scholarly journals Immune-modulatory Properties of the Octapeptide NAP in Campylobacter jejuni Infected Mice Suffering from Acute Enterocolitis

2020 ◽  
Vol 8 (6) ◽  
pp. 802 ◽  
Author(s):  
Markus M. Heimesaat ◽  
Soraya Mousavi ◽  
Sigri Kløve ◽  
Claudia Genger ◽  
Dennis Weschka ◽  
...  
Keyword(s):  
Immune Responses ◽  
Campylobacter Jejuni ◽  
Post Infection ◽  
Intestinal Tract ◽  
Clinical Signs ◽  
Global Public Health ◽  
Food Borne ◽  
Human Infections ◽  
First Time ◽  
Post Infectious

Human infections with the food-borne zoonotic pathogen Campylobacter jejuni are progressively rising and constitute serious global public health and socioeconomic burdens. Hence, application of compounds with disease-alleviating properties are required to combat campylobacteriosis and post-infectious sequelae. In our preclinical intervention study applying an acute C. jejuni induced enterocolitis model, we surveyed the anti-pathogenic and immune-modulatory effects of the octapeptide NAP which is well-known for its neuroprotective and anti-inflammatory properties. Therefore, secondary abiotic IL-10−/− mice were perorally infected with C. jejuni and intraperitoneally treated with synthetic NAP from day 2 until day 5 post-infection. NAP-treatment did not affect gastrointestinal C. jejuni colonization but could alleviate clinical signs of infection that was accompanied by less pronounced apoptosis of colonic epithelial cells and enhancement of cell regenerative measures on day 6 post-infection. Moreover, NAP-treatment resulted in less distinct innate and adaptive pro-inflammatory immune responses that were not restricted to the intestinal tract but could also be observed in extra-intestinal and even systemic compartments. NAP-treatment further resulted in less frequent translocation of viable pathogens from the intestinal tract to extra-intestinal including systemic tissue sites. For the first time, we here provide evidence that NAP application constitutes a promising option to combat acute campylobacteriosis.

scholarly journals Pituitary Adenylate Cyclase-Activating Polypeptide Alleviates Intestinal, Extra-Intestinal and Systemic Inflammatory Responses during Acute Campylobacter jejuni-induced Enterocolitis in Mice

Pathogens ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 805
Author(s):  
Markus M. Heimesaat ◽  
Soraya Mousavi ◽  
Sigri Kløve ◽  
Claudia Genger ◽  
Dennis Weschka ◽  
...  
Keyword(s):  
Adenylate Cyclase ◽  
Campylobacter Jejuni ◽  
Post Infection ◽  
Inflammatory Responses ◽  
Clinical Signs ◽  
Systemic Circulation ◽  
Cell Responses ◽  
Pituitary Adenylate Cyclase ◽  
Gastrointestinal Colonization ◽  
First Time

Human Campylobacter jejuni infections are emerging, and constitute a significant health burden worldwide. The ubiquitously expressed pituitary adenylate cyclase-activating polypeptide (PACAP) is well-known for its cell-protective and immunomodulatory effects. In our actual intervention study, we used an acute campylobacteriosis model and assessed the potential disease-alleviating effects of exogenous PACAP. Therefore, secondary abiotic IL-10−/− mice were perorally infected with C. jejuni and treated with synthetic PACAP38 intraperitoneally from day 2 until day 5 post-infection. Whereas PACAP did not interfere with the gastrointestinal colonization of the pathogen, mice from the PACAP group exhibited less severe clinical signs of C. jejuni-induced disease, as compared to mock controls, which were paralleled by alleviated apoptotic, but enhanced cell proliferative responses in colonic epithelia on day 6 post-infection. Furthermore, PACAP dampened the accumulation of macrophages and monocytes, but enhanced regulatory T cell responses in the colon, which were accompanied by less IFN-γ secretion in intestinal compartments in PACAP versus mock-treated mice. Remarkably, the inflammation-dampening properties of PACAP could also be observed in extra-intestinal organs, and strikingly, even the systemic circulation on day 6 post-infection. For the first time, we provide evidence that synthetic PACAP might be a promising candidate to combat acute campylobacteriosis and post-infectious sequelae.

