Corycin identified as a cause of pulmonary fibrosis; antibody blockade limits damage

A bacterial protein fragment called corycin has been identified as a direct cause of pulmonary fibrosis. Blocking it with an antibody limited the damage.

According to Azolife Sciences on the 1st (local time), a joint research team from the University of Illinois Urbana-Champaign and Mie University in Japan reported in the journal Nature Communications that corycin causes pulmonary fibrosis by disrupting the cell’s quality-control system.

Fibrosis is the process by which healthy tissue is replaced by scar tissue after being damaged or dying. It occurs in the lungs, kidneys, liver, heart and skin, and contributes to about half of all deaths in developed countries, the researchers said.

Corycin is a peptide cleaved from a protein produced by bacteria that are part of the human gut microbiome. In 2020, the researchers first established that corycin kills lung cells and worsens pulmonary fibrosis.

In this study, the researchers analyzed lung fluid samples from patients with pulmonary fibrosis that were collected during routine care at a hospital in Japan. They found DNA from corycin-associated bacteria in the lung fluid. This is the first evidence that corycin-producing bacteria are present in the lungs.

The researchers removed corycin from patient samples using an antibody they developed and then applied the samples to healthy cell cultures. The corycin-depleted fluid no longer killed cells.

Isaac Khan, a professor at the University of Illinois, said, “We demonstrated that corycin present in patients is biologically active and can directly damage lung cells. When we neutralized corycin with an antibody, the cells were largely protected from damage.”

The researchers also found that after entering cells lining the lungs, corycin accumulates in mitochondria, which are responsible for energy production and protein quality control. Corycin disrupted this quality-control system, triggering oxidative stress, premature cellular senescence, cell death and scar formation.

To demonstrate that corycin produced locally in the lungs, rather than corycin traveling from the gut through the bloodstream, causes fibrosis, the researchers created genetically engineered mice that continuously produce corycin in their lungs. The mice spontaneously developed pulmonary fibrosis without an external bacterial source.

Professor Esteban Gabazza said, “Corycin is so potent that it can have harmful effects even at extremely low concentrations. This means that even trace amounts of corycin can trigger substantial biological effects.”

Mice treated with a corycin-binding antibody had substantially less pulmonary fibrosis, lower disease severity and improved survival.

Khan said, “These results provide a strong proof of concept that neutralizing corycin could be a completely new treatment strategy for pulmonary fibrosis and fibrotic diseases in other organs.”

The researchers plan to continue refining a treatment that uses their patent-pending antibody to block corycin before it enters cells. They are also exploring alternative treatment approaches to restore protein quality or protect mitochondria.