Virulence and Biofilm Formation In Candida Albicans Are Inhibited By Short Peptide Subunits of Entv

<p><em>Candida albicans</em>, the most clinically significant fungal pathogen, commonly causes topical mucosal infections such as oral cavity and urogenital tract infections. It also less frequently causes severe invasive and bloodstream infections. Invasive infections are most prevalent amongst patients with compromised innate immune responses, such as those receiving chemotherapy or recovering from surgery. <em>C. albicans</em> can also form biofilms on implanted medical devices. Fungal infections are difficult to treat due to the paucity of therapeutic options, and this problem is compounded by the resistance properties of biofilm infections.</p> <p><em>Candida albicans</em> exists as a member of the commensal flora of the skin and gut where many complex polymicrobial interactions occur with genera such as <em>Pseudomonas </em>and <em>Streptococcus.</em> Some of these interactions potentiate or inhibit virulence. One such interaction is with <em>Enterococcus faecalis</em>, a bacterial gastrointestinal commensal species. <em>E. faecalis </em>produces a small peptide, EntV, that modulates <em>C. albicans </em>virulence. The mature 68-amino acid EntV peptide inhibits biofilm formation <em>in vitro</em> and attenuates fungal virulence in a <em>Caenorhabditis elegans</em> infection model and a murine oral candidiasis model.</p> <p>In this work, I sought to identify the regions of EntV responsible for the anti-fungal activity, and based on structural information, I hypothesized that the activity is localized to a single helix of the mature peptide. In this study, I report that smaller peptides derived from this helix ranging from 12 to 16 amino acids have equal or improved efficacy in inhibiting <em>C. albicans</em> virulence and<em> </em>biofilm formation. These smaller peptides inhibit initial adhesion to abiotic surfaces, reduce final biofilm biomass, and reduce the size of mature biofilms as measured by confocal microscopy. Further trimming of these peptides to fewer than 11 amino acids reduces and eventually eliminates activity. These data indicate that EntV-derived peptides warrant further investigation as potential non-fungicidal additives to medical devices and antifungal therapeutics.</p>

Name thesis:degree_name

Masters of Science (MS)

Level thesis:degree_level

Thesis (MS)

Year dc:date.available

2021

Authors dc:creator

• Cristy, Shane
• <p>https://orcid.org/0000-0001-7316-9331</p>

Contributors dc:contributor

• Michael C. Lorenz
• Danielle A. Garsin
• Theresa M. Koehler

• Candida albicans
• biofilms
• EntV
• antimicrobial peptides
• bacteriocins
• candidiasis
• hyphae
• Medicine and Health Sciences

Repository record dc:identifier

https://digitalcommons.library.tmc.edu/utgsbs_dissertations/1122

OAI identifier oai:identifier

oai:digitalcommons.library.tmc.edu:utgsbs_dissertations-2179