Escherichia coli or just E. Coli, is a gram-negative rod-shaped bacteria named after Dr.

Escherich
Theodor, who discovered it in feces, thus concluding that it colonizes the colon.

Alright, now E. Coli is gram-negative because its cell wall has a thin peptidoglycan layer so it cannot
retain the crystal violet stain, but instead, it stains pink with Safranin dye used during Gram staining.

So it looks like a little pink rod under the microscope.

Also, E. Coli is a catalase positive bacteria, and that means it produces an enzyme called catalase.

This can be tested by adding a few drops of hydrogen peroxide to a colony of bacteria, and catalase
makes hydrogen peroxide dissociate into water and oxygen, making the mixture foam.

E. Coli is also a lactose fermenter, because it can produce an enzyme called beta B-galactosidase that
cleaves lactose into glucose and galactose monomers.

To test this, E. Coli can be cultivated on lactose-containing media such as Phenol lactose, and as it
ferments it, the fermentation results in the production of acids that turn the red of phenol to yellow.

It is also a facultative anaerobe, meaning it lives in environments with or without oxygen.

Now, taking a closer look to this bacteria, E. Coli is encapsulated, meaning it’s covered by a
polysaccharide layer called a capsule.

E. Coli is a motile bacteria, because it has helical whip-like threads called flagella that it can use to move
around.

When E coli is cultivated on eosin methylene blue agar, it grows into black colonies with a greenish-black
metallic sheen.

Alright, most of E. Coli are harmless, and they can peacefully colonize the human gut without causing
any trouble.
However, some strains of E. Coli are pathogenic, meaning they can cause illness. It starts with this
bacteria using little thread-like extensions called fimbriae to attach to the host cell surface.

E coli has many different strains that can do that, and they cause different diseases. These strains can be
classified by two systems.

The first system uses serotypes, and it groups E. Coli strains based on their antigens.

Antigens are elements that the host’s immunity considers foreign and mount an immune reaction as a
response.

So, bacteria within a given serotype, trigger a similar immune response.

Alright, E. Coli has a number of antigens, and among them we have somatic antigens located just on the
cell membrane, and these ones are abridged with the letter “O”.

There are also capsular – “K” antigens located on the capsule, fimbrial – “F” antigens located on the
fimbria, and flagellar – “H” antigens located on the bacterial flagella.

Usually after this letter that tells on what part of the bacteria where the antigen is found, it follows a
designation number in case there are more antigens of the same kind, such as K1, K2, and so forth… E.
Coli antigens, influence its power to cause diseases, so that’s why they can alternatively be referred to
as virulence factors.

For example, E. Coli with capsular antigen one, or K1, are the ones that cause neonatal meningitis, while
an E. Coli that has an O157, and an H7 – designated as O157:H7, is associated with hemorrhagic colitis,
hemolytic uremic syndrome and diarrheal outbreaks.

Other E. Coli serotypes include E. Coli SE15, E. Coli F11, E. Coli O25:H and so on… but in fact, these
serotypes are so numerous and they can go up to 200 serotypes.

Thankfully, there’s a much simpler classification, and that is based on pathotypes.

A pathotype is a group of organisms of the same species, that cause disease in the same way - meaning
they use the same virulence factors.

And there are 5 E.Coli pathotypes: Shiga-like toxin-producing E.Coli, or STEC for short,

enterotoxigenic E. Coli or ETEC,

enteroinvasive E. Coli, or EIEC,

enteropathogenic E. Coli, or EPEC,

and uropathogenic E. coli or UPEC/

So first, Shiga-like toxin-producing E. Coli, or STEC is called that because it makes a toxin similar to the
one called Shiga toxin produced by Shigella.

STEC attaches to the host’s intestinal cells, and then start releasing toxins that cause injury to intestinal
epithelium and underlying blood vessels, resulting in inflammation.

This makes fluid and blood leak into the intestinal lumen, resulting in bloody diarrhea.

That’s why some people refer to it as enterohemorrhagic E. Coli, or EHEC.

But STECs can also affect the urinary tract, causing hemolytic uremic syndrome or HUS. Hemolytic
uremic syndrome usually develops after STEC have released their toxin into the bloodstream.

