Biology subjects

Staab, J. F.

Publications and source records attributed to Staab, J. F..

2 recordsLinked to original sources

bioRxiv2026

Candida albicans promotes self-adhesion and tumor cell progression of colorectal cancer cells.

Candida albicans, a benign commensal yeast in the healthy gut, is increasingly being recognized as a tumor-promoting component of the gut mycobiome that is linked to worse patient outcomes in colorectal cancer (CRC). Emerging evidence suggests that in the tumor microenvironment, C. albicans drives tumor progression in its pathogenic hyphal form with the secretion of its peptide toxin, candidalysin, enhancing tumor cell evolution. CRC cells differentially express transglutaminase 2 (TG2), which mediates covalent binding to C. albicans and can promote tumor adaptability and metastases. However, mechanistic insight into how C. albicans infection leads to CRC progression is incomplete. CRC lines that express high (SW480) and low (LoVo, HCT 116) TG2 were infected with C. albicans and examined for effects on epithelial to mesenchymal transition (EMT) and cell migration. Parallel studies were also conducted using a candidalysin-deficient C. albicans strain. C. albicans invasion stimulated TG2 activity that allowed covalent crosslinking of the hyphae adhesin, Hwp1, to SW480 cells in a candidalysin-dependent manner. Independent of TG2 expression, infection of SW480, LoVo, and HCT 116 cells induced EMT-like changes including downregulation of E-cadherin, altered N-glycosylation of N-cadherin, and variable Snail1 expression. Infection increased MGAT5 activity, which raised levels of branched {beta}(1-6) N-glycans. Infection promoted CRC cell motility that was blocked by pharmacological inhibition of MGAT5. Thus, C. albicans engages CRC cells through separable mechanisms: a candidalysin-TG2-Hwp1 axis that may stabilize fungal attachment in TG2-high tumor cells, and a TG2-independent program of epithelial plasticity, altered N-glycosylation and migration-associated behavior that requires validation in vivo.

microbiology↗

bioRxiv2020

Coronin-1 is necessary for enteric pathogen-induced transcytosis across human ileal enteroid monolayers expressing M cells

In the intestine, luminal sampling by microfold (M) cells is crucial for inducing protective mucosal immune responses but can also serve as an entry pathway for pathogens, including bacteria and viruses. Enteric pathogens can influence intestinal M cell function; however, the molecular mechanisms involved in the regulation of uptake and transcytosis of gut cargo by human M cells remain to be determined. Understanding the mechanisms responsible for regulating human M cell function requires a relevant human model. In this study, human ileal enteroids established from healthy donors were grown as confluent monolayers on permeable supports and differentiated to express mature M cells. Enteric pathogens including enteropathogenic E. coli (EPEC), adherent invasive E. coli (AIEC), and human rotavirus were apically exposed to M cell enteroid monolayers. M cell-mediated uptake and transcytosis was compared in enteroids infected by pathogenic or commensal bacteria (HS strain). EPEC and AIEC, but not HS, stimulated M cell uptake and transcytosis. We discovered that this pathogenspecific effect was dependent on expression of coronin 1a, a cytoskeletal remodeling protein. Using stable coronin 1a knockdown (KD) enteroids, we observed that EPEC-stimulated transcytosis of fluorescent beads was lost and associated with a significant decrease in the number of glycoprotein-2 positive (Gp-2+ve) M cells. The results of these studies demonstrate that coronin 1a is required for uptake and transcytosis of luminal cargo across human M cells and that coronin 1a is necessary for differentiation of mature M cells that actively transcytose luminal gut antigens in response to pathogenic, but not commensal, microbes.

cell biology↗