Environmentally Acquired and Their Role in Colonization Resistance.

is an environmentally acquired, anaerobic, spore-forming bacterium which ordinarily causes disease following antibiotic-mediated dysbiosis of the intestinal microbiota. Although much is understood regarding the life cycle of , the fate of spores upon ingestion remains unclear, and the underlying factors that predispose an individual to colonization and subsequent development of infection (CDI) are not fully understood. Here, we show that , a ubiquitous and environmentally acquired, spore-forming bacterium is associated with colonization resistance to .

The toxin candidalysin mediates distinct epithelial inflammatory responses through p38 and EGFR-ERK pathways.

The fungal pathogen secretes the peptide toxin candidalysin, which damages epithelial cells and drives an innate inflammatory response mediated by the epidermal growth factor receptor (EGFR) and mitogen-activated protein kinase (MAPK) pathways and the transcription factor c-Fos. In cultured oral epithelial cells, candidalysin activated the MAPK p38, which resulted in heat shock protein 27 (Hsp27) activation, IL-6 release, and EGFR phosphorylation without affecting the induction of c-Fos. p38 activation was not triggered by EGFR but by two nonredundant pathways involving MAPK kinases (MKKs) and the kinase Src, which differentially controlled p38 signaling outputs.

Candidalysins Are a New Family of Cytolytic Fungal Peptide Toxins.

Candidalysin is the first cytolytic peptide toxin identified in any human fungal pathogen. Candidalysin is secreted by Candida albicans and is critical for driving infection and host immune responses in several model systems. However, infections are also caused by non-C.

Albumin Neutralizes Hydrophobic Toxins and Modulates Pathogenicity.

Albumin is abundant in serum but is also excreted at mucosal surfaces and enters tissues when inflammation increases vascular permeability. Host-associated opportunistic pathogens encounter albumin during commensalism and when causing infections. Considering the ubiquitous presence of albumin, we investigated its role in the pathogenesis of infections with the model human fungal pathogen, Candida albicans.

Role for IL-1 Family Cytokines in Fungal Infections.

Fungal pathogens kill approximately 1.5 million individuals per year and represent a severe disease burden worldwide. It is estimated over 150 million people have serious fungal disease such as recurrent mucosal infections or life-threatening systemic infections.