327 A humanized gnotobiotic piglet model to study host–microbiota interactions

2017 ◽  
Vol 95 (suppl_2) ◽  
pp. 159-159 ◽  
Author(s):  
N. D. Aluthge ◽  
W. Tom ◽  
T. E. Burkey ◽  
P. S. Miller ◽  
D. E. Hostetler ◽  
...  
Keyword(s):  
Gnotobiotic Piglet

scholarly journals Efficacy of Nitazoxanide againstCryptosporidium parvum in Cell Culture and in Animal Models

1998 ◽  
Vol 42 (8) ◽  
pp. 1959-1965 ◽  
Author(s):  
Cynthia M. Theodos ◽  
Jeffrey K. Griffiths ◽  
Jennifer D’Onfro ◽  
Alexandra Fairfield ◽  
Saul Tzipori
Keyword(s):  
Cell Culture ◽  
Clinical Trials ◽  
Body Weight ◽  
Animal Models ◽  
Cryptosporidium Parvum ◽  
Combined Treatment ◽  
Parasite Burden ◽  
Parasite Growth ◽  
Gnotobiotic Piglet

ABSTRACT Nitazoxanide (NTZ), a drug currently being tested in human clinical trials for efficacy against chronic cryptosporidiosis, was assessed in cell culture and in two animal models. The inhibitory activity of NTZ was compared with that of paromomycin (PRM), a drug that is partially effective against Cryptosporidium parvum. A concentration of 10 μg of NTZ/ml (32 μM) consistently reduced parasite growth in cell culture by more than 90% with little evidence of drug-associated cytotoxicity, in contrast to an 80% reduction produced by PRM at 2,000 μg/ml (3.2 mM). In contrast to its efficacy in vitro, NTZ at either 100 or 200 mg/kg of body weight/day for 10 days was ineffective at reducing the parasite burden in C. parvum-infected, anti-gamma-interferon-conditioned SCID mice. Combined treatment with NTZ and PRM was no more effective than treatment with PRM alone. Finally, NTZ was partially effective at reducing the parasite burden in a gnotobiotic piglet diarrhea model when given orally for 11 days at 250 mg/kg/day but not at 125 mg/kg/day. However, the higher dose of NTZ induced a drug-related diarrhea in piglets that might have influenced its therapeutic efficacy. As we have previously reported, PRM was effective at markedly reducing the parasite burden in piglets at a dosage of 500 mg/kg/day. Our results indicate that of all of the models tested, the piglet diarrhea model most closely mimics the partial response to NTZ treatment reported to occur in patients with chronic cryptosporidiosis.

scholarly journals Correction: Moxley, R.A., et al. Intimate Attachment of Escherichia coli O157:H7 to Urinary Bladder Epithelium in the Gnotobiotic Piglet Model. Microorganisms 2020, 8, 263

2020 ◽  
Vol 8 (12) ◽  
pp. 2016
Author(s):  
Rodney A. Moxley ◽  
Tom W. Bargar ◽  
Stephen D. Kachman ◽  
Diane R. Baker ◽  
David H. Francis
Keyword(s):  
Escherichia Coli ◽  
Urinary Bladder ◽  
Escherichia Coli O157 ◽  
Bladder Epithelium ◽  
Gnotobiotic Piglet

The authors wish to make the following corrections to this paper [...]

scholarly journals A Tripartite Fusion, FaeG-FedF-LT192A2:B, of Enterotoxigenic Escherichia coli (ETEC) Elicits Antibodies That Neutralize Cholera Toxin, Inhibit Adherence of K88 (F4) and F18 Fimbriae, and Protect Pigs against K88ac/Heat-Labile Toxin Infection

2011 ◽  
Vol 18 (10) ◽  
pp. 1593-1599 ◽  
Author(s):  
Xiaosai Ruan ◽  
Mei Liu ◽  
Thomas A. Casey ◽  
Weiping Zhang
Keyword(s):  
Escherichia Coli ◽  
Cholera Toxin ◽  
Enterotoxigenic Escherichia Coli ◽  
Content Type ◽  
Etec Strain ◽  
Severe Diarrhea ◽  
Heat Stable ◽  
Heat Labile ◽  
Young Pigs ◽  
Gnotobiotic Piglet

