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  • Author or Editor: W. Markus x
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Abstract

The widespread misuse of antibiotics leads to a rapid development of multi-drug resistant (MDR) bacterial pathogens all over the globe, resulting in serious difficulties when treating infectious diseases. Possible solutions are not limited to the development of novel synthetic antibiotics but extend to application of plant-derived products either alone or in combination with common antibiotics. The aim of this actual review was to survey the literature from the past 10 years regarding the antibacterial effects of distinct Artemisia species including Artemisia absinthiae constituting an integral component of the Absinthe drink. We further explored the synergistic antibacterial effects of the Artemisia plant products with established antibiotics. The survey portrays the Artemisia derived compounds as potent antibacterial agents that can even restore the efficacy of antibiotics against MDR bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA) and MDR Escherichia coli. This, in turn, is presumably triggered in part by the interaction of the Artemisia ingredients with the efflux pumps of MDR bacteria. In conclusion, biologically active molecules in Artemisia plants enhance the antibiotic susceptibility of resistant bacteria, which provide promising future therapeutic strategies to combat MDR bacterial pathogens.

Open access

Abstract

Secondary abiotic (SAB) IL-10−/− mice constitute a valuable Campylobacter jejuni-induced enterocolitis model. Given that the host-specific gut microbiota plays a key role in susceptibility of the vertebrate host towards or resistance against enteropathogenic infection, we surveyed immunopathological sequelae of C. jejuni infection in human microbiota associated (hma) and SAB IL-10−/− mice. Following oral challenge, C. jejuni readily colonized the gastrointestinal tract of hma and SAB mice, but with lower numbers in the former versus the latter. Whereas hma mice were clinically less severely compromised, both, macroscopic and microscopic inflammatory sequelae of C. jejuni infection including histopathological and apoptotic cell responses in the colon of IL-10−/− mice were comparably pronounced in the presence and absence of a human gut microbiota at day 6 post-infection. Furthermore, C. jejuni infection of hma and SAB mice resulted in similarly enhanced immune cell responses in the colon and in differential pro-inflammatory mediator secretion in the intestinal tract, which also held true for extra-intestinal including systemic compartments. Notably, C. jeuni infection of hma mice was associated with distinct gut microbiota shifts. In conclusion, hma IL-10−/− mice represent a reliable C. jejuni-induced enterocolitis model to dissect the interactions of the enteropathogen, vertebrate host immunity and human gut microbiota.

Open access

Abstract

Background

Acute campylobacteriosis caused by oral infections with the enteropathogen Campylobacter jejuni represent serious threats to global human health. Since novel treatment options with safe and antibiotics-independent compounds would be highly appreciable, we here investigated the anti-bacterial and disease-alleviating effects of carvacrol, butyrate, ellagic acid, and 2′-fucosyl-lactose in acute murine campylobacteriosis. To address this, secondary abiotic IL-10−/− mice were perorally infected with C. jejuni and treated with either compound alone or all four in combination via the drinking water starting two days post-infection.

Results

On day 6, the duodenal pathogen loads were lower in mice of the combination versus the vehicle treatment cohort. Importantly, mice treated with carvacrol and the combination presented with less distinct diarrheal symptoms, colonic histopathology, epithelial cell apoptosis, and immune cell responses when compared to vehicle counterparts on day 6 post-infection. Furthermore, the combination treatment did not only diminish colonic IFN-γ, TNF-α, and IL-6 secretion in C. jejuni infected mice, but also dampened extra-intestinal and even systemic pro-inflammatory cytokine concentrations to basal levels as measured in liver, kidneys, lungs, and serum samples.

Conclusions

Our preclinical placebo-controlled intervention trial provides evidence that the combined oral application of carvacrol, butyrate, ellagic acid, and 2′-fucosyl-lactose alleviates acute campylobacteriosis in the vertebrate host.

Open access

Abstract

Human infections with the food-borne zoonotic enteropathogen Campylobacter jejuni are increasing globally. Since multi-drug resistant bacterial strains are further on the rise, antibiotic-independent measures are needed to fight campylobacteriosis. Given its anti-microbial and anti-inflammatory properties the polyphenolic compound resveratrol constitutes such a promising candidate molecule. In our present placebo-controlled intervention trial, synthetic resveratrol was applied perorally to human gut microbiota-associated (hma) IL-10−/− mice starting a week before oral C. jejuni infection. Our analyses revealed that the resveratrol prophylaxis did not interfere with the establishment of C. jejuni within the murine gastrointestinal tract on day 6 post-infection, but alleviated clinical signs of campylobacteriosis and resulted in less distinct colonic epithelial apoptosis. Furthermore, oral resveratrol dampened C. jejuni-induced colonic T and B cell responses as well as intestinal secretion of pro-inflammatory mediators including nitric oxide, IL-6, TNF-α, and IFN-γ to basal levels. Moreover, resveratrol application was not accompanied by significant shifts in the colonic commensal microbiota composition during campylobacteriosis in hma IL-10−/− mice. In conclusion, our placebo-controlled intervention study provides evidence that prophylactic oral application of resveratrol constitutes a promising strategy to alleviate acute campylobacteriosis and in consequence, to reduce the risk for post-infectious autoimmune sequelae.

Open access