From the bloodstream, the toxin can get to the kidneys, and bind to the endothelial cells lining the
glomerulus, making them die by apoptosis, or programmed cell death.

Consequently, a dead endothelial cell leaves a gap in the capillary wall, and as more gaps keep forming,
it results in holes big enough to allow large molecules such as proteins to start leaking out of the
capillaries, resulting in proteinuria.

The destruction of endothelial cells triggers an inflammatory process in which inflammatory molecules
such as cytokines and chemokines are released.
Cytokines and chemokines activate blood platelets and initiate the clot formation.

As these platelets are used to form these clots their number in the blood decreases resulting in low
platelets or thrombocytopenia.

Also these clots can be big enough to obstruct small arterioles.

So, as red blood cells force to pass through obstructed micro-vessels, they can get sliced into fragments
called schistocytes in this process known as microangiopathic hemolysis.

So, as more red blood cells get destroyed in the process, their number reduces, which can cause anemia.

Alternatively, if clots obstruct too many arterioles, organs that depend on high blood flow, like the
kidney, may lack blood and die by ischemia.

Now, an ischemic kidney is unable to filter blood. This is how too much of metabolic wastes such as
urea, start accumulating in the blood, leading to uremia.

Then HUS is a combination of hemolytic anemia, when red blood cells are being overly destroyed,
kidney failure due to the destroyed glomerular cells that results in uremia or high levels of blood urea,
and thrombocytopenia, meaning low platelets.

Ok, next up, there’s enterotoxigenic E. Coli or ETEC. After using its fimbriae to attach to the intestinal
mucosa, it starts releasing two types of enterotoxins: heat-labile enterotoxin, which is easily destroyed
by heat, and heat stable enterotoxin which is not easily destroyed by heat.

Both of these toxins cause intestinal inflammation, which leads to a lot of fluid being secreted in the
intestinal lumen, causing watery diarrhea.

But there’s usually no intestinal wall destruction, and as a result, no bleeding.

In contrast, enteroinvasive E. Coli, or EIEC, attaches to the intestinal epithelium and then it mechanically
destroys and invades the intestinal epithelial cells, and multiplies intracellularly.

This triggers a widespread destructive inflammatory response in the intestines that may result in bloody
diarrhea

Next up, there’s enteropathogenic E. Coli, or EPEC, and for unknown reasons, this one almost exclusively
causes disease in children under 2 years of age.

EPEC also attaches to the intestinal epithelium and invades the intestinal epithelial cells.

Then, through an unknown mechanism, it destroys the cell cytoskeleton, which is the intracellular
framework responsible for maintaining the shape of the cell.

This makes the intestinal epithelial cells flatten, which impairs their ability to absorb water and
nutrients, resulting in watery diarrhea.

And lastly, there’s uropathogenic E. coli or UPEC, that causes about 90% of all community acquired
urinary tract infections, or UTIs, and roughly 50% of hospital-acquired UTIs.

UPEC usually live peacefully in the gastrointestinal tract without causing any harm.

However, if they get out of the colon, like following defecation, and colonize the perineum, they may
ascend from the perineum, up the urethra and reach the urinary bladder, causing cystitis.

On the urinary epithelium, these bacteria produce alpha- and beta-hemolysins, which cause lysis of
urinary tract cells.

They can also move up the ureters and infect the kidneys, causing pyelonephritis.

Symptoms depend on the disease and the infecting pathotype

So right off the bat, all pathotypes except for UPEC cause diarrhea, and are associated with abdominal
cramps and vomiting.

With STEC, there’s bloody diarrhea, and there may be a low-grade fever.

If things progress to hemolytic-uremic syndrome, there may be body swelling, confusion, nausea and
vomiting.

In addition to that, there can be paleness of the eyes’ conjunctiva due to anemia, jaundice that results
from buildup of bilirubin that result from hemolysis, diarrhea and abdominal pain.

With EIEC, there may also be bloody diarrhea, and chills.

With the remaining pathotypes, EPEC, and ETEC, there’s usually non-bloody diarrhea.

EPEC causes severe dehydration in children under 2, and may cause prolonged or chronic diarrhea,
which may lead to malnutrition, or stunted growth.

