Lecture 27: Salmonella and Shigella

Salmonella, Shigella, and Escherichia coli Overview

Enterobacteriaceae → bacteria of the intestine

Gram-negative rods (bacilli)

Cell Envelope:

Inner and outer membrane

Flagella (H antigen)

Capsule (K or Vi)

LPS (O antigen)

Peptidoglycan

Most are motile with peritrichous flagella

Non-motile species include: Yersinia, Klebsiella, Shigella

Fimbriae/Pili

Common pili – chromosomally encoded, aid in host cell attachment

Sex or conjugative pili – horizontal gene transfer

Salmonella, Shigella, and Escherichia coli Virulence Factors

Endotoxin:

Lipid A component of LPS

In blood stream, can lead to septic shock

Capsule:

Some, not all Enterobacteriaceae have

Protects from phagocytosis, complement

T3SS – Type Three Secretion Systems:

Widely used by gram -ve, often have multiple systems within same strain

Injects bacterial proteins into host cells to manipulate the cellular processes

Salmonella Species

Facultative anaerobe

Two species:

Salmonella bongori

Salmonella enterica: Cause most human infections

Salmonella enterica serovar Typhi

Salmonella enterica Overview

Most isolates are motile with peritrichous flagella

Foodborne gastroenteritis

Modes of transmission:

Primary sources:

Ingestion of contaminated food or water

Eggs, poultry

Organic vegetables

Meat and dairy

Secondary sources

Pet reptiles or birds

Backyard poultry flocks

Direct person to person transmission

Two Salmonella enterica serovars cause most human gastroenteritis

Salmonella enterica serovar Typhimurium: Causes self-limiting gastroenteritis in humans

Salmonella enterica serovar Enteritidis:

Non-typhoidal Salmonella (NTS)

Clinically, diseases present as indistinguishable

Salmonella enterica Pathogenesis

Bacteria attach to the intestinal epithelial cells

Inserts bacterial proteins into cells to induce phagocytosis

Flagellins and LPS are recognized by pattern recognition receptors such as TLRs

Bacteria reproduce in the phagocytic vesicles and cause cell death

Prevents the fusion of the phagosome with the lysosome

Invasion of epithelial cells stimulates the release of proinflammatory cytokines which induce an inflammatory reaction

They then transit the epithelial layer, gaining access to systemic sites

Invasion of the intestinal mucosa is followed by activation of mucosal adenylate cyclase (mechanism unknown); the resultant increase in cyclic AMP induces secretion of water

Diarrhea is due to secretion of fluid and electrolytes by the small and large intestines

Stool may contain polymorphonuclear leukocytes, blood, and mucus

Acute inflammatory response causes ulceration

Bacteria migrate into mesenteric lymph nodes

Salmonellosis

Incubation period up to 7 days

Nausea, headache, vomiting, profuse diarrhea (sometimes bloody)

Low-grade fever, abdominal cramps are common

Inflammatory lesions of small and large intestines

Diarrhea is usually self-limited, duration is 3-7 days

Complications:

Bacteremia

Meningitis: Inflammation of the meninges

Septic arthritis

Osteomyelitis

Aneurysms

Salmonella enterica Diagnosis

Isolation of bacteria from stool samples

Grown on MacConkey agar with lactose

Salmonella are non-lactose fermenter and therefore produces colorless colonies on MacConkey agar

Produce H2S on Salmonella-Shigella (SS) agar

Produces colorless colonies with a black center on SS agar

Allows differentiation between Salmonella and Shigella

Septic patients:

Blood and urine specimens

Test for antigens

Agglutination test

Tube dilution test

PCR

Salmonella enterica Treatment

Non-typhoidal gastroenteritis:

Self-limiting for otherwise healthy patients

Fluids to treat for dehydration

Treatment with antibiotics is discouraged

Can prolong gastrointestinal symptoms

Contributes to the spread of antibiotic resistance

Immunocompromised patients, neonates, patients older than 50 and with confirmed atherosclerosis, cardiac valvular or endovascular disease should be treated with antibiotics alongside fluids:

Ciprofloxacin, trimethoprim-sulfamethoxazole, ampicillin, or third generation cephalosporins

Probiotics

Shigella Overview

Gram-negative rods (bacillus)

Facultative anaerobic, non-spore-forming bacteria

Nonmotile, non-lactose-fermenting

Four species:

S. dysenteriae – most virulent

S. flexneri

S. boydii

S. sonnei

Fecal – oral route

Humans are the sole reservoir

Transmitted by “Food, fingers, feces, and flies” from person to person

Highly infectious organism

Highest incidence in children of 1-4 yrs. of age

High-risk groups:

Immunocompromised status

Childcare settings, adult care homes, shelters

International travel to areas with poor sanitation can increase exposure

Shigella Toxins

S. dysenteriae produces an enterotoxin called Shiga toxin (1 and 2): One of the most potent biological poisons known

A-B toxin:

Binds to a glycolipid receptor on host cells called globotriaosylceramide (Gb3)

Inhibits host protein synthesis causing cell death

Results in damage in intestinal lining causing fluid loss an bloody diarrhea

Shigella enterotoxins (ShET)

ShET-1:

Produced by Shigella flexneri

Chromosomally encoded

Increase fluid secretion in the intestines

ShET-2:

Produced by different Shigella species, including S. flexneri, S. sonnei, and S. dysenteriae

Plasmid encoded

Contribute to the watery diarrhea

Shigella Pathogenesis

Infection begins with the ingestion of the bacteria

Shigella bacilli invade mucosal epithelial cells (M cells)

Bacteria escape from phagocytic vacuole

Spread from cell to cell by actin polymerization on one end

Cell damage results in microabscesses in the large intestinal wall

Results in fluid loss, ulceration, bleeding

Shigellosis

Bacilli Invade and multiply in colon epithelial cells

Incubation period is 1-4 days

Sudden onset of fever, abdominal cramp

Followed by diarrhea

Initial feature is watery diarrhea associated with toxin

In 1- 2 days, number of stools increases, and bowel movement is accompanied by rectal spasms (tenesmus)

Can range from watery diarrhea to severe bloody diarrhea with mucus in stool (dysentery)

Infection limited to GI tract, bloodstream infections are rare

Water and electrolyte loss may lead to dehydration, acidosis, and death

Shigellosis Complications

Bloodstream infections

Post-infectious Arthritis (Reactive Arthritis): Autoimmune condition that can develop weeks to months after the initial Shigella infection, particularly with the Shigella flexneri species

Hemolytic-Uremic Syndrome (HUS): Red blood cells are destroyed; associated with Shigella dysenteriae

Neurological Complications: More common in children

They are often linked to high fever: Febrile seizures, encephalopathy (confusion, lethargy, coma)

Shigella Diagnosis

Diagnosis based on symptoms and presence of Shigella in stool

Culture:

Colorless colonies on Salmonella-Shigella (SS) agar

Non-lactose fermenter – colorless colonies on MacConkey agar

xTAG pathogen panel can be used to detect Shigella

PCR can be used

Shigella Treatment

Usually, self-limiting

Supportive care

Fluid replacement

Antibiotics may prolong signs of infection

Effective antibiotic therapy may be required for severe cases

Widespread resistance against Trimethoprim-sulfamethoxazole and ampicillin in the US

Ciprofloxacin, ceftriaxone, azithromycin can be used based on resistance profile

Some strains are extremely drug resistant (XDR)