Regulatory mechanism of novel host-relevant biofilm formation protein in non-Cholera Vibrio species
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Principal Investigator: Morgan Eilise Milton Organization: EAST CAROLINA UNIVERSITY Fiscal Year: 2024 Award: $107,120 Funding agency: National Institute of Allergy and Infectious Diseases PROJECT SUMMARY/ABSTRACT Non-cholera Vibrio (NCV) species represent a notable and increasing threat to human health and food safety. The biofilms formed by Vibrio species are robust and highly relevant to host infection. Biofilms are tightly regulated communities of matrix-associated bacteria and are a major component of bacterial pathogenesis including drug resistance. Since an estimated 75% of bacterial infections involve biofilms, it is crucial to better understand how biofilms are formed. In this application, I propose to elucidate the molecular mechanism of an unusual regulatory protein necessary for controlling NCV biofilm formation. This protein is conserved in NCVs and controls the production of symbiosis polysaccharide (Syp), a component of the biofilm matrix involved in host infection. Based on preliminary findings, this protein has an atypical mode of action compared to well characterized homologs. My fundamental hypothesis is that this NCV biofilm regulator protein uses a novel mechanism to control biofilm formation and will challenge our current understanding of this family of proteins. My hypothesis will be addressed through two specific aims: 1) probing the protein’s function using biochemical and structural characterization studies, and 2) uncovering its position in the regulatory network by identifying binding partners. The proposed research is innovative because it focuses on a system that is crucial for biofilm formation, and to date, the system has only been investigated using cellular and genetic approaches. The structure-function approach proposed here will provide essential information needed to fill our knowledge gaps. The project is significant because it will provide a deeper understanding of the regulation of host-associated biofilms from the rising threat of NCV infection. Ultimately, the work proposed will answer key questions related to the molecular mechanisms of a protein within a critical and conserved pathway that regulates host-relevant biofilms. Support from this K22 award will facilitate my transition to an independent investigator by providing me with resources to generate data and publications that will strengthen my competitiveness for future funding. Terms: <Address><B subtilis><B. subtilis><Bacillus subtilis><Bacteria><Bacteria resistance><Bacteria resistant><Bacterial Infections><Bacterial resistant><Beneckea><Binding><Biochemical><Biophysics><Cell-Extracellular Matrix><Communities><Complex><Data><Disease><Disorder><Drug resistance><ECM><Environment><Extracellular Matrix><Food Poisoning><Food Safety><Funding><Future><Gene Expression><Gene Transcription><GeneHomolog><Genetic><Genetic Transcription><Genetic analyses><Glycans><Goals><Health><Homolog><Homologous Gene><Homologue><Human><Infection><Investigators><K22 Award><Knowledge><Listonella><Microbial Biofilms><Modern Man><Molecular><Molecular Interaction><NTPase><Nucleoside Triphosphate Phosphohydrolase><Nucleosidetriphosphatase><Outcome><Pathogenesis><Pathway interactions><Peptide Domain><Phosphorylation><Play><Polysaccharides><Position><Positioning Attribute><Process><Production><Protein Domains><Protein Family><Protein Phosphorylation><Proteins><Public Health><Publications><RNA Expression><Regulation><Regulatory Pathway><Regulatory Protein><Research><Research Personnel><Research Resources><Researchers><Resources><Role><Scientific Publication><Sigma Element><Sigma Factor><Sigma Initiation Factor><Sigma Subunit><Signal Pathway><Structure><Subgroup><Surface><Symbiosis><System><Techniques><Tertiary Protein Structure><Therapeutic Intervention><Transcription><United States><V fischeri><V parahaemolyticus><V parahemolyticus><V vulnificus><V. fischeri><V. parahaemolyticus><V. parahemolyticus><V. vulnificus><Vibrio><Vibrio Infections><Vibrio fischeri><Vibrio parahaemolyticus><Vibrio parahemolyticus><Vibrio vulnificus><Virulence><Work><Wound Infection><antagonism><antagonist><bacteria infection><bacterial community><bacterial disease><bacterial resistance><biofilm><biophysical foundation><biophysical principles><biophysical sciences><commensalism><drug resistant><experiment><experimental research><experimental study><experiments><genetic analysis><genetic approach><genetic regulatory protein><genetic strategy><host-associated biofilms><human pathogen><infected wound><innovate><innovation><innovative><insight><intervention therapy><model organism><novel><nucleoside triphosphatase><pathway><protein complex><protein protein interaction><protein structure><protein structures><proteins structure><regulatory gene product><resistance to Bacteria><resistance to Bacterial><resistance to Drug><resistant to Bacteria><resistant to Bacterial><resistant to Drug><response><social role><sulfate transporter><vibriosis>