ETEC causes large amounts of watery diarrhea, and there may also be fever, and bloating. Finally,

UPEC causes UTI symptoms like dysuria, which is pain during urination, urinary frequency, and, if the
kidney is affected, there may be flank pain.

Now, in general, it’s hard to diagnose an E. Coli serotype or pathotype because it requires a series of
complex tests.

But to diagnose E. Coli in general, Gram-staining can be done on a stool or urine sample, and cultures on
eosin methylene blue agar can be done to confirm the diagnosis.

HUS can be confirmed by identifying shiga toxin in the blood.

Treatment for diarrhea usually consists of hydration and rest. Antibiotics are not routinely used, but
doxycycline or cotrimoxazole, which is the combination of Trimethoprim and Sulfamethoxazole can be
given in severe cases.

For hemolytic uremic syndrome, supportive care, including dialysis, corticosteroids, blood transfusions,
and plasmapheresis or the exchange of the affected blood plasma with a new unaffected one from a
donor.

UTIs are treated with antibiotics such as cotrimoxazole,

nitrofurantoin,

or fluoroquinolones like ciprofloxacin.

Summary

Alright, as a quick recap, Escherichia coli are gram-negative, rod-shaped, encapsulated, facultative
anaerobic, catalase positive, lactose fermenting bacteria.

Even though some E. Coli might become pathogenic, most of the time they colonize the gut harmlessly.

The pathogenic E. Coli are classified into four main pathotypes namely; STEC, which particularly causes
hemorrhagic diarrhea, and hemolytic uremic syndrome, ETEC, which is commonly associated with
watery diarrhea, EIEC which causes bloody diarrhea by mechanically damaging the intestinal epithelium,
EPEC which causes diarrhea in children below 2 years, and finally UPEC which cause most of the UTIs.

E. Coli is usually diagnosed using a gram stain and a microscopic examination followed by a bacteria
culture.

Treatment of diarrhea consists of supportive measures like rehydration, and sometimes antibiotics are
used.

Hemolytic uremic syndrome may require complex treatment measures, like dialysis, corticosteroids,
blood transfusions and plasmapheresis.
UTIs are treated with antibiotics such as cotrimoxazole, nitrofurantoin, or fluoroquinolones like
ciprofloxacin
Salmonella is a bacterium belonging to the family Enterobacteriaceae.

There are two main species: Salmonella bongori and Salmonella enterica, and the latter has six
subspecies.

One of the subspecies is enterica, which has over 2500 serotypes that can be divided into two main
groups based on the clinical symptoms they cause- so typhoidal or non-typhoidal Salmonella.

The non-typhoidal group, can infect humans and animals and cause a variety of disease states.

But, the most common serotype, Salmonella enteritidis, causes intestinal inflammation, called
gastroenteritis, or commonly called “food poisoning”.

OK, but generally, Salmonella are encapsulated gram-negative, rod bacteria – meaning, they have a
polysaccharide layer outside the cell envelope and look like little red or pink sticks on a gram stain.

They’re facultative intracellular pathogens, meaning they can live both outside or inside of its host’s
cells.

And have flagella, making them motile, but don’t form spores.

They’re also facultative anaerobes, so they can undergo respiratory and fermentative metabolism; and
they can ferment glucose but not lactose; are oxidase negative, and produce hydrogen sulfide gas.

And while a variety of media can be used to selectively identify Salmonella, among them is Triple Sugar
Iron agar which produces a black precipitate when hydrogen sulfide is produced.

Now, once Salmonella is ingested and reaches the distal ileum of the small intestine, it tends to target
the epithelial layer of the mucosal lining where it uses surface appendages to adhere to microfold cells,
or M-cells.
And these M-cells eat, or phagocytose, the bacteria from the intestinal lumen and spit it out into the
underlying Peyer’s patches - a type of mucosal immune tissue that extends into the submucosa.

When encountering non-typhoidal Salmonella, the immune system responds strongly by releasing
proinflammatory cytokines that recruit additional immune cells, particularly neutrophils.

This causes inflammation of the small intestines and the colon, called enterocolitis.

Responding immune cells can also damage the mucosa as they travel to the site of infection.

