{"id":{"repo_id":"buffalo","oai_identifier":"oai:ubir.buffalo.edu:10477/78133"},"canonical_url":"https://search.dev.ndltd.org/etd/buffalo/oai:ubir.buffalo.edu:10477/78133","repository":{"repo_id":"buffalo","name":"Buffalo","base_url":"https://ubir.buffalo.edu/oai/request"},"display":{"title":"Fluid flow induces a unique adhesion process and microcolony formation in Candida albicans","abstract":"Ph.D.","abstract_html":"Ph.D.","abstract_has_math":false,"creators":["McCall, Andrew; 0000-0002-3732-5293"],"institution":"State University of New York at Buffalo","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Edgerton, Mira","Oral Biology"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2018,"date_issued":"2018-06-28T20:34:34Z","date_published":"2018-06-28T20:34:34Z","updated_at":"2026-07-27T19:05:09Z","subjects":["microbiology"],"languages":["eng"],"rights":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/10477/78133","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Edgerton, Mira","Oral Biology"]},{"key":"dc:creator","label":"Author","values":["McCall, Andrew; 0000-0002-3732-5293"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2018-06-28T20:34:34Z","2018","2018-05-23 11:12:21"]},{"key":"dc:publisher","label":"Institution","values":["State University of New York at Buffalo"]},{"key":"dc:relation","label":"Dc Relation","values":["Supplementary files: S-Videos.zip (video), supplemental videos with legends"]},{"key":"dc:type","label":"Dc Type","values":["Text","Dissertation"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["microbiology"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/10477/78133"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Ph.D.","Candida albicans is the main causative agent of oropharyngeal candidiasis, a disease of the oral mucosal surfaces that reduces the quality of life for afflicted individuals. The development of numerous in vitro models for C. albicans growth and biofilm development have helped us to gain significant insight into how this organism functions, and how it protects itself from host- derived defenses. One innate host defense that plays an important role in the oral cavity is the mechanical action of flow caused by saliva. While a few in vitro flow models have been developed, these systems have used end-point imaging or quantification and do not allow for the analysis of the dynamic events that occur under fluid flow. Thus, we developed a novel flow system that would allow for real-time imaging and quantification of C. albicans growth and development under flow. We hypothesized that biofilms grown under flow using our system would exhibit a different architecture compared to traditional in vitro biofilms, and that quantification of its dynamic processes would provide novel insights into flow biofilm formation (Chapter 2). We found that C. albicans cells would spontaneously form microcolonies in our flow system at physiological temperatures. These microcolonies are starburst shaped branching filamentous hyphae that grow along the substrate surface from a single mother cell. As the microcolonies grow, they produce lateral budded yeast and pseudohyphae that disperse from the hyphal network. These flow-induced microcolonies more closely resemble the plaque formation that can be seen in many instances of oropharyngeal candidiasis, when compared to traditional in vitro biofilm models. This includes a tendency for these microcolonies to grow well-separated from one another. However, when we analyzed early time points of our data, it appeared that C. albicans cells were initially binding to the surface relatively homogenously, and cells would then detach from the substrate after a short period, leading to the formation of gaps. We hypothesized that this was the result of an unstudied dynamic adhesion process where cells either commit to adherence, or detach from the substrate following an initial attachment event (Chapter 3). By studying the adhesion characteristics over time of knockout strains of various adhesins and regulators of adhesins, as well as hyperfilamentous strains in our flow apparatus, we were able to show that C. albicans cells do adhere in a multi-phase process, including a period of initial attachment prior to commitment to adhesion. Our data also suggests that this commitment to adhesion is related to regulation of hyphal morphogenesis, and that, once committed, adhesion is maintained partially through the action of Ywp1. This makes Ywp1 the first demonstrated adhesion maintenance protein in C. albicans. As we found that our flow-induced microcolonies more closely resembled the plaques of oropharyngeal candidiasis than traditional in vitro biofilms, we were interested in determining the transcriptomic and regulatory elements that distinguish microcolonies from the traditional biofilms (Chapter 4). By comparing the transcriptome our flow-induced microcolonies to two non-microcolony controls, we were able to determine 20 core microcolony response genes, several of which (HWP1, ECE1, HYR1, and PGA10) play a role in the formation of microcolonies. To determine potential regulators, we used a predictive algorithm identify ten transcription factors that regulated at least half of our core microcolony genes. We found that six of these predicted regulators (Sfl1, Sfl2, Efg1, Ndt80, Nrg1, and Rob1) are involved in microcolony formation and function. This profile of transcriptional regulators more closely reflects previously discovered hyphal regulatory networks than biofilm regulatory networks, suggesting that hyphal morphogenesis plays a more central role in the development of flow- induced microcolonies."