Diarrhea, bacteremia and multiorgan dysfunction due to an extraintestinal pathogenic Escherichia coli strain with enteropathogenic E. coli genes

(c) The Author/sCAUL read and publish agreement 2022fals

Classification and Functional Characterization of Vasa Vasorum-Associated Perivascular Progenitor Cells in Human Aorta

In the microcirculation, pericytes are believed to function as mesenchymal stromal cells (MSCs). We hypothesized that the vasa vasorum harbor progenitor cells within the adventitia of human aorta. Pericytes, endothelial progenitor cells, and other cell subpopulations were detected among freshly isolated adventitial cells using flow cytometry. Purified cultured pericytes were enriched for the MSC markers CD105 and CD73 and depleted of the endothelial markers von Willebrand factor and CD31. Cultured pericytes were capable of smooth muscle lineage progression including inducible expression of smooth muscle myosin heavy chain, calponin, and α-smooth muscle actin, and adopted a spindle shape. Pericytes formed spheroids when cultured on Matrigel substrates and peripherally localized with branching endothelial cells in vitro. Our results indicate that the vasa vasorum form a progenitor cell niche distinct from other previously described progenitor populations in human adventitia. These findings could have important implications for understanding the complex pathophysiology of human aortic disease

A breast cancer stem cell niche supported by juxtacrine signalling from monocytes and macrophages

The cell-biological program termed the epithelial-mesenchymal transition (EMT) confers on cancer cells mesenchymal traits and an ability to enter the cancer stem cell (CSC) state. However, the interactions between CSCs and their surrounding microenvironment are poorly understood. Here we show that tumour-associated monocytes and macrophages (TAMs) create a CSC niche through juxtacrine signalling with CSCs. We performed quantitative proteomic profiling and found that the EMT program upregulates the expression of CD90, also known as Thy1, and EphA4, which mediate the physical interactions of CSCs with TAMs by directly binding with their respective counter-receptors on these cells. In response, the EphA4 receptor on the carcinoma cells activates Src and NF-κ B. In turn, NF-κ B in the CSCs induces the secretion of a variety of cytokines that serve to sustain the stem cell state. Indeed, admixed macrophages enhance the CSC activities of carcinoma cells. These findings underscore the significance of TAMs as important components of the CSC niche.National Institutes of Health (U.S.) (Grant R01-CA078461)National Institutes of Health (U.S.) (Grant P01-CA080111)National Institutes of Health (U.S.) (Grant U54-CA163109

Structure of \u3ci\u3eClostridium difficile\u3c/i\u3e PilJ Exhibits Unprecedented Divergence from Known Type IV Pilins

Type IV pili are produced by many pathogenic Gram-negative bacteria and are important for processes as diverse as twitching motility, cellular adhesion, and colonization. Recently, there has been an increased appreciation of the ability of Gram-positive species, including Clostridium difficile, to produce Type IV pili. Here we report the first three-dimensional structure of a Grampositive Type IV pilin, PilJ, demonstrate its incorporation into Type IV pili, and offer insights into how the Type IV pili of C. difficile may assemble and function. PilJ has several unique structural features, including a dual-pilin fold and the incorporation of a structural zinc ion. We show that PilJ is incorporated into Type IV pili in C. difficile and present a model in which the incorporation of PilJ into pili exposes the C-terminal domain of PilJ to create a novel interaction surface

Structural and Evolutionary Analyses Show Unique Stabilization Strategies in the Type IV Pili of Clostridium difficile

Type IV pili are produced by many pathogenic Gram-negative bacteria and are important for processes as diverse as twitching motility, biofilm formation, cellular adhesion and horizontal gene transfer. However, many Gram-positive species, including C. difficile, also produce Type IV pili. Here, we identify the major subunit of the Type IV pili of C. difficile, PilA1, and describe multiple three-dimensional structures of PilA1, demonstrating the diversity found in three strains of C. difficile. We also model the incorporation of both PilA1 and a minor pilin, PilJ, into the pilus fiber. Although PilA1 contains no cysteine residues, and therefore cannot form the disulfide bonds found in all Gram-negative Type IV pilins, it adopts unique strategies to achieve a typical pilin fold. The structures of PilA1 and PilJ exhibit similarities with the Type IVb pilins from Gram-negative bacteria that suggest that the Type IV pili of C. difficile are involved in microcolony formation

Uropathogenic Escherichia coli (UPEC) strains may carry virulence properties of diarrhoeagenic E-coli

To analyze whether Escherichia coli strains that cause urinary tract infections (UPEC) share virulence characteristics with the diarrheagenic E. coli (DEC) pathotypes and to recognize their genetic diversity, 225 UPEC strains were examined for the presence of various properties of DEC and UPEC (type of interaction with HeLa cells, serogroups and presence of 30 virulence genes). No correlation between adherence patterns and serogroups was observed. Forty-five serogroups were found, but 64% of the strains belonged to one of the 12 serogroups (O1, O2, O4, O6, O7, O14, O15, O18, O21, O25, O75, and O175) and carried UPEC virulence genes (pap, hly, aer, sfa, cnf). the DEC genes found were: aap, aatA, aggC, agg3C, aggR, astA, eae, ehly, iha, irp2, lpfA(O113), pet, pic, pilS, and shf. Sixteen strains presented aggregative adherence and/or the aatA sequence, which are characteristics of enteroaggregative E. coli (EAEC), one of the DEC pathotypes. in summary, certain UPEC strains may carry DEC virulence properties, mostly associated to the EAEC pathotype. This finding raises the possibility that at least some faecal EAEC strains might represent potential uropathogens. Alternatively, certain UPEC strains may have acquired EAEC properties, becoming a potential cause of diarrhoea.Universidade Federal de São Paulo, Escola Paulista Med, Dept Microbiol Immunol & Parasitol, BR-04023062 São Paulo, BrazilUniv Santiago de Compostela, Fac Vet, Dept Microbiol & Parasitol, Lab Referencia E Coli, Lugo, SpainUniversidade Federal de São Paulo, Lab Cent Hosp São Paulo, São Paulo, BrazilInst Butantan, Bacteriol Lab, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Microbiol Immunol & Parasitol, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Lab Cent Hosp São Paulo, São Paulo, BrazilWeb of Scienc