Austin Nuxoll studies antibiotic tolerance and the lingering problems it causes – UNK News

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By Tyler Ellyson
Communications UNK

KEARNEY – Antibiotic treatment failure is one of the biggest threats to global health.

Antibiotic-resistant bacterial infections killed more than 1.2 million people and were indirectly linked to nearly 5 million deaths in 2019, according to the Centers for Disease Control and Prevention. More than 2.8 million antibiotic-resistant infections occur each year in the United States alone, causing more than 35,000 deaths.

“A lot of people have heard of antibiotic resistance. We’ve seen it in the news with different bacteria becoming resistant to antibiotics, and we’re running out of antibiotics to treat them. This is very important,” said Austin Nuxoll, an associate professor at the University of Nebraska at Kearney. Biology department.

“But what is often overlooked are all the infections caused by drug-susceptible pathogens. We have many infections caused by bacteria that are not resistant to antibiotics, but antibiotic therapy always fails.

Antibiotic resistance occurs when bacteria and other infection-causing microbes evolve and develop the ability to defeat drugs designed to kill them. As medications become less effective, these infections are harder to treat, leading to longer hospital stays, higher medical costs, and increased mortality.

Nuxoll investigates a similar, but separate, issue known as antibiotic tolerance. These microorganisms are not resistant to antibiotics, but they still manage to survive treatments, continue to grow in the host and cause persistent problems.

“It’s very overlooked compared to antibiotic resistance, but it’s clinically very important,” Nuxoll said. “The hospital stay and the costs associated with that hospital stay are not that different in some cases between patients infected with antibiotic-resistant organisms and antibiotic-susceptible organisms.

“We have a lot of patients who don’t survive these treatments when they should.”

Nuxoll has been researching antibiotic tolerance since 2010, when he was a doctoral candidate at the University of Nebraska Medical Center. His work focuses on Staphylococcus aureus (staphylococcus), a type of bacteria commonly found on the human body.

Staph bacteria are generally harmless, but they can cause life-threatening infections if they enter the bloodstream or internal tissues.

“They often cause these skin and soft tissue infections,” Nuxoll noted, “but they cause more serious infections when they enter the bloodstream.”

Staph infections are notoriously difficult to treat due to antibiotic resistance – MRSA is the case – and antibiotic tolerance. They can spread both in the community and in health care settings.

“Often these infections are associated with prosthetic devices such as joint implants or catheters,” Nuxoll said.

This is because staph infections are mediated by biofilms, a community of bacteria that adhere to each other and to a surface, such as a prosthesis.

“These biofilms are quite difficult to treat once they form in a host. When a patient gets an infection and is treated with antibiotics, they have up to a 20% chance of developing recurrent infections. said Nuxoll, who thinks lingering cells might be to blame.

Lingering cells do not respond to antibiotics, allowing the bacteria to remain in a dormant state during treatment. “Once the antibiotic therapy is withdrawn, they begin to repopulate the environment and start growing again, causing these chronic, recurring infections,” Nuxoll said.

Nuxoll and collaborators published a study in 2019 showing that polymicrobial infections — those caused by biofilms with more than one type of bacteria — also include increased numbers of lingering cells. A follow-up study published last year shows that persistent cells can survive the immune system better.

“This could explain why these infections are worse for patients and why they have a worse prognosis,” Nuxoll said.

In the future, Nuxoll hopes to move its research from the lab to a clinical setting, with the goal of developing more effective treatments for staph and other antibiotic-tolerant infections.

“That link to clinical manifestation has to be established at some point,” he said. “That’s where we’d like to get to.”

STUDENT MENTORSHIP

In addition to advancing the medical field, Nuxoll loves research because it allows him to work one-on-one with students in a lab.

He frames six undergraduate researchers throughout the school year and three during the summer.

“It’s really a huge benefit for the student to get involved in undergraduate research,” he said. “They learn critical reasoning and other skills while applying the concepts they learn in the classroom to a problem facing the medical community. A lot of my students are in pre-med, so they want to be doctors one day, and staph is something they’ll come across in most specialties they study.

The Comstock native knows firsthand how valuable that experience can be. He studied biology at UNK and became involved in undergraduate research through INBRE, a program funded by the National Institutes of Health that promotes and supports biomedical research.

After a summer at the University of Nebraska-Lincoln, Nuxoll worked alongside UNK biology professor Paul Twigg, which sparked his interest in research.

“I fell in love with it,” he said. “I knew I wanted to get into research.

Nuxoll received his doctorate in pathology and microbiology from UNMC in 2014 and spent two years as a postdoctoral associate at Northeastern University in Boston before returning to UNK as a faculty member in 2016.

“I’ve worked with an incredible group of undergraduate students since joining UNK,” he said. “My research achievements are a direct result of their hard work. Working with and mentoring undergraduate research students is a passion I have been fortunate to pursue during my time here.

His students have presented their research at numerous regional and national events, including the American Society for Microbiology conferences in New Orleans, San Francisco, and Washington, D.C.

“It can be painful to watch sometimes when they’re struggling, and it just doesn’t work for them. But then, when it all clicks into place, it’s quite gratifying to watch them come to terms with it all and feel a sense of accomplishment for what they’ve contributed.

PHOTOS BY TODD RUNDSTROM PHOTOGRAPHY

Title: Associate professor of biology
Middle School: arts and sciences
Education: Bachelor of Science, University of Nebraska at Kearney, 2009; Ph.D., University of Nebraska Medical Center, 2014.
Years at UNK: Six
Courses taught: Infectious diseases, virology, general microbiology, current issues in biology and bioethics.
Recently published articles: “Interruption of the tricarboxylic acid cycle in Staphylococcus aureus results in increased tolerance to innate immunity”, AIMS Microbiol, 2021; “Candida Albicans induces multi-drug tolerance in Staphylococcus aureus through energy depletion”, Front Microbiol, 2019; “Stochastic variation in TCA cycle expression produces persistent cells”, mBio, 2019.



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