E.coli Flashcards
Escherichia Coli
Gram-negative rods (red stain)
Typically lactose-fermenting
Facultatively anaerobic - can survive with O2 present - but rather anaerobic conditions
Often motile
Numerous serotypes - Constituent part of large bowel microbiota of many animals, including humans
The
Identifying E.coli in the lab
E coli and other Enterobacteriaceae can use the sugar lactose as an energy source, producing lactic acid as a waste product.
Pseudomonas aeruginosa cannot use lactose –it is a non-lactose fermenter
MacConkey agar contains lactose and a pH indicator that goes red with acid pH
E coli and other Enterobacteriaceae grow as pink colonies on MacConkey agar. Non- lactose fermenters grow as yellow colonies
The diversity of E.coli
E coli have been typed using a number of methodologies over the years, reflecting the development of new typing technologies
Serology –using antibodies to detect different bacterial surface antigens – O, H, K, F antigens
Metabolic profiling –variation in biochemical pathways
Genomic diversity - using DNA hybridisation. multi-locus enzyme electrophoresis (MLEE), multi-locus sequence typing (MLST) whole genome sequencing
E.coli in health and disease
E coli is a normal component of large bowel microbiota in humans and many other animals
Possibly protects against invasion by pathogenic species such as Salmonella BUT:
E coli can also cause: intestinal infections (diarrhoea) toxin-mediated disease extra-intestinal infections - i.e. E.coli getting into the wrong place e.g. Urinary tract Intra-abdominal Biliary tract Bloodstream infection Neonatal meningitis
The propensity to cause disease is linked to the presence of virulence factors, frequently restricted to specific E.coli strains
Adherence / invasion by pathogenic E.coli
Six pathotypes of diarrhoeagenic E coli Enterotoxigenic E. coli(ETEC) EnteropathogenicE. coli(EPEC) EnteroaggregativeE. coli(EAEC) EnteroinvasiveE. coli(EIEC) Diffusely adherent E. coli(DAEC) Shiga toxin-producing E. coli(STEC)
Enterotoigenic E.coli
Important cause of bacterial diarrhoeal illness
Major cause of diarrhoea in lower-income countries, especially among children.
Leading cause of travelers’ diarrhoea
Faeco-oral transmission - faeces mixing with something that you eat or drink - prevalent in kids as fingers up bums and lack of hygiene
ETEC produces two toxins, a heat-stable toxin (ST) and a heat-labile toxin (LT).
Although different strains of ETEC can secrete either one or both of these toxins, the illness caused by each toxin is similar
Toxins stimulate the lining of the intestines causing them to secrete excessive fluid producing profuse watery diarrhoea and abdominal cramping
Less common -Fever, nausea with or without vomiting, chills, loss of appetite, headache, muscle aches and bloating
Onset 1-3 days after exposure and usually lasts 3-4 days.
Attaching and effacing of enterocytes by enteropathogenic E.coli (EPEC)
EPEC causes the localized effacement of microvilli and intimately attaches to the host cell surface, forming characteristic attaching and effacing (A E) lesions.
Intimate attachment requires the type III-mediated secretion of bacterial proteins, several of which are translocated directly into the infected cell, including the bac
Shiga toxin-producing E.coli (STEC)
Also known verocytotoxic E. coli(VTEC) or enterohemorrhagicE. coli (EHEC)
Most commonly identified STEC is E. coliO157:H7
First outbreak reported in 1982
Causes haemorrhagiccolitis (bloody diarrhoea) and haemolytic uraemic syndrome (HUS - triad of acute renal failure, haemolytic anemia, and thrombocytopenia)
Molecular action of Shiga toxin - B sub-units of Shiga toxins bind to globotriaosylceramide(Gb3) on host cell surface
After binding, the toxin is endocytosed and transported to the Golgi apparatus and the endoplasmic reticulum
During the intracellular transport, the A chain is cleaved into the small A2 fragment and the enzymatically active A1 fragment.
