Iron Deprivation by Oral Deferoxamine Application Alleviates Acute Campylobacteriosis in a Clinical Murine Campylobacter jejuni Infection Model

Abstract

The progressively rising food-borne Campylobacter jejuni infections pose serious health problems and socioeconomic burdens. Given that antibiotic therapy is not recommended for most campylobacteriosis patients, novel treatment options include strategies targeting iron homeostasis that impacts both C. jejuni virulence and inflammatory cell damage caused by toxic oxygen species. In our preclinical intervention study, we tested potential disease-alleviating effects upon prophylactic oral application of the iron-chelating compound desferoxamine (DESF) in acute murine campylobacteriosis. Therefore, microbiota-depleted IL-10-/- mice received synthetic DESF via the drinking water starting seven days before oral infection with C. jejuni strain 81-176. Results revealed that the DESF application did not reduce gastrointestinal pathogen loads but significantly improved the clinical outcome of infected mice at day 6 post-infection. This was accompanied by less pronounced colonic epithelial cell apoptosis, attenuated accumulation of neutrophils in the infected large intestines and abolished intestinal IFN-γ and even systemic MCP-1 secretion. In conclusion, our study highlights the applied murine campylobacteriosis model as suitable for investigating the role of iron in C. jejuni infection in vivo as demonstrated by the disease-alleviating effects of specific iron binding by oral DESF application in acute C. jejuni induced enterocolitis.

Disease alleviating effects following prophylactic lemon and coriander essential oil treatment in mice with acute campylobacteriosis

“…indicative of severe histopathology ( p < 0.001 versus naive; Figure 3A ; Supplementary Figure S1A ). Since apoptosis constitutes a reliable parameter for the grading of intestinal inflammatory morbidities including C. jejuni induced enteritis ( Bereswill et al, 2022 ), we applied quantitative in situ immunohistochemistry to count colonic epithelial cells that were positive for cleaved caspase-3. In fact, C. jejuni infection resulted in marked increases in apoptotic colonic epithelial cells ( p < 0.01–0.001 versus naive; Figure 3B ; Supplementary Figure S1B ).…”

Novel Iron Chelators, Super-Polyphenols, Show Antimicrobial Effects against Cariogenic Streptococcus mutans

“…In recent years, the use of iron chelators in the treatment of infectious diseases has been reported. Bereswill et al has reported recently that the disease-alleviating effects of specific iron binding by oral DFO application in the infection of Campylobacter jejuni induced acute enterocolitis in mouse models [27]. The antimicrobial and anti-biofilm activity of DFO against the oral bacteria Prevotella intermedia and P. gingivalis has also been reported [18,19].…”

Molecular Targets in Campylobacter Infections

“…Their respective mechanisms of action demonstrate that (i) LOS activity, (ii) pro-inflammatory mediators including oxygen radicals, (iii) intestinal barrier function and (iv) C. jejuni -related pathogenicity factors are well suited as molecular targets for the treatment and prevention of campylobacteriosis [ 157 , 179 , 180 ]. Finally, based on the key role of iron in ROS formation via the Fenton reaction, it was shown that iron deprivation by desferoxamine ameliorated murine campylobacteriosis [ 181 ]. In line with the inactivation of ROS by ascorbate (as mentioned above), these data showed that ROS production by innate immune cells represents another molecular target for treatment of human campylobacteriosis.…”