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Enterobacteriaceae
Meningitis
Opportunistic pathogens
Pneumonia
Escherichia coli
Klebsiella pneumoniae
Sepsis
Enterobacter aerogenes
Serratia marcescens
Diarrhea
Proteus spp.
Providencia spp.
Citrobacter spp.
Obligate pathogens
Salmonella spp.
Shigella spp.
Yersinia spp.
Some E. coli strains
UTI
Morphology and Physiology
Short gram-negative rods.
Facultative anaerobes.
Grow readily and rapidly
on simple media.
K. pneumoniae
Klebsiella spp. have large capsule
(form large and very mucoid
colonies); those of Enterobacter
have smaller capsule; the others
produce diffusible slime layers
(form circular, convex and smooth
colonies).
Some enteric bacteria are
motile. Klebsiella species are
not motile, while Proteus
species move very actively by
means of peritrichous flagella,
resulting in "swarming" on solid
medium.
Some strains of E. coli
produce hemolysis on blood
plates.
Proteus spp.
Enterobacteriaceae is characterized biochemically by the
ability to reduce nitrates to nitrites and to ferment glucose.
Cytochrome oxidase-negative.
Enterobacteriaceae species differ in their ability to ferment
lactose. Some ferment lactose rapidly, some does it slowly
and the others (e.g., Salmonella and Shigella) do not
ferment lactose at all.
Some Enterobacteriaceae pathogens (e.g., Salmonella and
Shigella) are resistant to bile salts, and this property can be
used to select them from commensal organisms that are
inhibited by bile salts.
Antigenic Structure
O antigens
O-specific polysaccharides located in LPS. Heat-stable and
resistant to alcohol. A single organism may carry several O
antigens.
(Core polysaccharide of LPS: enterobacterial common antigen,
ECA.)
K antigens
External to O antigens in some strains. Mostly are capsular
antigens (polysaccharides). K antigens of Klebsiella can be
identified by capsular swelling test.
H antigen
Flagellin. Heat-labile and denatured by alcohol. May be absent
or undergo phase variation in different species.
ECA
Pathogenesis and Immunity
Common virulence factors
Endotoxin (Lipid A of LPS)
Capsule
Antigenic phase variation
Acquisition of growth factors (e.g. Fe)
Resistance to serum killing
Antimicrobial resistance
Type III secretion systems: possessed by some Enterobacteriaceae
pathogens, e.g., E. coli, Yersinia, Salmonella, and Shigella; facilitate
transport of bacterial virulence factors directly into host cells.
Toll-like
receptor 4
(TLR-4)
Pathogenesis of sepsis caused
by gram-negative bacteria
Pathophysiological effects of LPS
Activation of complement, release of cytokines,
fever, leukocytosis, thrombocytopenia, impaired
organ perfusion and acidosis, disseminated
intravascular coagulation (DIC), hypotension,
shock and death, premature labor and abortion.
Escherichia coli
Pathogenesis and clinical diseases
Sepsis
For people with inadequate host defenses, e.g. the newborns.
Usually originates from UT or GI infections. Some infections
may be endogenous.
Meningitis
E. coli (particularly
K1 strains) and
S. agalactiae are
the leading causes
of meningitis in
infants.
Bacteremia
Escherichia coli
Pathogenesis and clinical diseases
Urinary tract infection
E. coli is the most common cause of urinary tract infection.
Community- vs. hospital-acquired UT infection
Most infections originate from colon; the bacteria
contaminate the urethra, ascend into the bladder, and may
migrate into the kidney or prostate.
Symptoms: urinary frequency, dysuria, hematuria, and
pyuria. Can result in bacteremia and sepsis.
Uropathogenic E. coli strains produce P (Pyelonephritisassociated) pili, which is associated with renal colonization
and may induce protective immunity, and hemolysin HlyA.
Escherichia coli
Pathogenesis and clinical diseases
EAST & PET
Gastroenteritis
(Diarrhea)
Caused by various virotypes:
Enterotoxigenic E. coli
Enteropathogenic E. coli
Enterohemorrhagic E. coli
Enteroinvasive E. coli
Enteroaggregative E. coli
Table 30-2
Escherichia coli
Pathogenesis and clinical diseases
Enterotoxigenic E. coli (ETEC): major causal agent of Traveler's
diarrhea.
