Marine prebiotics mediate decolonization of Pseudomonas aeruginosa from gut by inhibiting secreted virulence factor interactions with mucins and enriching Bacteroides population

Abstract

Background Pseudomonas aeruginosa intestinal carriage rates are significantly higher in immunosuppressed individuals and hospitalized patients who therefore have increased risk of infections and antibiotic-associated diarrhea. To combat intestinal dysbiosis and decolonize P. aeruginosa from gastrointestinal tract, we investigated the anti-adherence and gut microbiota modulation properties of marine prebiotic fucoidans. Methods Proteomic analysis of culture supernatant was performed by LC–MS/MS. Using lectin-based enzyme-linked immunosorbent assay, hemagglutinin domain interaction and inhibition with biomolecules were studied. We investigated the role of nutritional grade fucoidans in a mouse model and used 16S ribosomal RNA sequencing to examine fecal microbiota composition. Results Analysis of culture supernatant proteins indicated the secretion of two-partner secretion (TPS) family proteins, including TpsA1/CdiA2 and TpsA2/CdiA1. Lectin like activity at the N-terminal of TpsA due to a conserved hemagglutinin domain (Pfam identifier [ID] PF05860) mediates binding to mucins that carry multiple fucosylated glycans. Fucose-rich sulfated polysaccharides (fucoidans) and sulfated dextrans were found to be potent inhibitors of the recombinant N-terminal hemagglutinin domain of TpsA (TpsA-NT-HAD) binding to mucins. In a mouse model, antibiotic-induced dysbiosis was essential for P. aeruginosa gastrointestinal colonization. After prophylactic oral fucoidans supplementation, a higher proportion (60%) of the mice were decolonized over time and resisted re-colonization, this was associated with remarkable expansion of Bacteroides (post-infection day-3 abundance, 29–50%) and consequential reductions in bloom of Enterobacteriaceae and Enterococcaceae populations. In the non-supplemented group, Parabacteroides mediated recovery from dysbiosis but failed to decolonize P. aeruginosa. Conclusions Supplementing diet with marine prebiotic fucoidans can mediate earlier recovery from dysbiosis and decolonization of P. aeruginosa from gut by inhibiting secreted virulence factor (TpsA/CdiA) interaction with mucins and promoting the growth of beneficial Bacteroides population. We suggest the prophylactic use of nutritional grade fucoidans to decolonize P. aeruginosa from gastrointestinal tract of at-risk individuals to prevent infection and transmission of colonizing P. aeruginosa.

Red pandas with different diets and environments exhibit different gut microbial functional composition and capacity

“…Pseudomonas, although a common opportunistic pathogen, is not readily able to infect the gut (Chuang et al 2017). Species such as Pseudomonas aeruginosa are more often associated with lung infections and with enterocolitis in children (Hoff et al 2020;Janapatla et al 2023). Bamboo shoots, while nutrient rich and protein dense, may initiate an increase in pathogenic microorganisms due to their high and undigested protein content, potentially elevating the risk of metabolic diseases (Zhao et al 2019).…”

“…2020; Janapatla et al. 2023). Bamboo shoots, while nutrient rich and protein dense, may initiate an increase in pathogenic microorganisms due to their high and undigested protein content, potentially elevating the risk of metabolic diseases (Zhao et al.…”

Host microRNA interactions with the SARS-CoV-2 viral genome 3’-untranslated region

“…The normalized intensity was recorded and fitted to equation 2 for determination of the IC50 value (AAT Frye 12 Bioquest, equation adapted in Origin Pro) for the experiment. (48)(49)(50)(51)(52) In equation 2, F max and F min represent the maximum and minimum fluorescent intensities of the experiment. F o represents the fluorescent intensity at each data point, and [S] o represents the concentration of competing ligand, in this case the FANAs or untagged miRs.…”

Therapeutic Approach Targeting Gut Microbiome in Gastrointestinal Infectious Diseases

“…There have been successful examples of using probiotics and FMT to treat its infection in humans [163,164]. Janapatla et al reported that a kind of prebiotic extracted from marine plants, fucoidans, is helpful in clearing P. aeruginosa from the GI tract of mice by inhibiting the release of some virulence factors and promoting the growth of Bacteroides, whose growth could be suppressed using antibiotic treatment [165].…”