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Ami Febriza
Chronic Salmonella Infected
Mouse Model
Chronic Salmonella Infected
Mouse Model
 Animal experiments were performed by using specific-
pathogen-free female C57BL/6 mice that were 6-7 weeks old
 Each mouse will be given 7.5 mg of streptomycin
 At 20 hours after streptomycin treatment, withdrawn water
and food again before the mice are infected with bacteria
 1 x 106 to 10 x 108 colony-forming units, Salmonella was able
to colonize the mice
 Salmonella could be detected by fecal culture over 6 months
Animal Models for Salmonellosis:
Applications in Vaccine Research
Animal Models for Salmonellosis:
Applications in Vaccine Research
 Immunocompetent mouse models
 has been employed as the standard in the
Salmonella pathogenesis and vaccine
development
 There are two basic archetypes of systemic
infection mouse models for Salmonella. One
uses mice that are intrinsically susceptible to
Salmonella infections, and the other uses mice
that are resistant
 Susceptibility is best owed by mutations in genes that
are important for innate or acquired immunity to
intracellular pathogens. Contoh Nramp1-deficient
strains (Nramp1S; e.g., BALB/c,C57BL/6) → infection
via the oro gastric route leads to a systemic infection and
is ultimately lethal in several days or up to 2 weeks
(depending on the dose). These mice succumb following
parenteral infection with very low doses (< 10 CFU) of
highly virulent strains
 Resistent (Nramp1R) mice by using intraperitoneal or
intravenous infection with moderate bacterial doses
(e.g., 105 CFU), or via oral infection with very high
bacterial doses (e.g., 108 CFU).
Animal Models for Salmonellosis:
Applications in Vaccine Research
 Immunodeficient mouse models
 Used In Salmonella pathogenesis studies to investigate
the relative contributions of different elements of the
immune system to bacterial clearance
 these models have been used both to test the safety of
live attenuated vaccines and to determine the ability of
vaccines to elicit a response in immunodeficient hosts
 TLR11-deficient mice (tlr11-/-) → Knockout mice
infected perorally with 5 x 108 CFU of Salmonella Typhi
Ty2 developed a systemic illness similar to human
typhoid
Animal Models for Salmonellosis:
Applications in Vaccine Research
 Streptomycin mouse model
 Animals are pretreated with streptomycin to deplete the
normal flora prior to orogastric infection
 The depletion of the normal flora allows Salmonella to
colonize the cecum and colon,where it grows rapidly to
high density. Salmonella then invades the intestinal
mucosa, causing localized inflammation, before
spreading systemically
 Mice immunized orally with 2 x 107 CFU of attenuated
strain SA186 were shown to be protected from
homologous challenge with virulent Salmonella
Typhimurium post-streptomycin treatment
A mouse model for S.
typhimurium-induced enterocolitis
A mouse model for S.
typhimurium-induced enterocolitis
 Mouse model for S. typhimurium colitis : streptomycin
pretrestment revisited
 Recently, it was found that antibiotic pretreated mice
develop acute intestinal inflammation in response to
oral S. typhimurium infection: upon oral pretreatment
of mice with a single high dose of streptomycin (20 mg),
 S. typhimurium efficiently colonizes the large intestine
(108–1010 cfu per g) and triggers severe acute diffuse
inflammation of cecum and colon (colitis) as early as 8 h
post-infection
Effect of Streptomycin Administration
on Colonization Resistance to
Salmonella typhimurium in Mice
Effect of Streptomycin Administration on
Colonization Resistance to Salmonella
typhimurium in Mice
 When streptomycin-treated and untreated mice were
challenged orogastrically with 103 viable S.
typhimurium organisms, 100% of the treated and none
of the untreated mice excreted the pathogen in their
feces
 Translocation of S. typhimurium from the intestinal tract
to the liver, spleen, and mesentery occurred in 10 of 10
treated mice but in none of the untreated mice 7 days after
challenge with 103 CFU
 Studies showed that S. typhimurium was present at high
population levels in the intestines of streptomycin-
treated mice and in detectable levels in the liver, spleen,
and mesentery within 72 h after challenge with 103, 105,
or 108 organisms.
 In untreated mice challenged with either 103 or 105 S.
typhimurium organisms, the organisms were isolated
from ileal and cecal tissues but not from ileal or cecal
contents or from extraintestinal tissue 72 h after
challenge. When untreated mice were challenged with
108 organisms, however, S. typhimurium was present in
all organs and in intestinal contents.
 Streptomycin treatment, therefore, facilitated colonization
and development of streptomycin-resistant S.
typhimurium populations in intestines of mice and the
subsequent translocation of the organisms from the
intestinal tract to other tissues