{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/115511"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/115511","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Coexistence of paralogous quorum sensing systems leads to diverse network topology for coordinating competence and bacteriocin biosynthesis in cariogenic streptococci","abstract":"Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2024-05-01","abstract_html":"Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2024-05-01","abstract_has_math":false,"creators":["Li, Jinbei"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Bioengineering","degree_department":null,"school":null,"contributors":["Jensen, Paul","Metcalf, William","Perez-Pinera, Pablo","Sirk, Shannon"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2022,"date_issued":"2022-05","date_published":"2022-05","updated_at":"2026-07-22T22:24:54Z","subjects":["Streptococci","quorum sensing","natural competence","transcriptional network","paralogous systems","bacterial evolution","oral bacteria"],"languages":["en","eng"],"rights":["Copyright 2022 Jinbei Li"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/2142/115511","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Jensen, Paul","Metcalf, William","Perez-Pinera, Pablo","Sirk, Shannon"]},{"key":"dc:creator","label":"Author","values":["Li, Jinbei"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2022-05","2022-03-10"]},{"key":"dc:type","label":"Dc Type","values":["text","Thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Bioengineering"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Illinois at Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Streptococci","quorum sensing","natural competence","transcriptional network","paralogous systems","bacterial evolution","oral bacteria"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en","eng"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright 2022 Jinbei Li"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://hdl.handle.net/2142/115511"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2024-05-01","The student, Jinbei Li, accepted the attached license on 2022-03-06 at 18:36.","The student, Jinbei Li, submitted this Dissertation for approval on 2022-03-06 at 18:43.","This Dissertation was approved for publication on 2022-03-10 at 17:00.","DSpace SAF Submission Ingestion Package generated from Vireo submission #17525 on 2022-11-11 at 11:55:48","This thesis consists of two parts that encapsulate the three-year PhD career of the authors, starting with a challenge-driven project that was successfully accomplished, and morphing into a curiosity-driven project that yielded surprising and potentially impactful intellectual fruits. It started with the challenge to transform Streptococcus sobrinus, known as one of the two important bacterial species that cause dental caries (tooth decay) in humans. Our knowledge of S. sobrinus is scant despite its important role in oral health. It is widely believed that S. sobrinus lacks the natural competence pathways that are used by other streptococci to regulate growth, virulence, and quorum sensing. The lack of natural competence has also prevented genetic manipulation of S. sobrinus, limiting our knowledge of its pathogenicity. We discovered most strains of S. sobrinus contain a new class of the ComRS competence system. Although S. sobrinus is typically placed among the mutans group streptococci, the S. sobrinus ComRS system is most similar to the competence pathways in the salivarius group. Unlike all other ComRS systems, the S. sobrinus pathway contains two copies of the transcriptional regulator ComR and has a peptide pheromone (XIP) that lacks any aromatic amino acids. Synthetic XIP allows transformation of S. sobrinus with plasmid or linear DNA, and we leverage this newfound genetic tractability to confirm that only one of the ComR homologs is required for induced competence while the other appears to suppress competence. Exogenous XIP increases the expression of bacteriocin gene clusters and produces an antimicrobial response that inhibits growth of S. mutans. We also identified two strains of S. sobrinus that appear to be “cheaters\" by either not responding to or not producing XIP. We show how a recombination event in the non-responsive strain could restore function of the ComRS pathway but delete the gene encoding XIP. Thus the S. sobrinus ComRS pathway provides new tools for studying this pathogen and offers a lens into the evolution of ecological cheaters. The discovery of S. sobrinus ComRS system led us to analyze ComRS networks in all seven cariogenic streptococci. We found that most of them possess two paralogous ComRS systems. We expanded genetic tractability from only one species (Streptococcus mutans) to six of the seven streptococci, and dissected the ComRS network structures in detail for five. A high level of diversity is observed in these ComRS networks. Our results serve as a major expansion of the ComRS system paradigm. Of particular significance is the disentanglement of the dual-ComRS network in S. mutans, whose Type II ComRS network has been the primary ComRS system model. We show S. mutans has two paralogous ComRS systems with bidirectional crosstalk. We discovered that ComRS promoter specificity depends on the sequence of the promoter, providing a basis for the separation and crosstalk in S. mutans and S. sobrinus ComRS networks. In S. mutans, even a single base pair change could potentially lead to complete integration of the two systems. The diversity of dual-ComRS networks revealed in this study depends on the presence of two paralogous systems and is facilitated by the modularity of different network components. While natural competence is important for genome adaptability, the flexibility in natural competence-regulating networks may provide an added layer of adaptability on top. We envision that paralogous regulatory systems may be used as a strategy in engineering biology to either generate network structure libraries or to easily modulate network outcomes."