These strains express:
a) Heat-labile (LT-1) enterotoxins: an A-B toxin. Subunit A causes
intense and prolonged hyper secretion of chloride ions and inhibits
the reabsorption of sodium and chloride. The gut lumen is distended
with fluid, and hypermotility and secretory diarrhea occur, lasting for
several days. It stimulates the production of neutralizing antibodies,
and cross-reacts with the enterotoxin of Vibrio cholerae.
b) Heat-stable (STa) enterotoxin: also stimulates fluid secretion;
poorly immunogenic; short onset.
c) Colonization factors (CFAs): facilitate the attachment of E. coli
strains to intestinal epithelium. Usually are pili in nature.
ADP-ribosylation
Enhance chloride
secretion
Decrease sodium and
chloride absorption
Escherichia coli
Pathogenesis and clinical diseases
Enteropathogenic E. coli (EPEC): causes infant diarrhea in
poor countries. Watery diarrhea results from malabsorption due
to microvilli destruction. Spread by person-to-person contact.
Enteroinvasive E. coli (EIEC): closely related to Shigella
in pathogenic properties.
Enteroaggregative E. coli (EAEC): causes chronic diarrhea
and growth retardation in infants in developing countries.
Diffusely adherent E. coli (DAEC): causes watery diarrhea
in infants.
Escherichia coli
Pathogenesis and clinical diseases
Enterohemorrhagic E. coli (EHEC)
The most common strains producing disease in developed countries.
These strains are associated with hemorrhagic colitis and hemolytic
uremic syndrome (HUS: acute renal failure, microangiopathic
hemolytic anemia and thrombocytopenia; 5-10% infected children).
Serotpe O157:H7 is most commonly isolated.
Cattle is a reservoir, and hamburger, unpasteurized milk, fruit juices,
and uncooked vegetables are common sources of human infection.
Induces A/E lesions on enterocytes. Diarrhea and HUS may be
associated with the Shiga toxins, which are A-B toxins that bind to
28S rRNA and disrupt protein synthesis.
Other opportunistic Enterobacteriaceae
Klebsiella
K. pneumoniae and K. oxytoca are the most commonly isolated.
Can cause community-acquired primary lobar pneumonia
(frequently involves necrotic destruction of alveolar space), and
infections of wound, soft tissue, and urinary tract.
Risk factors for pneumonia: alcoholism; compromised pulmonary
function.
*In Taiwan: liver abscess is commonly seen in infection by K.
pneumoniae.
K. granulomatis may cuase granuloma inguinale, a sexually
transmitted disease, in some countries.
K. rhinoscleromatis: granulomatous disease of the nose.
K. ozaenae: chronic atrophic rhinitis.
Proteus
Most common isolates: P. mirabilis.
Cause urinary tract infections and bacteremia.
Produce urease, making the urine of the patients of UT
infection with Proteus alkaline, promoting stone formation
by precipitating Mg and Ca.
Enterobacter, Citrobacter, Morganella, Serratia
Opportunistic pathogens causing nosocomial infections in
neonates and immunocompromised patients.
These genera, particularly Enterobacter, are resistant to
multiple antibiotics.
Escherichia coli and other
opportunistic Enterobacteriaceae
Laboratory diagnosis
Smears: the Enterobacteriaceae pathogens resemble each
other. The presence of large capsules is suggestive Klebsiella.
Culture: blood agar and selective differential media (e.g.,
MacConkey agar), the latter is useful for preliminary
identification. Commercial biochemical test systems can be
used for identification of Enterobacteriaceae members.
Serologic tests are used for determining the clinical significance
of an isolate and for epidemiologic purpose.
E. coli and other opportunistic
Enterobacteriaceae
Treatment
Variation in drug susceptibility is great, and antibiotic
sensitivity tests are essential.
Diarrhea patients usually need only symptomatic relief.
Antibiotic treatment may prolong the fecal carriage or
increase the risk of secondary complications.
