scholarly journals The Antibiotic Bacitracin Protects Human Intestinal Epithelial Cells and Stem Cell-Derived Intestinal Organoids from Clostridium difficile Toxin TcdB

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Ziyu Zhu ◽  
Leonie Schnell ◽  
Bastian Müller ◽  
Martin Müller ◽  
Panagiotis Papatheodorou ◽  
...  
Keyword(s):  
Stem Cell ◽  
Epithelial Cells ◽  
Inhibitory Effect ◽  
Target Cells ◽  
Intestinal Epithelial ◽  
Intestinal Organoids ◽  
Human Intestinal Epithelial Cells ◽  
Protein Toxins ◽  
Dependent Transport

Bacitracin is an established antibiotic for local application and inhibits the cell wall synthesis of Gram-positive bacteria. Recently, we discovered a completely different mode of action of bacitracin and reported that this drug protects human cells from intoxication by a variety of medically relevant bacterial protein toxins including CDT, the binary actin ADP-ribosylating toxin of Clostridium (C.) difficile. Bacitracin prevents the transport of CDT into the cytosol of target cells, most likely by inhibiting the transport function of the binding subunit of this toxin. Here, we tested the effect of bacitracin towards TcdB, a major virulence factor of C. difficile contributing to severe C. difficile-associated diseases (CDAD) including pseudomembranous colitis. Bacitracin protected stem cell-derived human intestinal organoids as well as human gut epithelial cells from intoxication with TcdB. Moreover, it prevented the TcdB-induced disruption of epithelia formed by gut epithelium cells in vitro and maintained the barrier function as detected by measuring transepithelial electrical resistance (TEER). In the presence of bacitracin, TcdB was not able reach its substrate Rac1 in the cytosol of human epithelial cells, most likely because its pH-dependent transport across cell membranes into the cytosol is decreased by bacitracin. In conclusion, in addition to its direct antibiotic activity against C. difficile and its inhibitory effect towards the toxin CDT, bacitracin neutralizes the exotoxin TcdB of this important pathogenic bacterium.

Efficacy of Plant-Derived Antimicrobials in Controlling Enterohemorrhagic Escherichia coli Virulence In Vitro

2016 ◽  
Vol 79 (11) ◽  
pp. 1965-1970 ◽  
Author(s):  
SANGEETHA ANANDA BASKARAN ◽  
ANUP KOLLANOOR-JOHNY ◽  
MEERA SURENDRAN NAIR ◽  
KUMAR VENKITANARAYANAN
Keyword(s):  
Escherichia Coli ◽  
Epithelial Cells ◽  
Antimicrobial Agents ◽  
Intestinal Epithelial Cells ◽  
Enterohemorrhagic Escherichia Coli ◽  
Host Cells ◽  
Intestinal Epithelial ◽  
Virulence Gene Expression ◽  
Human Intestinal Epithelial Cells

ABSTRACTEscherichia coli O157:H7 is a major foodborne pathogen that can cause serious human illness characterized by hemorrhagic diarrhea and kidney failure. The pathology of enterohemorrhagic E. coli O157:H7 (EHEC) infection is primarily mediated by verotoxins, which bind to the globotriaosylceramide receptor on host cells. Antibiotics are contraindicated for treating EHEC infection because they lead to increased verotoxin release, thereby increasing the risk of renal failure and death in patients. Thus, alternative strategies are needed for controlling EHEC infections in humans. This study investigated the effect of subinhibitory concentrations of five plant-derived antimicrobial agents (PDAs) that are generally considered as safe, i.e., trans-cinnamaldehyde, eugenol, carvacrol, thymol, and β-resorcylic acid, on EHEC motility, adhesion to human intestinal epithelial cells, verotoxin production, and virulence gene expression. All tested PDAs reduced EHEC motility and attachment to human intestinal epithelial cells (P < 0.05) and decreased verotoxin synthesis by EHEC. The reverse transcription real-time PCR data revealed that PDAs decreased the expression of critical virulence genes in EHEC (P < 0.05). The results collectively suggest that these PDAs could be used to reduce EHEC virulence, but follow-up studies in animal models are necessary to validate these findings.

scholarly journals Characterization of Candidate Live Oral Salmonella typhi Vaccine Strains Harboring Defined Mutations inaroA, aroC, and htrA

1999 ◽  
Vol 67 (2) ◽  
pp. 700-707 ◽  
Author(s):  
David C. Lowe ◽  
Tor C. Savidge ◽  
Derek Pickard ◽  
Lars Eckmann ◽  
Martin F. Kagnoff ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Salmonella Typhi ◽  
Scid Mice ◽  
Intestinal Epithelial ◽  
Human Intestinal Epithelial Cells ◽  
U937 Macrophage ◽  
Ht 29