The A fragments are kept together by a disulfide bond until the toxin reaches the ER, where the A1 fragment is released and translocated into the cytosol
In the cytosol, the A1 part inactivates ribosomes thereby inhibiting protein synthesis, eventually resulting in cell death.
Extra intestinal pathogenic E.coli (ExPEC)
Strains of E coli capable of causing disease outside the intestinal tract
Due to the presence of wide range of virulence factors:
Adhesins - types of molecules that help bacteria stick to surfaces of cells
Iron acquisition systems - scavenge iron from the local environment
Protectins and invasins - that help protect against the immune response
Toxins - cause damage to local environment
Others
E.coli UTI’s
Urinary tract infections are very common in women but unusual in men
This difference is explained by anatomical differences between women and men
Uropathogenic E coli transfer from the rectum to the urethra and then migrate to the bladder, causing cystitis.
This journey is far easier in women than men
Not all UTI’s are caused by E.coli infections
Uropathogenic E.coli (UPEC)
Adhesins -
Type 1 fimbriae have adhesive tips that bind to α-D-mannosylatedproteins on uroepithelium, mediating adhesion, invasion of uroepithelium and the formation of intracellular bacterial communities (IBCs)
Toxins -
Lipopolysaccharide (LPS)
α-Haemolysin(HlyA) is a secreted, pore-forming toxin, cytotoxic towards epithelial cells in the urinary tract
Iron acquisition properties -
The availability of iron is extremely restricted in
the urinary tract
Bacteria produce their own iron-complexing
proteins (siderophores) to acquire iron.
E.Coli bloodstream infections
E coli bacteria are the commonest cause of bacterial bloodstream infection in England and the number of infections is rising.
In 2012-13:
32 309 cases; 30-day all-cause, mortality18.2%
In 2016-17:
40 580 cases; 30-day all-cause, mortality 14.8%
Around half of E coli bloodstream infections occur in patients older than 75 years
Causal factors -
50% UTIs -linked to ineffective antibiotic treatment???
21% of patients have urinary catheters - which massivly increases chances of UTI form skin bacteria
16% hepatobiliary infections
7% gastrointestinal infections
Interestingly in 2017-2018, the incidence of E coli bloodstream infection is around 50% higher in the north of England than the south of the country
And if you look at a correlation between infections of bloodstream E.coli infections and environmental temperature - both seem to increase in years 2011-2018 (peaks in summer, troughs in winter)
Postulated that due to increase in temperature - more people become dehydrated, which causes a build up of concentrated E.coli in the bladder (no water to reduce concentration) which can lead to blood stream infections - however this isn’t scientifically confirmed
Management of E.coli infections - diarrhoea
Prevention - avoid foods and drink that could be contaminated with bacteria: raw fruits and veg, raw seafood or undercooked meat, unpasteurised dairy products, untreated water in areas lacking adequate chlorination
Scientists found that sodium transport and glucose transport are coupled in the SI so that glucose accelerates absorption of solute and water, which can rehydrate without the need for IV fluids - saved a lot of children’s lives in not well off countries
Treatment - Most infected persons will recover within a few days, without requiring any specific treatment.
Clear liquids are recommended for persons with diarrhea to prevent dehydration and loss of electrolytes.
Oral rehydration solutions
Avoid antibiotics –may make illness worse - some strains of E.coli produce more toxins in presence of antibiotics
Antibiotic treatment of urinary tract infections
In UK, antibiotic treatment of UTIs is largely empirical
Commonly used antibiotics are trimethoprim and nitrofurantoin
Around 60% of E coli urine isolates tested in laboratories are trimethoprim resistant
Is the use of trimethoprim driving the increase in E coli bloodstream infections?
Or are the urine samples tested by laboratories unrepresentative of the majority of UTIs?
Antibiotic treatment of E coli bloodstream infections
Increasing resistance to a wide range of antibiotic classes
Resistance genes frequently on plasmids, therefore horizontal gene transfer common
Around 40-50% of isolates resistant to co-amoxiclav
Variable but increasing prevalence of carbapenemase genes.
Resistance linked to sequence type
