ETEC colonisation factors disrupt the antigen presenting capacity of porcine intestinal dendritic cells

Enterotoxigenic E. coli (ETEC) are not only a major cause of diarrhoea in travellers to and children in developing countries, but also cause neonatal and postweaning diarrhoea in piglets, leading to a reduced feed conversion and a higher mortality rate. As a consequence ETEC infections result in severe economic losses in the swine production industry. This intestinal pathogen displays colonisation factors or fimbriae on its surface enabling the microorganism to adhere to the intestinal epithelium (Fig. 1). In pig, F4 and F18 fimbriae are the most frequently associated with ETEC-induced diarrhoea1. As opposed to F4 fimbriae, oral immunisation with F18 fimbriae doesn’t protect piglets from a subsequent challenge infection2. F18 fimbriae bind glycosphingolipids in the apical membrane of enterocytes, but no transcytosis occurs, resulting in lower sunepithelial antigen concentrations as compared to F4 fimbriae, which bind the transcytotic receptor aminopeptidase N3,4. However, M-cell mediated transport of F18 fimbriae should still occur. Hence, besides a lower antigen concentration, these fimbriae could affect the function of intestinal antigen presenting cells. Here, we investigated the influence of purified F18 fimbriae on the antigen presentation capacity of small intestinal lamina propria dendritic cells (LPDCs)

Comparative proteomics of uropathogenic Escherichia coli during growth in human urine identify UCA-like (UCL) fimbriae as an adherence factor involved in biofilm formation and binding to uroepithelial cells

Uropathogenic Escherichia coli (UPEC) are the primary cause of urinary tract infection (UTI) in humans. For the successful colonisation of the human urinary tract, UPEC employ a diverse collection of secreted or surface-exposed virulence factors including toxins, iron acquisition systems and adhesins. In this study, a comparative proteomic approach was utilised to define the UPEC pan and core surface proteome following growth in pooled human urine. Identified proteins were investigated for subcellular origin, prevalence and homology to characterised virulence factors. Fourteen core surface proteins were identified, as well as eleven iron uptake receptor proteins and four distinct fimbrial types, including type 1, P, F1C/S and a previously uncharacterised fimbrial type, designated UCA-like (UCL) fimbriae in this study. These pathogenicity island (PAI)-associated fimbriae are related to UCA fimbriae of Proteus mirabilis, associated with UPEC and exclusively found in members of the E. coli B2 and D phylogroup. We further demonstrated that UCL fimbriae promote significant biofilm formation on abiotic surfaces and mediate specific attachment to exfoliated human uroepithelial cells. Combined, this study has defined the surface proteomic profiles and core surface proteome of UPEC during growth in human urine and identified a new type of fimbriae that may contribute to UTI

The adjuvant effect of Gantrez®AN nanoparticles on oral vaccination of pigs and mice with F4 fimbriae is strongly influenced by polymer degradation

We analysed the adjuvant effect of Gantrez nanoparticles NP on oral immunisation of pigs and mice with F4 fimbriae. The animals were vaccinated with F4, F4 encapsulated in Gantrez NP, called gF4 NP, or F4 + empty Gantrez NP, called F4 + gNP, and intragastrically infected with F4+ ETEC. The adjuvant effect of Gantrez®AN nanoparticles on oral vaccination of pigs and mice with F4 fimbriae is strongly influenced by polymer degradation

Std fimbriae-fucose interaction increases Salmonella-induced intestinal inflammation and prolongs colonization

Author summary The intestinal epithelium is a crucial biological interface, interacting with both commensal and pathogenic microorganisms. It’s lined with heavily glycosylated proteins and glycolipids which can act as both attachment sites and energy sources for intestinal bacteria. Fut2, the enzyme governing epithelial α1,2-fucosylation, has been implicated in the interaction between microbes and intestinal epithelial cells. Salmonella is one of the most important bacterial gastrointestinal pathogens affecting millions of people worldwide. Salmonella possesses fimbrial and non-fimbrial adhesins which can be used to adhere to host cells. Here we show that Salmonella expresses Std fimbriae in the gastrointestinal tract in vivo and exploit Std fimbriae to bind fucosylated structures in the mucus and on the intestinal epithelium. Furthermore, we demonstrate that the Std fimbriae-fucose interaction is necessary for bacterial colonization of the intestine and for triggering intestinal inflammation. These data lend new insights into bacterial adhesion-epithelial interactions which are essential for bacterial pathogenesis and key factors in determining tissue tropism and host susceptibility to infectious disease