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Coexistence of paralogous quorum sensing systems leads to diverse network topology for coordinating competence and bacteriocin biosynthesis in cariogenic streptococci"]}]}],"canonical_facts":{"dc:contributor":["Jensen, Paul","Metcalf, William","Perez-Pinera, Pablo","Sirk, Shannon"],"dc:creator":["Li, Jinbei"],"dc:date":["2022-05","2022-03-10"],"dc:description":["Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2024-05-01","The student, Jinbei Li, accepted the attached license on 2022-03-06 at 18:36.","The student, Jinbei Li, submitted this Dissertation for approval on 2022-03-06 at 18:43.","This Dissertation was approved for publication on 2022-03-10 at 17:00.","DSpace SAF Submission Ingestion Package generated from Vireo submission #17525 on 2022-11-11 at 11:55:48","This thesis consists of two parts that encapsulate the three-year PhD career of the authors, starting with a challenge-driven project that was successfully accomplished, and morphing into a curiosity-driven project that yielded surprising and potentially impactful intellectual fruits. It started with the challenge to transform Streptococcus sobrinus, known as one of the two important bacterial species that cause dental caries (tooth decay) in humans. Our knowledge of S. sobrinus is scant despite its important role in oral health. It is widely believed that S. sobrinus lacks the natural competence pathways that are used by other streptococci to regulate growth, virulence, and quorum sensing. The lack of natural competence has also prevented genetic manipulation of S. sobrinus, limiting our knowledge of its pathogenicity. We discovered most strains of S. sobrinus contain a new class of the ComRS competence system. Although S. sobrinus is typically placed among the mutans group streptococci, the S. sobrinus ComRS system is most similar to the competence pathways in the salivarius group. Unlike all other ComRS systems, the S. sobrinus pathway contains two copies of the transcriptional regulator ComR and has a peptide pheromone (XIP) that lacks any aromatic amino acids. Synthetic XIP allows transformation of S. sobrinus with plasmid or linear DNA, and we leverage this newfound genetic tractability to confirm that only one of the ComR homologs is required for induced competence while the other appears to suppress competence. Exogenous XIP increases the expression of bacteriocin gene clusters and produces an antimicrobial response that inhibits growth of S. mutans. We also identified two strains of S. sobrinus that appear to be “cheaters\" by either not responding to or not producing XIP. We show how a recombination event in the non-responsive strain could restore function of the ComRS pathway but delete the gene encoding XIP. Thus the S. sobrinus ComRS pathway provides new tools for studying this pathogen and offers a lens into the evolution of ecological cheaters. The discovery of S. sobrinus ComRS system led us to analyze ComRS networks in all seven cariogenic streptococci. We found that most of them possess two paralogous ComRS systems. We expanded genetic tractability from only one species (Streptococcus mutans) to six of the seven streptococci, and dissected the ComRS network structures in detail for five. A high level of diversity is observed in these ComRS networks. Our results serve as a major expansion of the ComRS system paradigm. Of particular significance is the disentanglement of the dual-ComRS network in S. mutans, whose Type II ComRS network has been the primary ComRS system model. We show S. mutans has two paralogous ComRS systems with bidirectional crosstalk. We discovered that ComRS promoter specificity depends on the sequence of the promoter, providing a basis for the separation and crosstalk in S. mutans and S. sobrinus ComRS networks. In S. mutans, even a single base pair change could potentially lead to complete integration of the two systems. The diversity of dual-ComRS networks revealed in this study depends on the presence of two paralogous systems and is facilitated by the modularity of different network components. While natural competence is important for genome adaptability, the flexibility in natural competence-regulating networks may provide an added layer of adaptability on top. We envision that paralogous regulatory systems may be used as a strategy in engineering biology to either generate network structure libraries or to easily modulate network outcomes."],"dc:format":["application/pdf"],"dc:identifier":["https://hdl.handle.net/2142/115511"],"dc:language":["en","eng"],"dc:rights":["Copyright 2022 Jinbei Li"],"dc:subject":["Streptococci","quorum sensing","natural competence","transcriptional network","paralogous systems","bacterial evolution","oral bacteria"],"dc:title":["Coexistence of paralogous quorum sensing systems leads to diverse network topology for coordinating competence and bacteriocin biosynthesis in cariogenic streptococci"],"dc:type":["text","Thesis"],"thesis:degree_discipline":["Bioengineering"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Ph.D."],"thesis:institution_name":["University of Illinois at Urbana-Champaign"]},"updated_at":"2026-07-22T22:24:54Z"}