This can cause ulcers; and gastrointestinal tract dysfunction that leads to an efflux of water and
electrolytes into the intestinal lumen, which causes diarrhea.

Now, usually, the infection is uncomplicated and limited to the mucosa, where it’s often destroyed by
the local immune cells.

But, in some cases, the infection can become invasive, gaining access to nearby blood vessels, causing
bacteremia.

From the bloodstream, the bacteria can spread to other organs like the brain, bones, liver, or spleen.

Now, reservoirs for non-typhoidal Salmonella include infected humans and animals, particularly birds,
reptiles, mammals, and amphibians.

So, transmission can be fecal-to-oral and foodborne through consumption of contaminated raw or
undercooked animal products; especially poultry, meat, and eggs, or unpasteurized milk or milk-
products.

Transmission can also occur through any contaminated consumable like water; fruits and vegetables;
and even peanut butter.
Finally, the infection can also spread through direct contact with infected animals, if contaminated
hands then reach the mouth.

Now, because Salmonella is sensitive to gastric acid, a large inoculum, meaning more than 100,000
microorganisms, is needed to cause an infection.

But certain factors; like being a young child, an older adult, having low gastric acidity, or being
immunocompromised can cause an elevated risk of infection and development of invasive, complex
cases.

Now, sometimes symptoms can be absent, even if a host is infected and a carrier capable of spreading
non-typhoidal Salmonella.

When symptoms do occur, they start 24 to 48 hours, and they’re pretty typical for food poisoning:
watery diarrhea, which may be bloody; abdominal cramps; nausea and vomiting; headache; chills; and a
low-grade fever, which typically resolves within 2 days.

Dehydration may also occur if fluid loss from diarrhea has not been replenished.

A definitive diagnosis can be made with a stool culture on selective media.

In invasive infections, additional cultures; like blood and bone marrow aspirate cultures may be
necessary.

Treatment involves managing symptoms, particularly fluid and electrolyte replenishment for diarrhea,
suppressing nausea, and alleviating pain.

Antibiotics are typically not indicated for uncomplicated infections since infections tend to be self-
limiting, and antibiotics can prolong a carrier state or even cause relapse.

However, antibiotics are usually given in invasive infections, especially in complicated cases like in
immunocompromised individuals, and antibiotic selection is made based on sensitivity of the particular
infecting strain.
Finally, an important part of treatment is practicing good hygiene and sanitation, including proper food
and hand washing, and thoroughly cooking raw foods.

Summary

So, to recap: Salmonella is a rod-shaped, gram-negative bacteria of the Enterobacteriaceae family.

After ingestion, Salmonella tends to infect M-cells of the small intestine epithelial mucosa, which
transfer the bacteria to the underlying Peyer’s patches.

Serotypes that are non-typhoidal elicit a strong proinflammatory response which causes inflammation of
the small intestine and colon.

Infections are usually foodborne from contaminated sources or from interactions with animal reservoirs,
and cause the hallmark symptoms of “food poisoning”, including abdominal cramps, vomiting,
headaches, fever and diarrhea.

Diagnosis can be made with a stool culture, and treatment is typically fluid and electrolyte
replenishment, especially in uncomplicated or non-invasive cases.

But in complicated, invasive infections, antibiotic therapy may be necessary.

Salmonella is a bacterium belonging to the family Enterobacteriaceae.

There are two main species: Salmonella bongori and Salmonella enterica, which itself has six
subspecies.

One of the subspecies is enterica, which has over 2500 serotypes that can be divided into two
main groups based on the clinical symptoms they cause typhoidal or non-typhoidal Salmonella.

The typhoidal group, which includes serotype Salmonella typhi (S. typhi), specifically infects
humans and causes enteric fever, which is more commonly called typhoid fever.

If left untreated, it can be fatal and throughout history, has been the cause of death of aviator and
engineer Wilbur Wright, one of the Wright brothers; Dr. Hashimoto, the first to describe
Hashimoto's thyroiditis; and several people in New York City infected by “Typhoid Mary” in the
first documented asymptomatic carrier of the disease in the United States.

OK, but generally, Salmonella are encapsulated gram-negative, rod bacteria – meaning, they
have a polysaccharide layer outside the cell envelope and look like little red or pink sticks on a
gram stain.

