Biology subjects

Petkau, K.

Publications and source records attributed to Petkau, K..

3 recordsLinked to original sources

bioRxiv2019

Symbiotic Lactobacillus brevis promote stem cell expansion and tumorigenesis in the Drosophila intestine.

Microbial factors influence homeostatic and oncogenic growth in the intestinal epithelium. However, we know little about immediate effects of commensal bacteria on stem cell division programs. In this study, we examined effects of commensal Lactobacillus species on homeostatic, and tumorigenic stem cell growth in the Drosophila intestine. We identified Lactobacillus brevis as a potent stimulator of stem cell growth. In a wildtype midgut, Lactobacillus brevis activates growth regulatory pathways that drive stem cell divisions. In a Notch-deficient background, Lactobacillus brevis-mediated growth causes rapid expansion of mutant progenitors, leading to accumulation of large, multi-layered tumors throughout the midgut. Mechanistically, we showed that Lactobacillus brevis disrupts expression and subcellular distribution of progenitor cell integrins, supporting symmetric divisions that expand intestinal stem cell populations. Collectively, our data emphasize the impact of commensal microbes on growth and maintenance of the intestinal progenitor compartment.

cell biology↗

bioRxiv2019

Complex symbiont-pathogen interactions inhibit intestinal repair

Pathogen-mediated damage to the intestinal epithelium activates compensatory growth and differentiation repair programs in progenitor cells. Accelerated progenitor growth replenishes damaged tissue and maintains barrier integrity. Despite the importance of epithelial renewal to intestinal homeostasis, we know little about the effects of pathogen-commensal interactions on progenitor growth. We found that the enteric pathogen Vibrio cholerae, blocks critical growth and differentiation pathways in Drosophila progenitors despite extensive damage to the epithelial tissue. We showed that inhibition of epithelial repair requires interactions of the Vibrio cholerae type six secretion system with a complex community of symbiotic bacteria, and that elimination of the gut microbiome is sufficient to restore homeostatic growth in infected intestines. Together, this work highlights the importance of pathogen-symbiont interactions on intestinal immune responses and outlines a previously undescribed impact of the type six secretion system on pathogenesis.

immunology↗

bioRxiv2016

Constitutive Immune Activity Promotes Tumorigenesis in Drosophila Intestinal Progenitor Cells.

Gut innate immune defenses contain bacterial populations and protect the host interior from invasive microbes. Although excess intestinal immune activity frequently promotes inflammatory illnesses, we know little about the consequences of chronic innate immune activity exclusively in endodermal gut cells of an otherwise normal animal. To address this question, we generated a transgenic line that allows us to activate inflammatory signals in adult fly intestinal progenitor cells. We found that constitutive immune activity in intestinal progenitors disrupts expression of homeostatic regulators such as Notch signal transduction pathway components and induces hyperplasia throughout the gut. Consistent with these observations, we found that persistent immune signaling interferes with progenitor cell differentiation and exacerbates the formation of Notch-dependent intestinal tumors. These findings uncover a novel link between constitutive immune activity and tumorigenesis in intestinal stem cells.

immunology↗