Med Bac - Salmonella

Who originally discovered Salmonella?

Theobald Smith

Who did Theobald Smith name Salmonella after?

His mentor Daniel Salmon

What was the original Salmonella species identified?

Salmonella choleraesuis

S. choleraesuis was later renamed to what?

Salmonella enterica

What disease is attributed to Salmonella?

Typhoid fever

What are the 3 species of Salmonella?

S. enterica, S. bongori, and S. subterranea

Which of the 3 Salmonella species are the only human pathogen?

S. enterica

Describe Salmonella enterica

Gram negative bacilli, mostly motile, facultative anaerobic

S. enterica is further divided into what classes based on antigen differences?

Serovars

What are the 4 major serovars of S. enterica?

Enteritidis, Typhi, Paratyphi, and Typhimurium

What are the 3 major antigens of S. enterica serovars?

Somatic (O antigen), Flagellar (H antigen), and Capsular (Vi antigen)

In S. enterica, what are the 2 phases of H antigen (flagellin)?

Phase 1 = FliC | Phase 2 = FljB

Phase variation of H antigen (FliC→FljB) requires what?

Genetic switch

In phase 1, FliC flagellin is produced but FljB is not due to what?

Inverted promoter

To switch to phase 2 and express FljB, what must occur?

Recombination of hix sites to invert the fljBP promoter

Once the promoter is inverted, what 2 proteins are expressed?

FljB and FljA

What is FljB?

Flagellin

What is FljA?

an sRNA repressor that inhibits translation of FliC

(T/F) Many non-typhoidal salmonella (NTS) serovars are zoonotic.

True

(T/F) Wild and domestic animal reservoirs exist for NTS, and transmission to humans is indirect usually from contaminated food.

True

What type of entry does Salmonella use?

Ingress

(T/F) Typhoidal S. enterica is also transmitted indirectly, and humans are the only known reservoir.

True

Typhoidal serovars of S. enterica are endemic to what regions of the world?

Southeast Asia and Africa

Asymptomatic carriage of typhoidal S. enterica occurs where?

Gall bladder, liver, spleen, and lymph nodes

(T/F) All S. enterica serovars can cause gastroenteritis, but only typhoidal S. enterica can cause typhoid fever.

True

What are the generic symptoms for NTS gastroenteritis?

Abdominal pain, nausea, diarrhea, vomiting

Although rare, what is the COD for NTS gastroenteritis?

Dehydration and hypovolemic shock

What are the symptoms of typhoid fever?

Disseminated rash, flu like symptoms, febrile, psychosis (confusion, muttering, delirium)

How does S. enterica invade enterocytes and what VF class does it use?

Enters via induction (forcing their way in) and uses invasins

What are the 2 types of induced cellular invasion?

Zipper and trigger

Describe zipper invasion.

Invasion is promoted from the outside by the interaction of an invasin with a host receptor (Yersinia and Listeria)

Describe trigger invasion.

Invasion is triggered internally by a secreted invasin (Salmonella and Shigella)

(T/F) Invasion involves host cytoskeletal rearrangement and vesicle formation.

True

VF for invasion by Salmonella are contained on what 2 genetic elements?

Salmonella pathogenicity islands (SPIs) and Salmonella virulence plasmid spvRABCD

What 2 VF are used by Salmonella for invasion?

SipA (Salmonella invasion protein) and T3S-1

Where are SipA and T3S-1 located?

On SPI-1

(T/F) The TS3-1 injects SipA into enterocytes for invasion.

True

Once inside an enterocyte (mediated by SipA and T3S-1) S. enterica can grow and replicate inside the phagosome and form what?

SCV (Salmonella containing vacuoles)

What SPI-encoded VF is used by Salmonella to survive in phagosomes and form SCVs?

SifA (Salmonella induced filaments)

What is SifA?

A G protein antagonist

How does SifA help S. enterica survive in SCVs?

SifA sequesters Rab9 → Rab9 is a G protein that mediates trafficking and delivery of antimicrobials to phagolysosomes

S. enterica can also detoxify ROS and RNS in the phagolysosome using what 2 VF?

KatE (catalase) and NirC (nitrite transporter)

Where are KatE and NirC encoded?

spvRABCD (Salmonella plasmid of virulence)

What SPI-encoded VF does S. enterica use to escape the SCV and continue replicating inside the cytoplasm?

SopB (Salmonella outer protein B)

What is SopB and what does it do?

SopB is a lipid phosphatase that ruptures the SCV membrane

What pore-forming toxin does S. enterica use to escape enterocytes and disseminate?

SipB (Salmonella invasion protein B)

What two S. enterica serovars produce typhoid toxin?

Typhi and Paratyphi

What classification is the typhoid toxin?

An AB class genotoxin

What are the 2 domains of the typhoid toxin?

Domain A = CdtB (cytolethal distending toxin → nuclease) | Domain B = PltB (pertussis-like toxin B → receptor binding domain)

How does the typhoid toxin work?

PltB (domain B) binds to Neu5Ac receptors and enters cells via receptor-mediated endocytosis → CdtB nuclease then travels to the nucleus and hydrolyzes DNA

What symptoms are used for presumptive diagnosis?

Fever, rose spotting, neuropathy, abdominal distension, tenderness

What are the 2 POCTs for typhoid?

Widal Test H-antigen and Typhidot OmpD

Culture on what plate is used for definitive ID of S. enterica?

XLD (xylose lysine deoxycholate agar)

S. enterica can ferment xylose on XLD and produces what as a byproduct that makes it appear black?

H2S

What PCR detection kit can be used for S. enterica?

iQ-check Salmonella II PCR Detection Kit

(T/F) There are no licensed vaccines for NTS, only for typhoid.

True

What is the live, attenuated oral vaccine for typhoid?

Vivotif

What is the injectable heat killed capsular vaccine for typhoid?

Typhim Vi

What is the main vaccine used that is a typhoid conjugate vaccine that uses the Vi capsule as the antigen?

Typbar TCV

(T/F) Antibiotic intervention is not usually needed for NTS, only supportive care, bedrest, and rehydration therapy.

True

What antibiotics are used for typhoid?

Azithromycin, ceftriaxone, and ciprofloxacin

Recently resistance to ciprofloxacin has risen due to a de novo target modification mutation in what gene?

gyrA (gyrase / topoII)