Treatment of bacteremia and septic shock: prompt
antibiotic treatment, restoration of fluid and electrolyte
balance, and treatment of disseminated IV coagulation.
E. coli and other opportunistic
Enterobacteriaceae
Prevention and control
Enterobacteriaceae are a major part of normal flora and
a common contaminant of the environment.
In hospitals, opportunistic Enterobacteriaceae are
commonly transmitted by personnel, instruments, or
parenteral medications. Their control depends on hand
washing, rigorous asepsis, sterilization of equipment,
disinfection, restraint in IV therapy, and strict precautions
in keeping the urinary tract sterile.
Salmonella
Salmonella spp. do not ferment lactose.
Most species of Salmonella are motile with peritrichous flagella.
Some Salmonellae have capsular antigens; that of S. Typhi is
referred to as Vi antigen.
Groups and species of Salmonella are identified by serologic
analysis of O and H antigens (> 2,500 serotypes). Classification of
salmonellae is traditionally based on serogrouping and serotyping
(e.g. S. typhimurium, which is reclassified as S. enterica together
with most human pathogens by analysis of DNA homology). The
correct name for S. typhi is S. enterica, serovar. Typhi or S. Typhi.
They can be identified by biochemical tests and serogrouping, with
follow-up serotyping confirmation.
Salmonella
Epidemiology
S. Typhi and S. Paratyphi are primarily infective for humans.
Other salmonellae are chiefly pathogenic in animals (poultry, pigs,
rodents, cattle, pets etc.) that constitute the reservoir for human
infection.
Humans usually become infected by ingestion of contaminated food
or drink (mean infective dose: 106-108, but that of S. typhi is lower).
In children, infections can result from direct fecal-oral spread.
The most common sources of human infections: poultry, eggs, dairy
products, and foods prepared on contaminated work surfaces.
However, the major source of infection for enteric fever is the
carriers (convalescent or healthy permanent).
Salmonella
Pathogenesis and Immunity
Invasion
Acid tolerance response (ATR) gene protects the organism
from gastric acid.
The bacteria invade into (by inducing membrane ruffling)
and multiply in the M cells of the small intestine.
Inflammatory response confines the infection to the GI tract.
Survival in macrophages
Salmonellae are facultative intracellular pathogen.
* Invasion and survival in macrophages are mediated by
genes located in PAI (pathogenicity island)-1 and PAI-2,
respectively.
Salmonella
Clinical diseases
1. Enteritis
Incubation period: 6-48 hours.
Symptoms: nausea, headache, vomiting, nonbloody
profuse diarrhea, with few leukocytes in the stools. Lowgrade fever, abdominal cramp, myalgia, and headache
are also common. Episode resolves in 2-7 days.
Inflammatory lesions of the small and large intestine are
present. Stool cultures remain positive for several weeks
after clinical recovery.
Salmonella
Clinical diseases
2. Bacteremia
Most common causal species: S. Choleraesuis, S Typhi
and S. Paratyphi.
Symptoms: like sepsis caused by other gram-negative
bacteria. 10% of patients may have localized suppurative
infections, e.g., osteomyelitis, endocarditis, arthritis, etc.
High risk population: pediatric and geriatric patients;
AIDS patients.
Salmonella
Clinical diseases
3. Enteric fever (typhoid fever)
Causal species: S. Typhi, S. Paratyphi A, S. Schttmuelleri,
and S. Hirschfeldii.
Mouth
small intestine
lymphatics and bloodstream
infect liver, spleen and bone marrow
multiply and
pass into the blood
second and heavier bacteremia
onset of clinical illness
colonization of gallbladder
invasion of the intestine
typhoid ulcers and severe
illness.
Chronic carriers (1%-5% of patients): bacteria persist in the
gallbladder and the biliary tract for more than one year.
Symptoms: incubation time: 10-14 days. Gradually
increasing fever, malaise, headache, myalgias, and
anorexia, which persist for a week or longer.
In severe cases: intestinal hemorrhage and perforation.
Principal lesions: hyperplasia and necrosis of lymphoid
tissue, hepatitis, focal necrosis of the liver, and
inflammation of the gallbladder, periosteum, lungs and
other organs.