scholarly journals Anti-Pathogenic and Immune-Modulatory Effects of Peroral Treatment with Cardamom Essential Oil in Acute Murine Campylobacteriosis

2021 ◽  
Vol 9 (1) ◽  
pp. 169
Author(s):  
Markus M. Heimesaat ◽  
Soraya Mousavi ◽  
Dennis Weschka ◽  
Stefan Bereswill
Keyword(s):  
Essential Oil ◽  
Post Infection ◽  
Intestinal Tract ◽  
Intervention Study ◽  
Inflammatory Mediator ◽  
Drug Resistant ◽  
Mediator Secretion ◽  
Intestinal Pathogen ◽  
Human Infections ◽  
Post Infectious

Human infections with enteropathogenic Campylobacter jejuni (C. jejuni) including multi-drug resistant isolates are emerging worldwide. Antibiotics-independent approaches in the combat of campylobacteriosis are therefore highly desirable. Since the health-beneficial including anti-inflammatory and anti-infectious properties of cardamom have been acknowledged for long, we here addressed potential anti-pathogenic and immune-modulatory effects of this natural compound during acute campylobacteriosis. For this purpose, microbiota-depleted IL-10−/− mice were orally infected with C. jejuni strain 81–176 and subjected to cardamom essential oil (EO) via the drinking water starting on day 2 post-infection. Cardamom EO treatment resulted in lower intestinal pathogen loads and improved clinical outcome of mice as early as day 3 post-infection. Furthermore, when compared to mock controls, cardamom EO treated mice displayed less distinct macroscopic and microscopic inflammatory sequelae on day 6 post-infection that were paralleled by lower colonic numbers of macrophages, monocytes, and T cells and diminished pro-inflammatory mediator secretion not only in the intestinal tract, but also in extra-intestinal and, remarkably, systemic organs. In conclusion, our preclinical intervention study provides the first evidence that cardamom EO comprises a promising compound for the combat of acute campylobacteriosis and presumably prevention of post-infectious morbidities.

scholarly journals Survey of Pathogen-Lowering and Immuno-Modulatory Effects Upon Treatment of Campylobacter coli-Infected Secondary Abiotic IL-10-/- Mice with the Probiotic Formulation Aviguard®

2021 ◽  
Vol 9 (6) ◽  
pp. 1127
Author(s):  
Dennis Weschka ◽  
Soraya Mousavi ◽  
Nina Biesemeier ◽  
Stefan Bereswill ◽  
Markus M. Heimesaat
Keyword(s):  
Immune Responses ◽  
Intestinal Tract ◽  
Clinical Signs ◽  
Campylobacter Coli ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Obligate Anaerobic ◽  
Intestinal Pathogen ◽  
Human Campylobacteriosis ◽  
Post Infectious

The prevalence of infections with the zoonotic enteritis pathogen Campylobacter coli is increasing. Probiotic formulations constitute promising antibiotic-independent approaches to reduce intestinal pathogen loads and modulate pathogen-induced immune responses in the infected human host, resulting in acute campylobacteriosis and post-infectious sequelae. Here, we address potential antipathogenic and immuno-modulatory effects of the commercial product Aviguard® during experimental campylobacteriosis. Secondary abiotic IL-10-/- mice were infected with a C. coli patient isolate on days 0 and 1, followed by oral Aviguard® treatment on days 2, 3 and 4. Until day 6 post-infection, Aviguard® treatment could lower the pathogen burdens within the proximal but not the distal intestinal tract. In contrast, the probiotic bacteria had sufficiently established in the intestines with lower fecal loads of obligate anaerobic species in C. coli-infected as compared to uninfected mice following Aviguard® treatment. Aviguard® application did not result in alleviated clinical signs, histopathological or apoptotic changes in the colon of infected IL-10-/- mice, whereas, however, Aviguard® treatment could dampen pathogen-induced innate and adaptive immune responses in the colon, accompanied by less distinct intestinal proinflammatory cytokine secretion. In conclusion, Aviguard® constitutes a promising probiotic compound to alleviate enteropathogen-induced proinflammatory immune responses during human campylobacteriosis.