Proteus sp. – an opportunistic bacterial pathogen – classification, swarming growth, clinical significance and virulence factors

The genus Proteus belongs to the Enterobacteriaceae family, where it is placed in the tribe Proteeae, together with the genera Morganella and Providencia. Currently, the genus Proteus consists of five species: P. mirabilis, P. vulgaris, P. penneri, P. hauseri and P. myxofaciens, as well as three unnamed Proteus genomospecies. The most defining characteristic of Proteus bacteria is a swarming phenomenon, a multicellular differentiation process of short rods to elongated swarmer cells. It allows population of bacteria to migrate on solid surface. Proteus bacteria inhabit the environment and are also present in the intestines of humans and animals. These microorganisms under favorable conditions cause a number of infections including urinary tract infections (UTIs), wound infections, meningitis in neonates or infants and rheumatoid arthritis. Therefore, Proteus is known as a bacterial opportunistic pathogen. It causes complicated UTIs with a higher frequency, compared to other uropathogens. Proteus infections are accompanied by a formation of urinary stones, containing struvite and carbonate apatite. The virulence of Proteus rods has been related to several factors including fimbriae, flagella, enzymes (urease - hydrolyzing urea to CO2 and NH3, proteases degrading antibodies, tissue matrix proteins and proteins of the complement system), iron acqusition systems and toxins: hemolysins, Proteus toxin agglutinin (Pta), as well as an endotoxin - lipopolysaccharide (LPS). Proteus rods form biofilm, particularly on the surface of urinary catheters, which can lead to serious consequences for patients. In this review we present factors involved in the regulation of swarming phenomenon, discuss the role of particular pathogenic features of Proteus spp., and characterize biofilm formation by these bacteria

Nanobody mediated inhibition of attachment of F18 fimbriae expressing Escherichia coli

Post-weaning diarrhea and edema disease caused by F18 fimbriated E. coli are important diseases in newly weaned piglets and lead to severe production losses in farming industry. Protective treatments against these infections have thus far limited efficacy. In this study we generated nanobodies directed against the lectin domain of the F18 fimbrial adhesin FedF and showed in an in vitro adherence assay that four unique nanobodies inhibit the attachment of F18 fimbriated E. coli bacteria to piglet enterocytes. Crystallization of the FedF lectin domain with the most potent inhibitory nanobodies revealed their mechanism of action. These either competed with the binding of the blood group antigen receptor on the FedF surface or induced a conformational change in which the CDR3 region of the nanobody displaces the D ''-E loop adjacent to the binding site. This D ''-E loop was previously shown to be required for the interaction between F18 fimbriated bacteria and blood group antigen receptors in a membrane context. This work demonstrates the feasibility of inhibiting the attachment of fimbriated pathogens by employing nanobodies directed against the adhesin domain

Comparison of immune responses in parenteral FaeG DNA primed pigs boosted orally with F4 protein or reimmunized with the DNA vaccine

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The long polar fimbriae (lpf) operon and its flanking regions in bovine Escherichia coli O157:H43 and STEC O136:H12 strains

Long polar fimbriae (Lpf) are intestinal adhesins and important virulence factors of pathogenic Escherichia coli strains. We cloned and sequenced the lpf2-1 operon (lpf2ABCD) and its flanking regions of an intimin- and Shiga toxin-negative E. coli O157:H43 strain from bovine origin, and also sequenced the lpf2-1 operon of 6 additional atypical O157 bovine Escherichia coli strains of various serotypes Nucleotide sequence comparison of these lpf operons showed sequence conservation as they contain only four polymorphic nucleotide positions. Investigation of these O157 strains as well as 13 Escherichia coli Reference Collection (ECOR) strains carrying the lpf2-1 allele revealed high degree of sequence conservation in the lpf2 flanking regions. The lpf2-1 allele is also present in a bovine Shiga toxin-producing E. coli STEC O136:H12 strain and in vitro adherence assays revealed that the absence of lpf2-1 in this strain did not affect its host cell-binding properties. Our data indicate that lpf2 loci is highly conserved in E. coli isolates, but its role in adherence might be masked by other uncharacterized adhesins