IN BRIEF

Cysteamine Appears to Help Clear Antibiotic-Resistant Bacteria from Cells of Patients With Cystic Fibrosis

November 29, 2017
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The drug could help eradicate members of the B. cepacia complex and other bacteria in CF.

Physicians and researchers from Nationwide Children’s Hospital have found that the drug cysteamine protects cells of patients with cystic fibrosis (CF) against a group of disease-causing and multi-drug resistant microorganisms — members of the Burkholderia cepacia bacterial complex — in several ways.

Notably, B. cenocepacia can have wide-ranging effects in people with CF, from accelerated health decline to a rapid and often fatal sepsis-like condition.

“We have good evidence cysteamine could be an effective addition to antibiotics for eradicating certain members of the bacteria complex as well as other bacteria in CF,” says Benjamin Kopp, MD, MPH, a member of the Section of Pulmonary Medicine at Nationwide Children’s, principal investigator in the Center for Microbial Pathogenesis and senior author of the study. “If you remove the bacteria, you prevent the inflammation and cell death it causes.”

Cysteamine is currently used to prevent the damaging accumulation of the amino acid cystine in the body, caused by the disease nephropathic cystinosis. The disease hampers cells’ ability to clear cystine, an aberrant amino acid. The drug has already been shown to thin mucus and have anti-biofilm properties, and an ability to kill bacteria, which made it attractive to study in CF patients, Dr. Kopp says.

Ironically, B. cepacia microorganisms hide out in immune cells called macrophages, interfering with and evading macrophages’ ability to engulf and degrade them through a process called autophagy. Autophagy is a cell’s housecleaning process, whereby it removes unnecessary, foreign and impaired components.

During testing in the lab, cysteamine killed bacteria directly and significantly reduced bacterial invasion of treated human peripheral blood monocyte-derived macrophages collected from CF patients.

The drug also decreased the accumulation of proteins known to block autophagy, restoring functions essential to the immune system’s natural ability to rid cells of the foreign invaders, the researchers report in the journal PLOS ONE.

The resulting increased uptake and degradation of B. cepacia bacteria is directly tied to the cystic fibrosis transmembrane regulator (CFTR) channel that normally transports ions in and out of cells, says Dr. Kopp, who is also an assistant professor of Pediatrics at The Ohio State University College of Medicine.

Genetic mutations characteristic of CF result in impaired ion transport and downstream signaling, which enables the bacteria to thrive. “This drug helps restore CFTR expression in macrophages, which makes it attractive for purposes in CF beyond bacterial killing,” Dr. Kopp says.

Dr. Kopp and colleagues are currently involved in a worldwide phase 2 clinical trial testing how adult CF patients with pulmonary exacerbations tolerate and respond to cysteamine treatment.

In addition to CF, Dr. Kopp and colleagues suggest that the drug has potential to treat other diseases in which autophagy and bacterial clearance are impacted, such as chronic granulomatous disease and sepsis, and other conditions with poor immune function.

 

Reference:

Shrestha CL, Assani KD, Rinehardt H, Albastroiu F, Zhang S, Shell R, Amer A, Schlesinger LS, Kopp BT. Cysteamine-mediated clearance of antibiotic-resistant pathogens in human cystic fibrosis macrophages. PLOS ONE.  2017 Oct 5; 12(10).

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