Salmonella
Treatment
Enteric fever and bacteremia require antibiotic treatment:
chloramphenicol, ampicillin, trimethoprim-sulfamethoxazole.
Surgical drainage of metastatic abscesses may be required.
Salmonella enterocolitis needs only supportive therapy
(antibiotic treatment may prolong the symptoms and
excretion of the salmonellae). Drugs to control hypermotility
of the gut should be avoided because it is easy to transform
a trivial gastroenteritis into a life-threatening bacteremia by
paralyzing the bowel.
Chronic carriers of S. Typhi may be cured by antibiotics alone
or combined with cholecystectomy.
Salmonella
Prevention and control
Sanitary measures.
Carriers must not be allowed to work as food
handlers.
Strict hygienic precautions for food handling.
Vaccines against S. Typhi:
Purified Vi antigen
Oral, live attenuated vaccine.
National salmonella death toll rises to 7
(Staff writer Ridgely Ochs contributed to this story. January 24, 2009)
A seventh death was linked Friday to a nationwide outbreak of salmonella
associated with tainted peanut butter and paste sourced to the Peanut
Corp. of America's plant in Blakely, Ga., authorities confirmed.
Although their exact causes of death have not been determined, all seven
people have died after being infected with the bacterial strain Salmonella
Typhimurium, the Centers for Disease Control and Prevention said on its
Web site.
There have been 493 cases reported in 43 states and one Canadian
province of people sickened, though authorities stress the numbers
sickened are likely far in excess of that as many cases go unreported.
Known patients ranged in age from 1 to 98, and 22 percent of the those
have been hospitalized.
Another 10 firms Friday recalled products that use PCA peanut butter or
paste - bringing to roughly 360 the number of products affected - as it
emerged that the Peanut Corp. of America's plant in Blakely, Ga. laid off
most of its roughly 50 workers. The outbreak has triggered a
congressional inquiry and renewed calls for reform of food safety laws.
http://www.newsday.com/services/newspaper/printedition/saturday/health/ny-lisalm246010666jan24,0,5876138.story
Shigella
S. dysenteriae, S. flexneri , S. sonnei , & S. boydii: bacillary dysentery
> 45 O serotypes; have no H antigen; do not ferment lactose.
Pathogenesis and Immunity
Shigellosis is primarily a pediatric disease, and is restricted to the GI
tract.
Mean infective dose: 103.
Mouth
colon
invade M cells and subsequently spread to
mucosal epithelial cells
cause microabscess in the wall of colon
and terminal ileum
necrosis of the mucous membrane,
superficial ulceration, bleeding, and formation of pseudomembrane.
Shiga toxin
An A-B toxin inhibiting protein synthesis.
Damages intestinal epithelium and glomerular endothelial cells
(associated with HUS) .
Destablize the
intestinal wall
Activates the invasion genes
on the virulence plasmid
M cell
Attracted by
the cytokines
released by
macrophage
Internalized shigellae induce
apoptosis of macrophage
and release of the bacteria
Shigella
Clinical diseases
Incubation period: 1-3 days
Sudden onset of abdominal pain, fever and watery diarrhea
number of stools increase, less liquid, often contain mucus
and blood, rectal spasms with resulting lower abdominal pain
(tenesmus)
symptoms subside spontaneously in 2-5 days
in adult cases, but loss of water and electrolytes frequently
occur in children and the elderly
a small number of
patients remain chronic carriers.
Some cases were accompanied by hemolytic uremic
syndrome (HUS).
Shigella
Laboratory diagnosis
Specimens: fresh stool, mucus flecks, and rectal
swabs. Large numbers of fecal leukocytes and some
RBC may often be seen microscopically.
Culture: differential and selective media as used for
salmonellae.
Treatment
Antibiotic treatment: chloramphenicol, ampicillin,
tetracycline, and trimethoprim-sulfamethoxazole.
Drug resistance is common.
Opiates should be avoided.
Shigella
Prevention and control
Humans are the only reservoir for shigellae.
Transmission of shigellae: water, food, fingers, feces,
and flies.
Most cases occur in children under 10 years of age.
Prevention and control of dysentery:
1. Sanitary control of water, food and milk; sewage
disposal; and fly control.