scholarly journals Carvacrol ameliorates acute campylobacteriosis in a clinical murine infection model

Gut Pathogens ◽  
2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Soraya Mousavi ◽  
Anna-Maria Schmidt ◽  
Ulrike Escher ◽  
Sophie Kittler ◽  
Corinna Kehrenberg ◽  
...  
Keyword(s):  
Intestinal Tract ◽  
Farm Animals ◽  
Infection Model ◽  
Potential Candidate ◽  
Disease Symptoms ◽  
Ifn Γ ◽  
Human Infections ◽  
Candidate Molecule ◽  
Human Campylobacteriosis ◽  
Post Infectious

Abstract Background The prevalence of human infections with the zoonotic pathogen Campylobacter jejuni is rising worldwide. Therefore, the identification of compounds with potent anti-pathogenic and anti-inflammatory properties for future therapeutic and/or preventive application to combat campylobacteriosis is of importance for global health. Results of recent studies suggested carvacrol (4-isopropyl-2-methylphenol) as potential candidate molecule for the treatment of campylobacteriosis in humans and for the prevention of Campylobacter colonization in farm animals. Results To address this in a clinical murine infection model of acute campylobacteriosis, secondary abiotic IL-10−/− mice were subjected to synthetic carvacrol via the drinking water starting 4 days before peroral C. jejuni challenge. Whereas at day 6 post-infection placebo treated mice suffered from acute enterocolitis, mice from the carvacrol cohort not only harbored two log orders of magnitude lower pathogen loads in their intestines, but also displayed significantly reduced disease symptoms. Alleviated campylobacteriosis following carvacrol application was accompanied by less distinct intestinal apoptosis and pro-inflammatory immune responses as well as by higher numbers of proliferating colonic epithelial cells. Remarkably, the inflammation-ameliorating effects of carvacrol treatment were not restricted to the intestinal tract, but could also be observed in extra-intestinal organs such as liver, kidneys and lungs and, strikingly, systemically as indicated by lower IFN-γ, TNF, MCP-1 and IL-6 serum concentrations in carvacrol versus placebo treated mice. Furthermore, carvacrol treatment was associated with less frequent translocation of viable C. jejuni originating from the intestines to extra-intestinal compartments. Conclusion The lowered C. jejuni loads and alleviated symptoms observed in the here applied clinical murine model for human campylobacteriosis highlight the application of carvacrol as a promising novel option for both, the treatment of campylobacteriosis and hence, for prevention of post-infectious sequelae in humans, and for the reduction of C. jejuni colonization in the intestines of vertebrate lifestock animals.

scholarly journals Pilot experiment in chickens challenged with Campylobacter jejuni CCM6191 administered enterocin M-producing probiotic strain Enterococcus faecium CCM8558 to check its protective effect

2017 ◽  
Vol 62 (No. 11) ◽  
pp. 491-500 ◽  
Author(s):  
A. Laukova ◽  
M. Pogany Simonova ◽  
I. Kubasova ◽  
S. Gancarcikova ◽  
I. Placha ◽  
...  
Keyword(s):  
Campylobacter Jejuni ◽  
Post Infection ◽  
Enterococcus Faecium ◽  
Probiotic Strain ◽  
Ringer Solution ◽  
Culture Collection ◽  
Free Access ◽  
Food Borne ◽  
Enterocin M ◽  
Campylobacter Spp