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Fluid flow induces a unique adhesion process and microcolony formation in Candida albicans"]}]}],"canonical_facts":{"dc:contributor":["Edgerton, Mira","Oral Biology"],"dc:creator":["McCall, Andrew; 0000-0002-3732-5293"],"dc:date":["2018-06-28T20:34:34Z","2018","2018-05-23 11:12:21"],"dc:description":["Ph.D.","Candida albicans is the main causative agent of oropharyngeal candidiasis, a disease of the oral mucosal surfaces that reduces the quality of life for afflicted individuals. The development of numerous in vitro models for C. albicans growth and biofilm development have helped us to gain significant insight into how this organism functions, and how it protects itself from host- derived defenses. One innate host defense that plays an important role in the oral cavity is the mechanical action of flow caused by saliva. While a few in vitro flow models have been developed, these systems have used end-point imaging or quantification and do not allow for the analysis of the dynamic events that occur under fluid flow. Thus, we developed a novel flow system that would allow for real-time imaging and quantification of C. albicans growth and development under flow. We hypothesized that biofilms grown under flow using our system would exhibit a different architecture compared to traditional in vitro biofilms, and that quantification of its dynamic processes would provide novel insights into flow biofilm formation (Chapter 2). We found that C. albicans cells would spontaneously form microcolonies in our flow system at physiological temperatures. These microcolonies are starburst shaped branching filamentous hyphae that grow along the substrate surface from a single mother cell. As the microcolonies grow, they produce lateral budded yeast and pseudohyphae that disperse from the hyphal network. These flow-induced microcolonies more closely resemble the plaque formation that can be seen in many instances of oropharyngeal candidiasis, when compared to traditional in vitro biofilm models. This includes a tendency for these microcolonies to grow well-separated from one another. However, when we analyzed early time points of our data, it appeared that C. albicans cells were initially binding to the surface relatively homogenously, and cells would then detach from the substrate after a short period, leading to the formation of gaps. We hypothesized that this was the result of an unstudied dynamic adhesion process where cells either commit to adherence, or detach from the substrate following an initial attachment event (Chapter 3). By studying the adhesion characteristics over time of knockout strains of various adhesins and regulators of adhesins, as well as hyperfilamentous strains in our flow apparatus, we were able to show that C. albicans cells do adhere in a multi-phase process, including a period of initial attachment prior to commitment to adhesion. Our data also suggests that this commitment to adhesion is related to regulation of hyphal morphogenesis, and that, once committed, adhesion is maintained partially through the action of Ywp1. This makes Ywp1 the first demonstrated adhesion maintenance protein in C. albicans. As we found that our flow-induced microcolonies more closely resembled the plaques of oropharyngeal candidiasis than traditional in vitro biofilms, we were interested in determining the transcriptomic and regulatory elements that distinguish microcolonies from the traditional biofilms (Chapter 4). By comparing the transcriptome our flow-induced microcolonies to two non-microcolony controls, we were able to determine 20 core microcolony response genes, several of which (HWP1, ECE1, HYR1, and PGA10) play a role in the formation of microcolonies. To determine potential regulators, we used a predictive algorithm identify ten transcription factors that regulated at least half of our core microcolony genes. We found that six of these predicted regulators (Sfl1, Sfl2, Efg1, Ndt80, Nrg1, and Rob1) are involved in microcolony formation and function. This profile of transcriptional regulators more closely reflects previously discovered hyphal regulatory networks than biofilm regulatory networks, suggesting that hyphal morphogenesis plays a more central role in the development of flow- induced microcolonies."],"dc:format":["application/pdf"],"dc:identifier":["http://hdl.handle.net/10477/78133"],"dc:language":["eng"],"dc:publisher":["State University of New York at Buffalo"],"dc:relation":["Supplementary files: S-Videos.zip (video), supplemental videos with legends"],"dc:rights":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."],"dc:subject":["microbiology"],"dc:title":["Fluid flow induces a unique adhesion process and microcolony formation in Candida albicans"],"dc:type":["Text","Dissertation"]},"updated_at":"2026-07-27T19:05:09Z"}