2. Isolation of patients and disinfection of excreta.
3. Detection of subclinical cases and carriers.
Yersinia
Y. pestis: plague ("black death")
Y. pseudotuberculosis and Y. enterocolitica: gastroenteritis
Grows more rapidly in media containing blood or tissue fluids
and fastest at 30 oC. Some species (e.g. Y. enterocolitica) can
grow in refrigerated food.
Pathogenesis
The Yersinia pathogens are able to resist phagocytic killing by
secreting proteins into the phagocyte and result in inhibition of
killing by phagocyte, apoptosis of macrophage, and suppression
of cytokine production.
Y. pestis produces a protein capsule (Fraction 1), and Pla
(plasminogen activator protease) that degrades C3b and C5a,
and fibrin clot (enhances spread of bacteria into blood stream).
Yersinia pestis
Causes zoonotic infections; humans are accidental hosts.
Three major pandemics have occurred in 541 AD, 1320s and 1860s.
Two forms of infections:
Urban plague
Rats as natural reservoirs.
Spread among rats or between rats and humans by infected flea.
Can be eliminated by effective control of rats and better hygiene.
Sylvatic plague: infections of rodents and domestic cats.
Y. pestis are widely distributed in mammalian reservoirs and flea
vectors and produces fatal infections in animal reservoirs.
Human infections are acquired by contacting the reservoir
population.
Yersinia pestis
Pathogenesis
Bubonic plague
Y. pestis enters a flea when it feeds on an infected animal
the
bacteria multiply in the gut of the flea
flea becomes hungry and
bites ferociously
Y. pestis passes from the flea into the bite
wound
the bacteria are phagocytised, but can multiply
intracellularly or extracellularly
reach the lymphatics, and an
intense hemorrhagic inflammation develops in the enlarged lymph
nodes, which may undergo necrosis
Y. pestis may reach the
bloodstream and become widely disseminated. Hemorrhagic and
necrotic lesions may develop in all organs.
Primary pneumonic plague
Results from inhalation of infective droplets (usually from a
coughing patient), with hemorrhagic consolidation of the lung,
sepsis and death.
Yersinia pestis
Clinical Diseases
Bubonic plague
Incubation period: 2-7 days.
High fever and painful lymphoadenopathy with greatly
enlarged, tender lymph nodes (buboes) in the groin and axilla
sepsis (early stage: vomiting and diarrhea; late stage:
hypotension, renal and cardiac failure; terminal stage:
pneumonia and meningitis). Mortality: 75% if untreated.
Pneumonic plague
Incubation time: 2-3 days.
Fever and malaise, pulmonary signs develop within 1 day.
Patients are highly infectious. Mortality: 90% if untreated.
Yersinia pestis
Treatment
Patients have to be promptly treated with antibiotics (drug of
choice: streptomycin).
Epidemiology and control
Plague is an infection of wild rodents that still occurs in many
parts of the world (enzootic areas: India, Southeast Asia, Africa,
and North and South America).
Control of plague requires surveys of infected animals, vectors,
and human contacts, and by destruction of infected animals.
All patients with suspected plague should be isolated.
Contacts of patients with suspected pneumonic plague should
receive tetracycline as chemoprophylaxis.
Y. enterocolitica and Y. pseudotuberculosis
Cause zoonotic infections.
Y. enterocolitica is a common cause of enteritis in cold areas
during the cold months. Y. pseudotuberculosis infection is
relatively uncommon.
They are found in the intestine of a variety of animals, and are
transmissible to humans through contaminated food, drink or
fomites, resulting in diarrhea, fever and abdominal pain that
last for 1-2 weeks or, in some cases, months. Most are selflimited.
Y. enterocolitica infection can cause pseudoappendicitis
(enlarged mesenteric lymph nodes) in children, and bloodtransfusion related sepsis in those who used blood products
stored for at least 4 weeks.
Y. enterocolitica grows slowly at 37 oC and prefers
cooler temperatures. The fecal specimen can be mixed
with saline and then store at 4 oC for 2 weeks or more
to facilitate isolation of this organism (cold enrichment).
How does
Proteus swarm?