Salmonella

salmonella gram stain

-ve

what are most salmonella cases associated with

contaminated food

what are the two classes of salmonella infections

typhoidal and non-typhoidal (based on the serovar responsible and the host immune response to the bacteria.

Description of typhoidal salmonella disease

disseminated infections with prolonged fever; headache, loss of appetite, and bradycardia

description of non-typhoidal salmonella disease

acute diarrhea, abdominal cramps, and fever; resolves in 1-7 days without treatment; compromised hosts may develop meningitis, osteomyelitis, etc.; more of a gastrointestinal infection

what do typhoidal serovars of salmonella cause

typhoid or paratyphoid fever

Example typhoidal salmonella serovars

S. typhi, S. paratyphi A, B and C, and S. sendai

how is typhoidal salmonella transmitted

highly adapted to humans and is mainly transmitted from an infected person or carrier (or sewage that was contaminated by an infected person)

What organisms can non-typhoidal salmonella infect?

humans and animals

how is non-typhoidal salmonella transmitted

from contaminated meat of chickens, pigs and cattleyes

is salmonella motile?

yes

What structure is involved in salmonella motility

flagella

What are several of the functions of the salmonella flagellum

1. motility

2. adherance

3. biofilm formation

4. avoid the immune system by phase variation

What are the two distinct flagella that Salmonella enterica can express

FliC and FljB

how do Salmonella enterica switch from expressing Flic to FljB?

antigenic variation. There is an upstream invertable DNA sequence with the promoter in it. There is a Hin site specific recombinase that forms a hairpin in the promoter region to mediate recombination and turn the promoter around. Now the promoter faces FliC instead of FljB and FljA (the repressor of FliC)

FGC

fimbrial gene cluster; on chromosome and plasmids

What types of fimbrae do salmonella encode

Type I fimbrae, Lpf, and PEF

Lpf

long polar fimbrae that mediates adherance to M cells and epithelial cells; phase variable to limit immune recognition

PEF

plasmid encoded fimbrae; lacks a tip adhesin; PefA binds Lewis blood group antigen and is involved in adhering to multiple cell lines

How does Salmonella infect host cells

1. bacteria adheres to M cell in the gut —> translocation

2. Enters macrophages

3. survival and growth in macrophages leads to local and systemic dissemination

4. released frem macrophage on basolateral side of gut cells

   1. inflammation

5. entry of the bact through the basolateral side of the epithelial cell

*There can also be direct invasion of epithelial cells

What does SPI stand for?

salmonella pathogenicity island

What are SPIs

virulence genes organized into clusters on chromosomes and are plasmids

What does the SPI-1 encode that is important for trigger invasion of non-phagocytic cells

T3SS

During SPI-1 mediated trigger invasion of non-epithelial cells, what effector proteins are involved

• SipA and SipC

• SopB, SopE, and SopE2

• SptP

SipA and SipC function

active during invasion; effectors that bind to actin, directly preventing its polymerization —> leads to the extension of pseudopods from the host cell

SopB, SopE, and SopE2 function

active during trigger mediated invasion; trigger Rac/Cdc42/RhoGTPases —> facilitate actin cytoskeleton remodeling via the ARP2/3 complex

What does SptP do after bacterial internalization

helps the host cytoskeleton recover so the bacteria have a nice host to exist inside of

what two invasion mechanisms does Salmonella use

Trigger and Zipper mechanisms

What mediates Salmonella Zipper invasion

• Rck

• PagN

How is Rck involved in zipper invasion

interacts with an epidermal growth factor receptor on host cell membrane → binding leads to phosphorylation of phosphoinositide-3-kinase → activates Rac1 and Cdc42 → leads to activation of the Arp2/3 complex and actin polymerization

How is PagN involved in salmonella zipper invasion

attaches to cell surface heparin sulfate proteoglycans → leads to phosphorylation of phosphoinositide-3-kinase → activates Akt kinase and Rac1 & Cdc42 —> leads to ARP2/3 complex and actin polymerization

Which SPI encodes the T3SS-1

SPI-1

Which SPI encodes the T3SS-2

SPI2

In a salmonella, what are T3SS-1 effectors important for?

early stages of SCV biogenesis

In a salmonella infection, what is the T3SS-2 involved in?

later steps of SCV maintenance; the effector proteins maintain SCV integrity by modifying the intracellular environment, position the SCV near the golgi, and aid in evading antibacterial strategies

how do invaded salmonella in the SCV avoid killing

SCVs do not fuse with lysosomal compartments

SseJ

Involved in est. of SCV: GCAT activity; modifies vacuole membrane composition to avoid lysosomal fusion; localizes the cytoplasmis side of SCV;

SifA

involved in establishment of SCV: salmonella infuced filament; SIF and SIST formation and microtubule interaction

How is the formation of the SCV damaging for the host?

T3SS-2 effectors that are translocated by the SCV induce apopsotis

SCV T3SS-2 effector proteins that are involved in apoptosis

• SpvB

• SseL

• SlrP

SpvB

T3SS-2 secreted ADP-ribosyltransferase toxin that promotes actin depolymerization and vacuolation

SseL

T3SS-2 secreted deubitquitinates proteins bound for degradation to limit cytotozicity and promote intracellular growth (after all, the bact. wants to promote some cell death in order to spread, but also it needs to keep its host environment for replication viable)

SlrP

ubiquitinates thioredoxin to promote degradation —> disrupts cellular homeostasis

what salmonella proteins promote NFKb degradation

GtagA, GogA, PipA

how is SpvC involved in modulating immune signaling?

dephosphorylates ERK/P38/MAPK to turn down pro inflammation

Why is the salmonela typhoid toxin an unusual AB toxin

possess two different A subunits

What the two different A subunits of the salmonella typhoid toxin

PltA and CDT

PltA function in salmonella typhoid toxin

ADP-ribosyltransferase covalently linked to CDT that facilitates toxin release from the bact.

What is the CDT function

nuclease that leads to G2/M cell cycle arrest —> cell death

How does typhoid toxin lead to the formation of rose spots?

homopentamer PltB binds to glycans on host cells → leads to emboli

have attempts been made to vaccinate against salmonella infections?

yes

Ty21a

live attenuated salmonella bacteria

ViCPS

capsule subunit vaccine derived from Ty21a

how are NTS usually treated?

antibiotics