and effacing strains of ''E. coli''
**Attach to small intestinal epithelial cells and cause necrosis of enterocytes and stunting and fusion of villi
**Possess ''E. coli'' adherence factor plasmid
**An adhesin, intimin is required for attachment to enterocytes
**Secrete signalling proteins that activate a tyrosine kinase, causing rearrangement of cytoskeletal proteins and effacement of microvilli
**Intracellular calcium levels increase and production of protein kinase C causes loss of chloride ions and water from the intestinal epithelial cells
**Diarrhoea results
*'''Enteroinvasive ''E. coli''''':
**Cause colisepticaemia in calves during their first week of life; occasionally in lambs, piglets and puppies
**Infection via ingestion or umbilicus; inadequate colostrum increases susceptibility
**Invade epithelial cells of small intestine by inducing endocytosis
**Traverse gut wall to lamina propria and enter lymphatics
**Resistant to complement-mediated killing
**Bacteraemia or septicaemia and endotoxaemia
**Widespread petechial haemorrhages of organs and serosa
**Abscesses, pneumonia in long term
**Death occurs in absense of treatment
*'''Enterohaemorrhagic ''E. coli''''':
**Possibly carried by cattle
**Produce shiga-like toxin, a vero toxin
**Plasmid-coded fimbriae important for virulence
**Intimin produced allowing intimate attachment to intestinal epithelial cells
**Strains do not product LT or ST and are not enteroinvasive
**Attaching and effacing lesions, unrelated to toxin production
**[[Disseminated Intravascular Coagulation|Disseminated intravascular coagulation]] and thrombus formation
**''E. coli'' O157:H7 causes haemorrhagic collitis-haemolytic uraemic syndrome in humans
*'''Cytotoxin necrotising factor-producing ''E. coli'''''
**Infrequently cause diarrhoea in calves, pigs and humans
**Important virulence factors include toxin and fimbriae
==in cattle==
*Neonatal polyarthritis:
**[[Escherichia coli|'''''Coliforms''''']]
***Localises in joints and meninges in severe non-fatal neonatal colibacillosis
***May remain as chronic arthritis in larger joints
[[Category:Enterobacteriaceae]]
[[Category:To_Do_-_Bacteria]]