Campylobacter jejuni is one of the most common food-borne pathogens and chickens are the main source of these bacteria. Enterococcus faecium AL41, enterocin M-producing strain (deponed to the Czech Culture Collection of Microorganisms, Brno, Czech Republic – CCM8558) is our isolate previously applied e.g. in broiler rabbits with beneficial effect. In this study it was used in a 11-day experiment with chickens (1-day-old, breed Cobb 500, n = 40) challenged with C. jejuni. Birds had free access to feed and water; they were randomly divided into four groups per 10 chicks each: control (CG), E. faecium CCM8558 (EG1), CCM8558 + C. jejuni CCM6191 (EG2), CCM6191 (EG3). E. faecium CCM8558 (10<sup>9 </sup>CFU/ml, 200 µl) in Ringer solution was administered daily per os to EG1 and EG2 for 7 days (from day 0–1). EG3 and EG2 were infected individually per os (day 4, CCM6191, 10<sup>8</sup> CFU/ml in Ringer solution, 200 µl). For microbiota evaluation, faecal mixtures (n = 5) were sampled on day 0–1 (1<sup>st</sup> sampling), on day 7 (2<sup>nd</sup> sampling), and on day 11 (3<sup>rd</sup> sampling) (day 7 of CCM8558 application, day 4 post-infection; day 4 of CCM8558 cessation, day 7 post-infection). Five birds from each group were sacrificed. CCM8558 sufficiently colonized chickens. In faeces of EG2 a tendency to reduce Campylobacter spp. (day 7 of application, day 4 of infection) was noted compared to EG2 (day 11, day 4 of cessation, day 7 post-infection; difference 1.21 log cycles), while in EG3 CCM6191 strain was not reduced. Phagocytic activity (PA) values were significantly higher in infected groups compared to CG and EG1. A significant increase in PA was also noted in EG2 and EG3 at the end of experiment compared to CG or EG1. The strain additive did not evoke oxidative stress. Biochemical parameters were influenced to the reference levels.

scholarly journals Increase in Acid Tolerance of Campylobacter jejuni through Coincubation with Amoebae

2010 ◽  
Vol 76 (13) ◽  
pp. 4194-4200 ◽  
Author(s):  
Diana Axelsson-Olsson ◽  
Lovisa Svensson ◽  
Jenny Olofsson ◽  
Paulo Salomon ◽  
Jonas Waldenström ◽  
...  
Keyword(s):  
Campylobacter Jejuni ◽  
Tap Water ◽  
Acid Tolerance ◽  
Poultry Production ◽  
Hygiene Practices ◽  
Food Borne ◽  
Gastrointestinal Pathogen ◽  
Human Infections ◽  
Phosphate Buffered Saline ◽  
Harsh Conditions

ABSTRACT Campylobacter jejuni is a recognized and common gastrointestinal pathogen in most parts of the world. Human infections are often food borne, and the bacterium is frequent among poultry and other food animals. However, much less is known about the epidemiology of C. jejuni in the environment and what mechanisms the bacterium depends on to tolerate low pH. The sensitive nature of C. jejuni stands in contrast to the fact that it is difficult to eradicate from poultry production, and even more contradictory is the fact that the bacterium is able to survive the acidic passage through the human stomach. Here we expand the knowledge on C. jejuni acid tolerance by looking at protozoa as a potential epidemiological pathway of infection. Our results showed that when C. jejuni cells were coincubated with Acanthamoeba polyphaga in acidified phosphate-buffered saline (PBS) or tap water, the bacteria could tolerate pHs far below those in their normal range, even surviving at pH 4 for 20 h and at pH 2 for 5 h. Interestingly, moderately acidic conditions (pH 4 and 5) were shown to trigger C. jejuni motility as well as to increase adhesion/internalization of bacteria into A. polyphaga. Taken together, the results suggest that protozoa may act as protective hosts against harsh conditions and might be a potential risk factor for C. jejuni infections. These findings may be important for our understanding of C. jejuni passage through the gastrointestinal tract and for hygiene practices used in poultry settings.

scholarly journals Disease-Alleviating Effects of Peroral Activated Charcoal Treatment in Acute Murine Campylobacteriosis

