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Researchers say genetics may determine wound infection and healing – KLBK | KAMC | EverythingLubbock.com

June 26th, 2020 4:53 pm

LUBBOCK, Texas (NEWS RELEASE) The following is a news release from Texas Tech University:

Think of the last time you had a cut on your leg or foot. How long did it take for that wound to show signs of healing? If it was longer than three weeks, doctors would refer to it as a chronic wound. These types of non-healing wounds affect millions of people and are often associated with other chronic diseases or conditions like diabetes, decreased circulation and neuropathy.

But now, in a first-of-its-kind study, researchers have determined that genetics may play a role in how wounds heal.Caleb Phillips, an assistant professor at Texas Tech University and director of thePhillips Laboratoryin theDepartment of Biological Sciences, anddoctoral studentCraig Tipton led the study, Patient genetics is linked to chronic wound microbiome composition and healing, published Thursday (June 18) in the open-access, peer-reviewed medical journalPLOS Pathogens.

Phillips, who also serves as the Curator of Genetic Resources at theNatural Science Research Laboratorys (NSRL)Robert J. Baker Genetic Resources Collection, said the study determined that certain genes are associated with the number of bacteria and abundance of common pathogens in wounds. The collection of microbes, known as a microbiome, can determine how a wound heals and how long that process takes. The research also showed that the more diversity within a wound microbiome, the less time it took to heal.

A chronic wound is a serious burden, Phillips said. The median healing time of patients in this study was more than 200 days, but some people deal with these wounds for years. We were able to show that a persons genetics explain differences in the species that infect their wounds. The information in this study could be valuable in a clinical setting as pre-operative information to help inform preventative measures before a procedure, as some chronic wounds arise as non-healing surgical wounds, and could help inform a course of treatment for an existing infection.

Researchers included colleagues from Texas Tech, theTexas Tech University Health Sciences Center(TTUHSC), LubbocksSouthwest Regional Wound Care Center(SWRWCC) and the University of North Texas Health Science Center at Fort Worth (UNTHSC). Phillips said the project began after a conversation with Dr. Randy Wolcott, founder of the SWRWCC, where they discussed how certain patients develop multiple non-healing wounds over a long period. The microbiome within each wound was essentially the same. The researchers wanted to find out if this could be partially explained by genetics.

This study is big, Wolcott said. Its the initial study to find genes and/or gene alterations that correlate with what bacterial species can be more successful in causing infections in a specific patient. If a screen of a patients DNA prior to a surgery showed that patient is highly susceptible to a staphylococcus species, the doctor could mitigate staphylococcus complications.

Patients visiting the SWRWCC for the care of a lower-extremity infected wound consented to participation in the study and provided samples from their wound(s) and from a cheek swab. Samples like those collected at the SWRWCC are archived in liquid nitrogen at the Wolcott Wound Care Research Collection, a collection of the NSRLs Genetic Resources Collection that is specifically dedicated to wound care biology. The design of the study included an exploratory cohort of 79 patients, from which candidate locations of their genome were identified. This was followed by an experimental cohort of 85 patients, used to confirm associations between the genomic locations and wound microbiome characteristics.

The bacterial communities infecting an individuals wounds were determined by microbiome sequencing methods, and each patients genome was characterized at a few hundred thousand specific locations, called single nucleotide polymorphisms, or SNPs. A statistical approach was then used to determine which of these genomic locations explained differences in an individuals wound microbiome composition and was followed with several downstream analyses to understand the results.

We showed that there are identifiable locations in peoples genome where, depending on their genotype, they tend to get infections by specific bacteria, Phillips said. The different genomic locations identified tend to be related in terms of the types of genes they are close to and may regulate. A working hypothesis emerging from the research is that genetic differences influencing genes encoding the way our cells interact with the environment and each other are important for infection differences.

Tipton, who completed his bachelors degree in biology atAngelo State Universitybefore arriving at Texas Tech, said the project has been a significant part of his dissertation, which focuses on learning more about why a persons wounds are infected by different types of microbes. Though there is still work to be done before the research directly benefits patients, Tipton said the study is an important and promising step in that direction.

Personalized medicine is a current hot topic in modern healthcare, where the goal is to identify inherent differences within individuals that may cause them to be impacted differently by disease and finding treatments that are well-suited and tailored to the individual and may contribute to better patient outcomes, Tipton said. Our project furthers two equally-interesting avenues of research with potential translation to the clinic. In one, it is our goal to develop robust genomic predictive models that could help physicians to determine a patients risk for chronic wound infection, particularly to specific bacteria.

In the second, this work helps to inform how genetic variation in patients can influence microbiome-host interactions and wound infection pathogenesis. By further studying infection pathogenesis and how these complex microbial communities interact, it may be possible to improve existing therapies or to develop new therapeutic strategies altogether.

Phillips said he looks forward to continuing his research at Texas Tech. His lab is developing a follow-up study that he hopes will collect enough information to create accurate predictive models. They also are working on a study exploring how a persons location in the U.S. shapes differences in chronic wound microbiomes.

Texas Tech provides good support for research and is continually working for growth, Phillips said. My research, like that of most others, has been generally enhanced by the academic freedom provided at the university. The Natural Science Research Laboratory is a premier Natural History Collection, and the samples archived at the Genetic Resources Collection have allowed me to design studies such as this one that would otherwise not have been possible. The hard work and creativity of doctoral student Craig Tipton were essential to the success of this project, as was collaboration with the laboratories ofNicole Phillipsat UNTHSC andKendra Rumbaughat TTUHSC, ProfessorTodd Littlein the Texas TechCollege of Education, the SWRWCC and the NSRL.

The team of researchers included:

To read the complete study, visit the PLOS Pathogens website.

(News release from Texas Tech University)

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Researchers say genetics may determine wound infection and healing - KLBK | KAMC | EverythingLubbock.com

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