Salmonella

Theobald Smith

• known for work on texas cattle fever (babesiosis)

• isolated s. cholerasuis from pig, change to s. enterica

salmonella and history

typhoid made impact in jamestown, spanish-american war, civil war

two species of salmonella

s. enterica and s. bongori

serovars of s. enterica

* based on O (somatic), H (flagellar), and Vi (capsular) antigens

1. enteritidis (non-typhoidal)

2. typhi (typhoidal)

3. paratyphi (typhoidal)

4. typhimurium (non-typhoidal)

morphology and flagella

• gram (-), motile

s. enterica uses phase variation, which changes phases of flagella, to escape immune detection

1. FliC (phase 1) will be produced. FljB (phase 2) can’t be made since promoter is upsidedown

2. when it wants phase 2, recombination between hix sites will happen to invert FljB promoter

3. now FljB (flagella) and FljA (sRNA repressor) will be made. FljA binds to FliC mRNA to degrade it

chain of infection for non-typhoidal salmonellosis (NTS)

• all serovars can cause this

• can spread between sylvatic and domestic animal resevoirs

• humans get NTS by ingress (contaminated food)

chain of infection for typhoidal serovars of s. enterica

primary resevoir is humans

• infection through ingress (food/water) or direct contact

• typhoid is most commonly caused by serovar typhi

• carrier state for typhoidal serovar more common than for non-typhoidal serovar

salmonellosis

s. enterica will colonize small bowel as obligate pathogen

• can start as gastroenteritis and spread to typhoid fever

• health concern because many animal reservoirs and some can be infected but be asymptotic carriers of the obligate pathogen

  • carrier state of s. enterica can last for months to years and lead to less efficient transmission

describe NTS infection

1. s. enterica enteritidis invades intestine, causing barrier defects

2. NTS is triggered. get symptoms like nausea, vomiting, diarrhea

3. patient get better in 10 days 

how does s. enterica typhi enter and leave phagocytic cell

1. s. enterica needs to invade tissue (induced, transcytosis, phagocytosis)

* uses virulence factors from salmonella pathogenicity island (SPI) and spvRABCD (plasmid)

2. T3S-1 will secret SipA, triggering phagocytosis through Arp2/3 using host actin

3. s. enterica will replicate in phagosome, turning it into salmonella containing vacuole (SCVs)

4. It will use T3S-2 to secret Sif-A, which sequesters Rab 9. 

* Rab 9 used to deliver AMP to phagolysosome. without this, the phagolysosome forms, but s. enterica can survive in the vacuole 

5. the plasmid encodes NirC, used to protect SCV from nitrostative stress, and KatE, used to protect SCV from oxidative stress

6. s. enterica will use T3S-1 to secret SipB which activates caspase-1 for apoptosis so that it can disseminate

describe typhoid fever

• what happens when gastroenteritis disseminates

• symptoms: rose spots, swollen stomach, fever, confusion

• gastroenteritis → typhoid fever → septic shock and intestinal perforation

  • septic shock and intestinal perforation are LPS and typhoid toxin-mediated

typhoid A2B5 toxin

* genotoxin

1. toxin from typhi and paratyphi serovars binds to sialic acid receptors (PltB -receptor binding b domain) in URT, GIT, or CNS

2. will be vacuolized through receptor-mediate endocytosis

3. trafficked to nucleus, on the way there, PltA (CdtB delivery subunit) dissociates from CdtB (nuclease toxin)

4. in the nucleus, CdtB creates lesions in DNA and induces cytotoxicity by apoptosis. leads to perforation in GIT or neuropathy in CNS

presumptive diagnosis and POCT

all serovars

• gastroenteritis, neuropathy

typhi and paratyphi

• abdominal distension, rose spots

POCT

• widal test, typhidot

definitive diagnosis

gram stain

• differential stain: salmonella (-/ pink)

XLD

• differential: test whether can ferment xylose and produce H2S end product - salmonella (+/black) vs e.coli (-/white)

• IQ-check salmonella II PCR detection kit

differential diagnosis

gastroenteritis

• e.coli or shigella

neuroapthy

• diabetes or rheumatoid arthritis

prevention and treatment

animals

• reduce shedding of salmonella in livestock and poultry

• reduce contamination during processing of animal carcass

typhoid vaccines

• vivotiff: pill, attenuated for high risk

• typhim vi: heat-killed polysaccharide vaccine

typhoid antibiotics

• azithromycin and ceftriaxone

* no vaccine or antibiotic for NTS, just rehydrate