2021 ◽  
Vol 9 (7) ◽  
pp. 1424
Author(s):  
Stefan Bereswill ◽  
Soraya Mousavi ◽  
Dennis Weschka ◽  
Markus M. Heimesaat
Keyword(s):  
Immune Responses ◽  
Post Infection ◽  
Activated Charcoal ◽  
Treatment Options ◽  
Clinical Signs ◽  
Toxic Drug ◽  
Epithelial Cell Apoptosis ◽  
Intestinal Pathogen ◽  
Colonic Epithelial Cell Apoptosis ◽  
Antimicrobial Treatments

Foodborne Campylobacter jejuni infections are on the rise and responsible for worldwide serious health issues. Increasing resistance of C. jejuni strains against antimicrobial treatments, necessitates antibiotics-independent treatment options for acute campylobacteriosis. Activated charcoal (AC) constitutes a long-known and safe compound for the treatment of bacterial enteritis. In this preclinical intervention study, we addressed potential anti-pathogenic and immune-modulatory effects of AC during acute experimental campylobacteriosis. Therefore, microbiota-depleted IL-10−/− mice were infected with C. jejuni by gavage and challenged with either AC or placebo via the drinking water starting on day 2 post-infection. On day 6 post-infection, AC as compared to placebo-treated mice did not only harbor lower intestinal pathogen loads but also presented with alleviated C. jejuni-induced clinical signs such as diarrhea and wasting symptoms. The improved clinical outcome of AC-treated mice was accompanied by less colonic epithelial cell apoptosis and reduced pro-inflammatory immune responses in the intestinal tract. Notably, AC treatment did not only alleviate intestinal, but also extra-intestinal and systemic immune responses as indicated by dampened pro-inflammatory mediator secretion. Given the anti-pathogenic and immune-modulatory properties of AC in this study, a short-term application of this non-toxic drug constitutes a promising antibiotics-independent option for the treatment of human campylobacteriosis.

scholarly journals Antimicrobial susceptibility in thermophilic Campylobacter species isolated from pigs and chickens in South Africa

2010 ◽  
Vol 81 (4) ◽  
Author(s):  
A. Jonker ◽  
J.A. Picard
Keyword(s):  
Campylobacter Jejuni ◽  
Antimicrobial Susceptibility ◽  
Intestinal Tract ◽  
Inhibitory Concentration ◽  
Bacterial Disease ◽  
Western Cape ◽  
Oral Antibiotics ◽  
Food Borne ◽  
Thermophilic Campylobacter ◽  
Campylobacter Spp

Campylobacter jejuni is one of the leading causes of sporadic food-borne bacterial disease in humans. In intensive poultry and pig rearing systems the use of oral antibiotics is essential to maintain health. Consequently, there is a high risk for the thermophilic Campylobacter jejuni and C. coli resident in the intestinal tract of food animals to develop resistance to commonly used antibiotics. Contamination of meat or eggs with pathogenic strains of resistant Campylobacter could, therefore, result in a form of campylobacteriosis in humans that is difficult to treat. The aim of this investigation was to determine the antimicrobial susceptibility of thermophilic Campylobacter spp. isolated from pigs and poultry by the broth microdilution minimum inhibitory concentration (MIC) test. A total of 482 samples from the Western Cape and Gauteng provinces was collected and analysed. Thirty-eight Campylobacter isolates were obtained. Analysis of data revealed that C. jejuni strains mainly of poultry origin were more resistant to the fluoroquinolones, macrolides and tetracyclines and the C. coli strains were more resistant to the macrolides and lincosamides. Multiresistance was also detected in 4 Campylobacter strains from the Western Cape. With the exception of tetracyclines, strains from high health Gauteng broiler farms were susceptible to antibiotics used to treat Campylobacter infections.

scholarly journals Garlic Essential Oil as Promising Option for the Treatment of Acute Campylobacteriosis—Results from a Preclinical Placebo-Controlled Intervention Study

