Abstract
The World Health Organization has rated multidrug-resistant (MDR) Gram-negative bacteria including Pseudomonas aeruginosa (Psae) as serious threat to human health. We here addressed whether chronic murine gut inflammation facilitates intestinal MDR Psae colonization and whether bacterial infection subsequently worsens colonic immunopathology. Converse to wildtype counterparts, Psae colonized the intestines of IL-10−/− mice with chronic colitis following peroral challenge, but did not lead to changes in intestinal microbiota composition. Psae infection accelerated both macroscopic (i.e. clinical) and microscopic disease (i.e. colonic epithelial apoptosis), that were accompanied by increased intestinal pro-inflammatory immune responses as indicated by elevated colonic numbers of innate and adaptive immune cell subsets and enhanced secretion of pro-inflammatory cytokines such as TNF and IFN-γ in mesenteric lymph nodes of Psae-infected as compared to unchallenged IL-10−/− mice. Remarkably, Psae-induced pro-inflammatory immune responses were not restricted to the gut, but could also be observed systemically as indicated by increased TNF and IFN-γ concentrations in sera upon Psae-infection. Furthermore, viable commensals originating from the intestinal microbiota translocated to extra-intestinal compartments such as liver, kidney and spleen of Psae-infected IL-10−/− mice with chronic colitis only. Hence, peroral MDR Psae-infection results in exacerbated colonic as well as systemic pro-inflammatory immune responses during chronic murine colitis.
Highlights
Pseudomonas aeruginosa (Psae), constitute opportunistic pathogens, that may cause a variety of nosocomial infections in immunocompromised patients or patients with chronic pulmonary diseases such as chronic obstructive pulmonary disease or cystic fibrosis[1,2,3,4]
Mice with chronic colitis and healthy WT control animals were perorally infected with 109 colony-forming units (CFU) of a clinical MDR Psae strain
Both cultural and culture-independent analyses of fecal samples revealed that IL-10−/− mice with chronic colitis harbored comparable intestinal loads of the main intestinal bacterial groups before and 42 days after Psae challenge (Fig. 2)
Summary
Pseudomonas aeruginosa (Psae), constitute opportunistic pathogens, that may cause a variety of nosocomial infections in immunocompromised patients or patients with chronic pulmonary diseases such as chronic obstructive pulmonary disease or cystic fibrosis[1,2,3,4]. Our very recent study revealed for the first time that mere intestinal carriage of a clinical MDR Psae isolate by otherwise healthy microbiota-depleted wildtype (WT) mice resulted in distinct local as well as systemic pro-inflammatory immune responses[13]. We perorally challenged conventionally colonized IL-10−/− suffering from chronic colitis with a clinical MDR Psae isolate and assessed intestinal colonization properties of the opportunistic pathogen, shifts in gut microbiota composition, Psae-induced intestinal and systemic pro-inflammatory infectious sequelae, and translocation of viable bacteria to extra-intestinal including systemic compartments. Our data indicate that peroral MDR Psae infection exacerbates macroscopic and colonic apoptotic sequelae as well as systemic pro-inflammatory immune responses during chronic murine colitis
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