They’re facultative intracellular pathogens, meaning they can live both outside or inside of its
host’s cells.

And have flagella, making them motile, but don’t form spores.

They’re also facultative anaerobes, so they can undergo respiratory and fermentative
metabolism; and they can ferment glucose but not lactose; are oxidase negative; and produce
hydrogen sulfide gas.

And while a variety of media can be used to selectively identify Salmonella, among them is
Triple Sugar Iron agar which produces a black precipitate when hydrogen sulfide is produced.

Now, once Salmonella is ingested and reaches the distal ileum of the small intestine, it targets the
epithelial layer of the mucosal lining.
Here, it uses surface appendages to adhere to microfold cells, or M-cells. And these M-cells eat,
or phagocytose, the bacteria from the intestinal lumen and spit it out into the underlying Peyer’s
patches - a type of mucosal immune tissue that extends into the submucosa.

And, well, S. typhi has a Vi capsular polysaccharide antigen virulence factor, which helps protect
the bacteria from being tagged with antibodies that signal leukocytes like neutrophils to come in
and phagocytose the bacteria.

Moreover, neutrophil recruitment is also suppressed.

On the other hand, the recruitment of monocytes and macrophages is induced, making them the
primary cells that respond to the infection.

And as they are recruited to the infection site, they cause hypertrophy and necrosis of the
surrounding tissues; which can damage the epithelial lining, and potentially lead to ileal
perforation, consequently, a secondary infection of the peritoneum.

Now, aside from that, macrophages also phagocytose S. typhi, so the bacteria is slowly engulfed
by the cell membrane, which invaginates to form a sac on its inner side.

The sac then separates from the actual cell membrane forming what’s referred to a Salmonella-
containing vacuoles.

Normally, the vacuole would fuse with the host cell’s lysosomes, which are organelles filled with
digestive enzymes that destroy the bacteria.

But, S. typhi uses needle-like protein appendage, called a Type III secretion system, to inject a
variety of effector proteins across the vacuole membrane and into the host cell’s cytoplasm.

This leads to a remodeling of the vacuole that prevents fusion with the lysosome, so S. typhi
survives and replicates within the vacuole.

All the while, S. typhi is using the host macrophage to hitch a ride to the nearby lymphatic
vessels that drain into local mesenteric lymph nodes.
Once there, the macrophage can continue to flow through the thoracic duct and into systemic
lymphatic circulation where they can enter reticuloendothelial tissues in the liver, spleen, bone
marrow, gall bladder and additional lymph nodes.

At about this point, S. typhi can induce macrophage apoptosis, or cell death, so the bacteria is
released into the bloodstream, called bacteremia.

Bacteremia can progress to sepsis, an acutely life-threatening condition characterized by

systemic vasodilation and hypoperfusion of vital organs - which means the organs aren’t getting
enough nutrient and oxygen-rich blood.

Another complication can arise in individuals with spleen issues, because the spleen plays an
important role in immunity against encapsulated bacteria.

This includes people who have undergone a splenectomy, or spleen removal, or those with sickle
cell disease, who have functional asplenia.

In these individuals, S. typhi can cause osteomyelitis, which is an acute infection of the bones.

On the other hand, some people can become chronically infected with S. typhi, and that means
they are carriers for the bacteria for decades or a lifetime, even after symptoms have resolved.

In these cases, S. typhi typically remains in the gallbladder, and is periodically swept along with
bile through the bile duct to the intestines, where it can be excreted in feces.

Now, S. typhi is uniquely adapted and restricted to only infect humans, who are also the only
known reservoir; and its route of transmission is fecal to oral - even if the feces come from a
currently asymptomatic host.

So, transmission is usually linked to any contact between contaminated hands or objects and the
mouth, and also to poor sanitation and poor hygiene that leads to consuming contaminated water
or food, especially if prepared with unwashed hands.

It also seems to be particularly endemic to Asia, Africa, Latin America, and the Caribbean.
Finally, S. typhi is sensitive to gastric acids, so half of the time, it takes a large inoculum, of
around 100,000 microorganisms, to cause an infection

Now, symptoms of typhoid fever first appear about 1-2 weeks after initial infection, and can take
4-6 weeks to resolve.

