49. Salmonella and Shigella

Question 1

what is the real species of S.typhinurium?

Answer 1

Salmonella enterica, subspecies enterica, serovar Typhinurium

Question 2

typhoid vs NTS disease?

Answer 2

• Typhoid: systemic syndrome, enteric fever (life threatening
• NTS: diarrhea (inflammatory)

Question 3

Typhoid vs NTS - which can you treat w/Abx? which has vaccines?

Answer 3

Typhoid for both

Question 4

NTS epidemiology?

Answer 4

• infections assoc w/poultry eggs, and dairy
• raw meat, fruits, veggies
• contaminated prep area
• animal hosts
• infectious dose is low
• self-limiting infections
• carried asymptomatically by lots of vertebrate species
• some NTS in kids

Question 5

NTS disease?

Answer 5

• gastroenteritis (“inflammatory enteritis”)
• watery diarrhea: blood, pus, and mucous
• abd pain, fever
• immunocompromised hosts: bacteremia and systemic suppurative foci (bone, lung, meninges, etc)

Question 6

NTS tx?

Answer 6

• antidiarrheals

- NO ABX

Question 7

Typhoid Salmonella Epi?

Answer 7

• adapted to cause disease in humans only
• world health problem
• ingestion of contaminated food/water
• asymptomatic excretion from gallbladder colonization chronic carriers (gallstones and bile induced biofilm formation may be impt)

Question 8

Typhoid salmonella disease?

Answer 8

• “typhoid fever” = enteric fever
• generalized systemic infection of the reticuloendothelial system
• No diarrhea
• 5-21 days inc period
• malaise, headache, cough, sore throat, constipation, muscle aches, CNS abnormalities
• febrile and ill-appearing
• rose spots, hepatosplenomegaly, abdominal tenderness
• 10-30% mortality untreated (1% treated)
• can lead to pna, meningitis, or intestinal perforation (intestinal hemorrhage is the most common cause of death)

Question 9

typhoid salmonella tx and vaccine?

Answer 9

• remember to think of typhoid fever in febrile pts who have traveled to developing areas as problem when undiagnosed early
• FQ (ciprofloxacin)
• S.enterica MDR to many first line Abx (ie ampicillin, chloramphenicol, TMP-SMX)
• live attenuated oral vaccine (Ty21a)
• Vi capsular polysaccharide (parenteral)
• no vaccine for pts

Question 10

salmonella pathogenesis?

Answer 10

• all salmonella are invasive (mucosal invasion)
• bacterium adheres to small bowel mucosa
• via T3SS, internalized into M cells and enterocytes (cell membrane disrupted transiently to engulf organism, has effects on actin dynamics causing cytoskel alterations)
• 2nd T3SS to prevent lysosomal fusion – multiplies w/in vacuole
• bacteria escape and infect others
• cause inflammation: Typhoidal involves minimal inflammation and neutrophil transmigration w/restrained immune response while NTS causes significant inflammation and neutrophil recruitment which may contain the infection
• inflammation re: T3SS-1 creating inflammasome, LPS binding TLR4, and Flagella binding TLR5
• *Inflammation induced by salmonella confers competitive advantage in the intestine:
• host releases antimicrobial peptide lipocalin-2
• lipocalin binds enterobactin (siderophore produced by enteric bacteria)
• salmonella produces salmchelin that is not bound by lipocalin
• thus salmonella has an advantage over other gut microbes (gets the iron it wants)
• also use of tetrathionate for respiration

Question 11

salmonella virulence?

Answer 11

• T3SS encoded on PAIs (pathogenicity islands)
• regulators
• adherence fimbriae
• salmochelin expression - tetrathionate utilization (NTS only)

S.typhi only:

• Vi antigen: capsule that reduces inflammatory response by evading TLR4
• altered flagellin gene regulation evades TLR5
• genome degradation

Question 12

Shigella microbiology?

Answer 12

• GNR
• non-motile
• closely related to EIEC
• enterobacteriaceae

Question 13

most common shigella in US?

Answer 13

S.sonnei - traveler’s diarrhea

Question 14

most common shigella in the world?

Answer 14

S. flexneri - traveler’s diarrhea

Question 15

most severe shigella?

Answer 15

S. dysenteriae

• Most severe – more virulent and infectious
• explosive outbreaks and epidemics
• all age groups
• high attack rates

Question 16

shigella epidemiology?

Answer 16

• humans are only reservoir
• not usu chronic carriers
• person-person spread
• low inoculum thus institutional outbreaks

Question 17

shigella virulence?

Answer 17

Virulence plasmid:

• T3SS (invasion)
• effectors
• enterotoxins

Avl = antivirulence locus that is lost

S. dysenteriae has shiga toxin that leaves 28S rRNA

Question 18

shigella disease?

Answer 18

• dysentery (freq small volume stools w/blood & mucus)
• strains at the stool (tenesmus)
• inflammatory diarrhea w/cramps, fever, malaise
• Complications: colitis (can cause hemorrhage), persistent diarrhea and dehydration, protein loss, malnutrition and cognitive defects, rectal prolapse, intestinal perforation and bacteremia are rare
• can lead to reactive arthritis (Reiter’s syndrome) (arthritis, urethritis, conjunctivitis – autoimmune)

S. dysenteriae: - Severe colitis

• neurologic complications
• HUS
• high mortality

Question 19

shigella dx and tx?

Answer 19

• blood, pus, and heavy mucus in the stool
• Abx is usually effective (unlike salmonella diarrhea)
• TMP/SMX most commonly used
• watch for complications
• maintain hydration
• pay attention to epidemiology
• no vaccine

S.dysenteriae has MDR strains!