ABSTRACTEnterotoxigenicEscherichia coli(ETEC) strains expressing K88 (F4) or F18 fimbriae and heat-labile (LT) and/or heat-stable (ST) toxins are the major cause of diarrhea in young pigs. Effective vaccines inducing antiadhesin (anti-K88 and anti-F18) and antitoxin (anti-LT and anti-ST) immunity would provide broad protection to young pigs against ETEC. In this study, we genetically fused nucleotides coding for peptides from K88ac major subunit FaeG, F18 minor subunit FedF, and LT toxoid (LT192) A2 and B subunits for a tripartite adhesin-adhesin-toxoid fusion (FaeG-FedF-LT192A2:B). This fusion was used for immunizations in mice and pigs to assess the induction of antiadhesin and antitoxin antibodies. In addition, protection by the elicited antiadhesin and antitoxin antibodies against a porcine ETEC strain was evaluated in a gnotobiotic piglet challenge model. The data showed that this FaeG-FedF-LT192A2:B fusion elicited anti-K88, anti-F18, and anti-LT antibodies in immunized mice and pigs. In addition, the anti-porcine antibodies elicited neutralized cholera toxin and inhibited adherence against both K88 and F18 fimbriae. Moreover, immunized piglets were protected when challenged with ETEC strain 30302 (K88ac/LT/STb) and did not develop clinical disease. In contrast, all control nonvaccinated piglets developed severe diarrhea and dehydration after being challenged with the same ETEC strain. This study clearly demonstrated that this FaeG-FedF-LT192A2:B fusion antigen elicited antibodies that neutralized LT toxin and inhibited the adherence of K88 and F18 fimbrialE. colistrains and that this fusion could serve as an antigen for vaccines against porcine ETEC diarrhea. In addition, the adhesin-toxoid fusion approach used in this study may provide important information for developing effective vaccines against human ETEC diarrhea.

scholarly journals Studies with enteroaggregative Escherichia coli in the gnotobiotic piglet gastroenteritis model.

1992 ◽  
Vol 60 (12) ◽  
pp. 5302-5306 ◽  
Author(s):  
S Tzipori ◽  
J Montanaro ◽  
R M Robins-Browne ◽  
P Vial ◽  
R Gibson ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Gnotobiotic Piglet

scholarly journals Antimicrobial Therapies for Helicobacter pylori Infection in Gnotobiotic Piglets

1998 ◽  
Vol 42 (7) ◽  
pp. 1549-1554 ◽  
Author(s):  
Steven Krakowka ◽  
K. A. Eaton ◽  
Robert D. Leunk
Keyword(s):  
Helicobacter Pylori ◽  
Observation Interval ◽  
Dual Therapy ◽  
Immunoglobulin M ◽  
Therapy Regimen ◽  
Triple Therapy Regimen ◽  
Gnotobiotic Piglet ◽  
H Pylori ◽  
Gnotobiotic Piglets

ABSTRACT Gnotobiotic piglets infected with Helicobacter pyloriwere treated with various antimicrobials as monotherapy and dual therapy, and the results were compared to those for piglets treated with a triple-therapy regimen (bismuth subsalicyclate at 5.7 mg/kg of body weight, metronidazole at 4.4 mg/kg, and amoxicillin at 6.8 mg/kg four times a day [QID]). Clearance of infection was assessed after 7 days of treatment, and eradication was assessed following 7 days of treatment and a 14-day posttreatment observation interval. Monotherapy with amoxicillin, clarithromycin, and ciprofloxacin cleared and eradicated the organism from porcine stomachs; monotherapy with metronidazole cleared the infection and eradicated it from some piglets. Metronidazole-resistant microbes were recovered from treated piglets which cleared but did not eradicate the infection. Monotherapy with bismuth subsalicylate, erythromycin, nitrofurantoin, and tetracycline in the dosage range of 5.0 to 7.1 mg/kg QID was less than 100% effective in clearance and eradication, in that these drugs cleared and/or eradicated the infection from some of the piglets but did not eradicate the infection from all of the piglets. Monotherapy with an H-2 receptor antagonist (ranitidine) or a proton pump inhibitor (omeprazole) was ineffective at either clearance or eradication. In vivo dose titrations with several effective monotherapies were performed to determine the lowest effective in vivo dose of drug. In piglets, eradication was associated with a statistically significant decline in serum H. pylori-specific immunoglobulin M (IgM) antibodies; the titers of both IgA and IgG also declined, but the values were not statistically significant. For many antimicrobials, piglets are more sensitive indicators of clearance and eradication than humans. These data establish the H. pylori-infected gnotobiotic piglet as a useful model for the identification of novel antimicrobials for the treatment of this disease and for drug assessment during preclinical evaluations.

