S. Aureus Found Mostly in Lung Mucus, Not Tissue, Pig Model Shows

S. Aureus Found Mostly in Lung Mucus, Not Tissue, Pig Model Shows
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Using pig lungs as a model, scientists discovered that Staphylococcus aureus, a species of bacteria often found in the lungs of children with cystic fibrosis (CF), preferentially colonizes the mucus circulating there rather than organ tissue itself.

According to the researchers, these findings may open new ways of treating such lung infections in CF children and adults, including treatment-resistant infections, enabling a lower amount of prescribed antibiotics against S. aureus than is now normally given.

“The model we have used with pig lung has shown that S.aureus preferentially grows within mucus,” Esther Sweeney, PhD, a research assistant with the School of Life Sciences at the University of Warwick, and the study’s first author, said in a press release.

A pig lung model, Sweeney added, also appears to better represent “the clinical situation for people with CF” than do “historical research models.”

“We think … our model could be used to further investigate the best ways of treating MRSA [methicillin-resistant Staphylococcus aureus] infection associated with cystic fibrosis. In future this may help to reduce inappropriate use of antibiotics,” she said.

These findings were reported in the study, “An ex vivo cystic fibrosis model recapitulates key clinical aspects of chronic Staphylococcus aureus infection,” published in the journal Microbiology.

S. aureus is the most common organism found living in the airways of children with CF. When these bacteria, including the MRSA strain, are detected, patients are given antibiotics to prevent lung function decline.

But these antibiotics often fail to fully eliminate lung disease and its symptom, leading some to question whether antibiotic use is best possible treatment for S. aureus. How this bacteria affects the lungs of young patients are also not fully understood.

Previous studies have shown that when these bacteria colonize mice lungs, they tend to invade cells or the interstitium — the tissue and space surrounding the lungs’ alveoli (small air sacks) — and abscesses form.

However, in CF patients, these bacteria are rarely seen in the interstitium, and abscesses are highly unusual.

“Bacteria instead appear to localize in mucus plugs in the lumens of bronchioles,” the researchers wrote. Bronchioles, one of the smallest lung airways, are connected to the alveolar ducts that house the alveoli.

Using pig lungs acquired from a butcher shop as a model system, and artificial mucus to mimic CF patients’ lung secretions, researchers in the U.K. and Spain found that — unlike in mice — when S. aureus colonizes pig lungs it tends to form aggregates in mucus, rather than invading the organs’ tissue and forming abscesses.

“We decided to make a new model using a pig lung, rather than mice, because pig lungs are more similar to human lungs, and we can combine them with artificial CF mucus. We think this makes bacteria behave more like they would in the lungs of a person with CF,” said Freya Harrison, PhD, an associate professor at the Life Sciences school and the study’s senior author.

Investigators infused the pig lungs with a man-made version of CF mucus, and then added the bacteria.

They observed how S. aureus colonized the animals’ lungs. Unlike previous reports in mice, S. aureus in pig lungs were not seen to invade the animals’ lung tissue. Instead, these bacteria seemed to concentrate and form large aggregates in the artificial CF mucus that had been added to the organs. No abscesses were observed.

According to the team, these findings may provide valuable insights into the effects S. aureus has on the lungs of CF patients, which could lead to new and more effective treatments for infections caused by these bacteria.

“Knowing how exactly the lungs are affected by different bacteria is key to treating infection efficiently. We need to know which bacteria do the most damage, and how best to target them to get rid of them,” Harrison said.

Joana holds a BSc in Biology, a MSc in Evolutionary and Developmental Biology and a PhD in Biomedical Sciences from Universidade de Lisboa, Portugal. Her work has been focused on the impact of non-canonical Wnt signaling in the collective behavior of endothelial cells — cells that made up the lining of blood vessels — found in the umbilical cord of newborns.
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Joana holds a BSc in Biology, a MSc in Evolutionary and Developmental Biology and a PhD in Biomedical Sciences from Universidade de Lisboa, Portugal. Her work has been focused on the impact of non-canonical Wnt signaling in the collective behavior of endothelial cells — cells that made up the lining of blood vessels — found in the umbilical cord of newborns.
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