Bacterial resistance is becoming more common in hospitals, and it’s accelerating.
The main culprit is a group of organisms known as gram-negative bacteria, which cause the majority of hospital-acquired infections — such as pneumonia — which are both prevalent and dangerous.
“A complete overhaul of the approaches to resistance, disease and prevention could change the continuing upward trajectory of antibiotic resistant infections,” Brad Spellberg, M.D. said. “To do anything less invites a bleak post-antibiotic future, in which infectious diseases once again reign supreme.”
This process has been ongoing for a number of years. Sick people in hospitals have always caught infections, but what’s new is that these organisms are becoming more and more resistant to antibiotics.
Bacteria acquire resistance faster than new antibiotics can be made to fight them, because their life spans are so short that they can create several new generations in a day. They are able to adapt very quickly.
“We are looking to identify parts of the host response that are necessary to fight the infection, and then augment it in a host in order to more effectively fight the infection,” Borna Mehrad, MBBS, of U.Va.’s Division of Pulmonary and Critical Care Medicine, said.
Mehrad and his team were interested in this group of cells called monocytes and macrophages, as these are the white blood cells of the body that are important in immune response and specifically in pneumonia. This led them to focus on a key growth factor called macrophage colony-stimulating factor, or M-CSF.
“We found that if you take away the M-CSF, the mice became more susceptible to the infection. And now the question became how,” Mehrad said. “The original hypothesis was that the M-CSF was involved in production of monocytes. It turns out this is completely wrong.”
One of Mehrad’s PhD students, Alexandra Bettina, decided to look at the recruitment of monocytes into the lungs, and nothing was unusual. Moreover, the number of monocytes in the bone marrow and the blood, where they are produced, was normal.
“She eventually figured out that locally produced M-CSF in the lung kept the monocytes and macrophages there alive, so it’s a survival factor,” Mehrad said.
An additional discovery was that the liver of the experimental mice looked unhealthy in the absence of M-CSF. It turns out bacteria from the lung gets into the blood and spreads, causing the mice to contract liver infection.
Now that the role of M-CSF as a cytokine — a substance which is discharged from one cell and affects others — has been seriously examined and measured during infection, some possibilities arise for augmenting the body’s natural defenses.
“One possibility is seeing whether having more M-CSF is beneficial. Having more than normal might not necessarily be better,” Mehrad said. “There could be an optimal range.”
Although there aren’t any immediate clinical applications, there is the added possibility of identifying hospitalized patients who don’t make a normal amount of M-CSF, and using M-CSF as a therapeutic treatment for patients.
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