scholarly journals Colonization of Germ-Free Piglets with Mucinolytic and Non-Mucinolytic Bifidobacterium boum Strains Isolated from the Intestine of Wild Boar and Their Interference with Salmonella Typhimurium

2020 ◽  
Vol 8 (12) ◽  
pp. 2002
Author(s):  
Alla Splichalova ◽  
Radko Pechar ◽  
Jiri Killer ◽  
Zdislava Splichalova ◽  
Vera Neuzil Bunesova ◽  
...  
Keyword(s):  
Salmonella Typhimurium ◽  
Cell Count ◽  
Inflammatory Cytokines ◽  
Bacterial Translocation ◽  
Foodborne Pathogens ◽  
Clinical Signs ◽  
Germ Free ◽  
Tnf Α ◽  
Mucin 2 ◽  
Gnotobiotic Piglet

Non-typhoidal Salmonella serovars are worldwide spread foodborne pathogens that cause diarrhea in humans and animals. Colonization of gnotobiotic piglet intestine with porcine indigenous mucinolytic Bifidobacterium boum RP36 strain and non-mucinolytic strain RP37 and their interference with Salmonella Typhimurium infection were compared. Bacterial interferences and impact on the host were evaluated by clinical signs of salmonellosis, bacterial translocation, goblet cell count, mRNA expression of mucin 2, villin, claudin-1, claudin-2, and occludin in the ileum and colon, and plasmatic levels of inflammatory cytokines IL-8, TNF-α, and IL-10. Both bifidobacterial strains colonized the intestine comparably. Neither RP36 nor RP37 B. boum strains effectively suppressed signs of salmonellosis. Both B. boum strains suppressed the growth of S. Typhimurium in the ileum and colon. The mucinolytic RP36 strain increased the translocation of S. Typhimurium into the blood, liver, and spleen.

scholarly journals Intimate Attachment of Escherichia coli O157:H7 to Urinary Bladder Epithelium in the Gnotobiotic Piglet Model

2020 ◽  
Vol 8 (2) ◽  
pp. 263 ◽  
Author(s):  
Rodney A. Moxley ◽  
Tom W. Bargar ◽  
Stephen D. Kachman ◽  
Diane R. Baker ◽  
David H. Francis
Keyword(s):  
Escherichia Coli ◽  
Urinary Bladder ◽  
Enterohemorrhagic Escherichia Coli ◽  
Post Inoculation ◽  
Bladder Epithelium ◽  
Fecal Shedding ◽  
E Coli ◽  
Gnotobiotic Piglet ◽  
Immunohistochemical Evidence ◽  
Tract Infections

Enterohemorrhagic Escherichia coli (EHEC), a pathogenic subset of Shiga toxin-producing E. coli (STEC), is an important cause of hemorrhagic colitis and hemolytic–uremic syndrome (HUS), and a rare cause of urinary tract infections (UTIs) with associated HUS. EHEC strains attach intimately to intestinal epithelium with formation of actin pedestals (attaching-effacing (A/E) lesions); however, the mechanism of EHEC attachment to the uroepithelium is unknown. We conducted a retrospective study on archived urinary bladder specimens from gnotobiotic piglets that naturally developed cystitis associated with EHEC O157:H7 infection following oral inoculation and fecal shedding. Paraffin-embedded bladder tissues from three piglets with cystitis and immunohistochemical evidence of EHEC O157:H7 adherence to the uroepithelium were processed for and examined by transmission electron microscopy. EHEC O157:H7 bacteria were found in one of three piglets, intimately attached to pedestals on the apical surfaces of the superficial urothelium (umbrella cells). Cystitis was significantly associated with the length of survival of the piglets post-inoculation (p = 0.0339; estimated odds ratio = 2.6652). This is the first report of E. coli causing A/E-like lesions in the uroepithelium, and also evidence of the utility of the gnotobiotic piglet as a model for studies of the pathogenesis of EHEC UTIs.

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