ABSTRACT The properties of two candidate Salmonella typhi-based live oral typhoid vaccine strains, BRD691 (S. typhi Ty2 harboring mutations in aroA and aroC) and BRD1116 (S. typhi Ty2 harboring mutations inaroA, aroC, and htrA), were compared in a number of in vitro and in vivo assays. BRD1116 exhibited an increased susceptibility to oxidative stress compared with BRD691, but both strains were equally resistant to heat shock. Both strains showed a similar ability to invade Caco-2 and HT-29 epithelial cells and U937 macrophage-like cells, but BRD1116 was less efficient at surviving in epithelial cells than BRD691. BRD1116 and BRD691 were equally susceptible to intracellular killing within U937 cells. Similar findings were demonstrated in vivo, with BRD1116 being less able to survive and translocate to secondary sites of infection when inoculated into the lumen of human intestinal xenografts in SCID mice. However, translocation of BRD1116 to spleens and livers in SCID mice occurred as efficiently as that of BRD691 when inoculated intraperitonally. The ability of BRD1116 to increase the secretion of interleukin-8 following infection of HT-29 epithelial cells was comparable to that of BRD691. Therefore, loss of the HtrA protease inS. typhi does not seem to alter its ability to invade epithelial cells or macrophages or to induce proinflammatory cytokines such as IL-8 but significantly reduces intracellular survival in human intestinal epithelial cells in vitro and in vivo.

scholarly journals Carrageenan Induces Cell Cycle Arrest in Human Intestinal Epithelial Cells in Vitro

2008 ◽  
Vol 138 (3) ◽  
pp. 469-475 ◽  
Author(s):  
Sumit Bhattacharyya ◽  
Alip Borthakur ◽  
Pradeep K. Dudeja ◽  
Joanne K. Tobacman
Keyword(s):  
Cell Cycle ◽  
Epithelial Cells ◽  
Cell Cycle Arrest ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial ◽  
Cycle Arrest ◽  
Human Intestinal Epithelial Cells

scholarly journals The influence of microbial metabolites on human intestinal epithelial cells and macrophages in vitro

2005 ◽  
Vol 45 (2) ◽  
pp. 183-189 ◽  
Author(s):  
Marleen H.M.C. Nuenen ◽  
Rianne A.F. Ligt ◽  
Robert P. Doornbos ◽  
Janneke C.J. Woude ◽  
Ernst J. Kuipers ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial ◽  
Microbial Metabolites ◽  
Human Intestinal Epithelial Cells

scholarly journals Expression of Human Decay-Accelerating Factor on Intestinal Epithelium of Transgenic Mice Does Not Facilitate Infection by the Enteral Route

2015 ◽  
Vol 89 (8) ◽  
pp. 4311-4318 ◽  
Author(s):  
Jieyan Pan ◽  
Lili Zhang ◽  
Matthew A. Odenwald ◽  
Le Shen ◽  
Jerrold R. Turner ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Transgenic Mice ◽  
Intestinal Epithelium ◽  
Intestinal Epithelial Cells ◽  
Apical Cell ◽  
Oral Route ◽  
Intestinal Epithelial ◽  
Human Intestinal Epithelial Cells ◽  
Cvb3 Infection

ABSTRACTIn vitro, infection of polarized human intestinal epithelial cells by coxsackievirus B3 (CVB3) depends on virus interaction with decay-accelerating factor (DAF), a receptor expressed on the apical cell surface. Although mice are highly susceptible to CVB3 infection when virus is delivered by intraperitoneal injection, infection by the enteral route is very inefficient. Murine DAF, unlike human DAF, does not bind virus, and we hypothesized that the absence of an accessible receptor on the intestinal surface is an important barrier to infection by the oral route. We generated transgenic mice that express human DAF specifically on intestinal epithelium and measured their susceptibility to infection by a DAF-binding CVB3 isolate. Human DAF permitted CVB3 to bind to the intestinal surfaceex vivoand to infect polarized monolayers of small-intestinal epithelial cells derived from DAF transgenic mice. However, expression of human DAF did not facilitate infection by the enteral route either in immunocompetent animals or in animals deficient in the interferon alpha/beta receptor. These results indicate that the absence of an apical receptor on intestinal epithelium is not the major barrier to infection of mice by the oral route.IMPORTANCECVB3 infection of human intestinal epithelial cells depends on DAF at the apical cell surface, and expression of human DAF on murine intestinal epithelial cells permits their infectionin vitro. However, expression of human DAF on the intestinal surface of transgenic mice did not facilitate infection by the oral route. Although the role of intestinal DAF in human infection has not been directly examined, these results suggest that DAF is not the critical factor in mice.

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