Typically, there’s a high, sustained fever, abdominal pain, constipation followed by diarrhea, and
rose or salmon-colored spots on the chest and abdomen.

Hepatomegaly and splenomegaly may also occur as the infection spreads.

Dehydration, weakness, headaches, and an overall cloudy or confused mental state can occur,
especially in advanced cases.

Diagnosis can be confirmed with cultures from blood; intestinal secretions, like vomit or a
duodenal aspirate; or stool cultures, which can identify S. typhi, particularly in the first week of
infection.

For asymptomatic carriers, bile cultures are the most effective diagnostic tool because the
bacteria can be absent from stool.

Treatment involves managing symptoms, particularly fluid and electrolyte replenishment for
diarrhea and non-steroidal anti-inflammatory drugs for pain and fever.

Commonly, broad-spectrum antibiotics are used, like fluoroquinolones or cephalosporins, like

ceftriaxone.

Even though antibiotics can prolong the excretion of bacteria in feces.

For carriers, a combination of antibiotic therapy with fluoroquinolones and surgical removal of
the gallbladder is the most effective form of treatment.
Finally, an important part of treatment is practicing good hygiene and sanitation to limit the
spread to uninfected individuals.

Prophylaxis is available in the form of an inactivated intramuscular vaccine containing the Vi

capsular polysaccharide, or a live oral vaccine.

Summary
So, to recap: Salmonella is a rod-shaped, gram-negative bacteria of the Enterobacteriaceae
family.

After ingestion, Salmonella tends to infect M-cells of the small intestine epithelial mucosa,
which transfer the bacteria to the underlying Peyer’s patches.

Serotypes that are typhoidal evade and dampen the immune response, and use host macrophages
to systematically spread through the lymphatic system and bloodstream.

Symptoms include a high fever with constipation followed by diarrhea, salmon-colored spots on
the abdomen, and abdominal pain.

A carrier state exists in which the bacterium colonizes the gallbladders of people with the disease
so they continue to excrete bacteria in their feces.

Treatment can include ceftriaxone or a fluoroquinolone, but antibiotics can prolong fecal
excretion of the pathogen.

Vaccines exist, with an oral, live attenuated vaccine, and an intramuscular vaccine containing Vi
capsular polysaccharide.
 Progression of illness
Week 1
 Body temperature rises gradually.
 Relative bradycardia 
 Constipation or diarrhea 
 Headache
Week 2
 Persistent fever , but no chills; mostly unresponsive to antipyretics
 Rose-colored spots: a small, speckled, rose-colored exanthem that appears on
the lower chest and abdomen (most commonly around the navel) in approx. 30% of
affected individuals 
 Typhoid tongue: greyish/yellowish-coated tongue with red edges
 Nonspecific abdominal pain and headache
 Yellow-green diarrhea, comparable to pea soup (caused by purulent,
bloody necrosis of the Peyer patches), or obstipation and bowel obstruction (as a
result of swollen Peyer patches in the ileum)
 Neurological symptoms (delirium, coma) the toxin can cross the bbb causing
Week 3
 Clinical features of week 2
 Additional possible complications include:
o Gastrointestinal ulceration with bleeding and perforation 
o Hepatosplenomegaly
o In rare cases: sepsis, meningitis, myocarditis, and renal failure

Diagnostics
 Laboratory tests
o Anemia
o Leukopenia in adults or leukocytosis in children  
 Absolute eosinopenia  [5]

 Relative lymphocytosis  [6]

o Abnormal liver function tests

 Pathogen detection  [3]

o Blood cultures: Bacteremia is detectable starting in week 1 of the disease. 

o Stool cultures 
 o Bone marrow cultures   [7]

o Serology (Widal test) 
Blood culture is the most important diagnostic tool at disease onset, as stool
cultures are often negative despite active infection.

Treatment
 First-line treatment: fluoroquinolones (e.g., ciprofloxacin)
 Azithromycin, if resistance to fluoroquinolones is suspected (e.g., in patients with
infection acquired from certain regions, such as South Asia)
 Third-generation cephalosporins (e.g., ceftriaxone) are preferred for severe
infection.
 Antibiotics prolong the duration of fecal excretion of bacteria.