2021 ◽  
Vol 9 (6) ◽  
pp. 1140
Author(s):  
Markus M. Heimesaat ◽  
Soraya Mousavi ◽  
Dennis Weschka ◽  
Stefan Bereswill
Keyword(s):  
Essential Oil ◽  
Post Infection ◽  
Intervention Study ◽  
Immune Cell ◽  
Treatment Options ◽  
Clinical Signs ◽  
Antibiotic Resistant ◽  
Adjunct Treatment ◽  
Human Infections ◽  
Garlic Essential Oil

Since human infections with Campylobacter jejuni including antibiotic-resistant strains are rising worldwide, natural compounds might constitute promising antibiotics-independent treatment options for campylobacteriosis. Since the health-beneficial properties of garlic have been known for centuries, we here surveyed the antimicrobial and immune-modulatory effects of garlic essential oil (EO) in acute experimental campylobacteriosis. Therefore, secondary abiotic IL-10-/- mice were orally infected with C. jejuni strain 81-176 and garlic-EO treatment via the drinking water was initiated on day 2 post-infection. Mice from the garlic-EO group displayed less severe clinical signs of acute campylobacteriosis as compared to placebo counterparts that were associated with lower ileal C. jejuni burdens on day 6 post-infection. Furthermore, when compared to placebo application, garlic-EO treatment resulted in alleviated colonic epithelia cell apoptosis, in less pronounced C. jejuni induced immune cell responses in the large intestines, in dampened pro-inflammatory mediator secretion in intestinal and extra-intestinal compartments, and, finally, in less frequent translocation of viable pathogens from the intestines to distinct organs. Given its potent immune-modulatory and disease-alleviating effects as shown in our actual preclinical placebo-controlled intervention study, we conclude that garlic-EO may be considered as promising adjunct treatment option for acute campylobacteriosis in humans.

scholarly journals Treatment with the Probiotic Product Aviguard® Alleviates Inflammatory Responses during Campylobacter jejuni-Induced Acute Enterocolitis in Mice

2021 ◽  
Vol 22 (13) ◽  
pp. 6683
Author(s):  
Markus M. Heimesaat ◽  
Dennis Weschka ◽  
Soraya Mousavi ◽  
Stefan Bereswill
Keyword(s):  
Post Infection ◽  
Intestinal Tract ◽  
Inflammatory Responses ◽  
Apoptotic Cell ◽  
Feed Additives ◽  
Gastrointestinal Pathogen ◽  
Obligate Anaerobic ◽  
Probiotic Treatment ◽  
Probiotic Product ◽  
First Time

Prevalences of Campylobacter (C.) jejuni infections are progressively rising globally. Given that probiotic feed additives, such as the commercial product Aviguard®, have been shown to be effective in reducing enteropathogens, such as Salmonella, in vertebrates, including livestock, we assessed potential anti-pathogenic and immune-modulatory properties of Aviguard® during acute C. jejuni-induced murine enterocolitis. Therefore, microbiota-depleted IL-10−/− mice were infected with C. jejuni strain 81-176 by gavage and orally treated with Aviguard® or placebo from day 2 to 4 post-infection. The applied probiotic bacteria could be rescued from the intestinal tract of treated mice, but with lower obligate anaerobic bacterial counts in C. jejuni-infected as compared to non-infected mice. Whereas comparable gastrointestinal pathogen loads could be detected in both groups until day 6 post-infection, Aviguard® treatment resulted in improved clinical outcome and attenuated apoptotic cell responses in infected large intestines during acute campylobacteriosis. Furthermore, less distinct pro-inflammatory immune responses could be observed not only in the intestinal tract, but also in extra-intestinal compartments on day 6 post-infection. In conclusion, we show here for the first time that Aviguard® exerts potent disease-alleviating effects in acute C. jejuni-induced murine enterocolitis and might be a promising probiotic treatment option for severe campylobacteriosis in humans.

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