Background: The luxS/AI-2 signaling pathway has been reported to interfere with important physiological and pathogenic functions in a variety of bacteria. In the present study, we investigated the functional role of the streptococcal luxS/AI-2 system in metabolism and diverse aspects of pathogenicity including the adaptation of the organism to stress conditions using two serotypes of Streptococcus pyogenes, M1 and M19. Results: Exposing wild-type and isogenic luxS-deficient strains to sulfur-limited media suggested a limited role for luxS in streptococcal activated methyl cycle metabolism. Interestingly, loss of luxS led to an increased acid tolerance in both serotypes. Accordingly, luxS expression and AI-2 production were reduced at lower pH, thus linking the luxS/AI-2 system to stress adaptation in S. pyogenes. luxS expression and AI-2 production also decreased when cells were grown in RPMI medium supplemented with 10% serum, considered to be a host environment-mimicking medium. Furthermore, interaction analysis with epithelial cells and macrophages showed a clear advantage of the luxS-deficient mutants to be internalized and survive intracellularly in the host cells compared to the wild-type parents. In addition, our data revealed that luxS influences the expression of two virulence-associated factors, the fasX regulatory RNA and the virulence gene sibA (psp). Conclusion: Here, we suggest that the group A streptococcal luxS/AI-2 system is not only involved in the regulation of virulence factor expression but in addition low level of luxS expression seems to provide an advantage for bacterial survival in conditions that can be encountered during infections.

Streptococcus pneumoniae infection is a leading cause of morbidity and mortality worldwide. One of the most severe complications of invasive pneumococcal disease (IPD) is haemolytic uraemic syndrome (HUS). This study was undertaken to determine the risk factors and role of pneumococcal neuraminidases in HUS in children with IPD. Eighteen cases of HUS and 54 patients with IPD without HUS were identified. The controls were patients with culture-confirmed IPD without HUS. Clinical and laboratory characteristics of the two groups of patients were compared. Bacterial isolates from both groups were serotyped, sequence typed and examined for their carriage of three neuraminidase genes. Necrotizing pneumonia and serotype 3 infection were significantly associated with HUS in children with IPD, suggesting that a severe pulmonary suppurating disease increase the risk of HUS. Serotype 14 was associated with necrotizing pneumonia but not HUS. Children with HUS were more likely to require surgery and had a longer duration of hospitalization. The study identified a significantly higher carriage of a neuraminidase gene, nanC, in the causative pneumococcal isolates from patients with HUS (89% versus 41%, p 0.001). The sensitivity and specificity of nanC to predict HUS were 89% and 59%, respectively. In conclusion, necrotizing pneumonia, serotype 3 infection and neuraminidase gene nanC were associated with HUS in children with IPD. The result suggests that NanC could provide an additive effect to NanA and NanB in the overall activity of pneumococcal neuraminidases to expose Thomsen–Friedenreich antigen on various cells in patients with HUS.

Background: Pseudomonas aeruginosaintestinal 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 decolonizeP. aeruginosafrom 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 forP. aeruginosagastrointestinal 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 ofBacteroides(post-infection day-3 abundance, 29–50%) and consequential reductions in bloom ofEnterobacteriaceaeandEnterococcaceaepopulations. In the non-supplemented group,Parabacteroidesmediated recovery from dysbiosis but failed to decolonizeP. aeruginosa.Conclusions: Supplementing diet with marine prebiotic fucoidans can mediate earlier recovery from dysbiosis and decolonization ofP. aeruginosafrom gut by inhibiting secreted virulence factor (TpsA/CdiA) interaction with mucins and promoting the growth of beneficialBacteroidespopulation. We suggest the prophylactic use of nutritional grade fucoidans to decolonizeP. aeruginosafrom gastrointestinal tract of at-risk individuals to prevent infection and transmission of colonizingP. aeruginosa.