Patient genetics is linked to chronic wound microbiome composition and healing

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dc.creatorTipton, Craig D.
dc.creatorWolcott, Randall D.
dc.creatorSanford, Nicholas E.
dc.creatorMiller, Clint
dc.creatorPathak, Gita A.
dc.creatorSilzer, Talisa K.
dc.creatorSun, Jie
dc.creatorFleming, Derek
dc.creatorRumbaugh, Kendra P.
dc.creatorLittle, Todd D.
dc.creatorPhillips, Nicole
dc.creatorPhillips, Caleb D.
dc.creator.orcid0000-0002-9324-2687 (Phillips, Nicole R.)
dc.creator.orcid0000-0003-3943-0895 (Pathak, Gita A.)
dc.creator.orcid0000-0002-8894-0368 (Silzer, Talisa K.)
dc.date.accessioned2022-11-15T22:34:38Z
dc.date.available2022-11-15T22:34:38Z
dc.date.issued2020-06-18
dc.description.abstractThe clinical importance of microbiomes to the chronicity of wounds is widely appreciated, yet little is understood about patient-specific processes shaping wound microbiome composition. Here, a two-cohort microbiome-genome wide association study is presented through which patient genomic loci associated with chronic wound microbiome diversity were identified. Further investigation revealed that alternative TLN2 and ZNF521 genotypes explained significant inter-patient variation in relative abundance of two key pathogens, Pseudomonas aeruginosa and Staphylococcus epidermidis. Wound diversity was lowest in Pseudomonas aeruginosa infected wounds, and decreasing wound diversity had a significant negative linear relationship with healing rate. In addition to microbiome characteristics, age, diabetic status, and genetic ancestry all significantly influenced healing. Using structural equation modeling to identify common variance among SNPs, six loci were sufficient to explain 53% of variation in wound microbiome diversity, which was a 10% increase over traditional multiple regression. Focusing on TLN2, genotype at rs8031916 explained expression differences of alternative transcripts that differ in inclusion of important focal adhesion binding domains. Such differences are hypothesized to relate to wound microbiomes and healing through effects on bacterial exploitation of focal adhesions and/or cellular migration. Related, other associated loci were functionally enriched, often with roles in cytoskeletal dynamics. This study, being the first to identify patient genetic determinants for wound microbiomes and healing, implicates genetic variation determining cellular adhesion phenotypes as important drivers of infection type. The identification of predictive biomarkers for chronic wound microbiomes may serve as risk factors and guide treatment by informing patient-specific tendencies of infection.
dc.description.sponsorshipThis work was supported by Texas Tech University Office Research and Innovation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
dc.identifier.citationTipton, C. D., Wolcott, R. D., Sanford, N. E., Miller, C., Pathak, G., Silzer, T. K., Sun, J., Fleming, D., Rumbaugh, K. P., Little, T. D., Phillips, N., & Phillips, C. D. (2020). Patient genetics is linked to chronic wound microbiome composition and healing. PLoS pathogens, 16(6), e1008511. https://doi.org/10.1371/journal.ppat.1008511
dc.identifier.issn1553-7374
dc.identifier.issue6
dc.identifier.urihttps://hdl.handle.net/20.500.12503/31925
dc.identifier.volume16
dc.publisherPLOS
dc.relation.urihttps://doi.org/10.1371/journal.ppat.1008511
dc.rights.holder© 2020 Tipton et al.
dc.rights.licenseAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourcePLOS Pathogens
dc.subject.meshAnimals
dc.subject.meshChronic Disease
dc.subject.meshDNA-Binding Proteins / genetics
dc.subject.meshDNA-Binding Proteins / metabolism
dc.subject.meshFemale
dc.subject.meshGenome-Wide Association Study
dc.subject.meshHumans
dc.subject.meshMale
dc.subject.meshMice
dc.subject.meshMicrobiota
dc.subject.meshPolymorphism, Single Nucleotide
dc.subject.meshPseudomonas Infections / genetics
dc.subject.meshPseudomonas Infections / metabolism
dc.subject.meshPseudomonas Infections / microbiology
dc.subject.meshPseudomonas Infections / pathology
dc.subject.meshPseudomonas aeruginosa
dc.subject.meshStaphylococcal Infections / genetics
dc.subject.meshStaphylococcal Infections / metabolism
dc.subject.meshStaphylococcal Infections / microbiology
dc.subject.meshStaphylococcal Infections / pathology
dc.subject.meshStaphylococcus epidermidis
dc.subject.meshTalin / genetics
dc.subject.meshTalin / metabolism
dc.subject.meshTranscription Factors / genetics
dc.subject.meshTranscription Factors / metabolism
dc.subject.meshWound Healing / genetics
dc.subject.meshWound Infection / genetics
dc.subject.meshWound Infection / metabolism
dc.subject.meshWound Infection / microbiology
dc.subject.meshWound Infection / pathology
dc.titlePatient genetics is linked to chronic wound microbiome composition and healing
dc.typeArticle
dc.type.materialtext

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