Immune response to infection depends on biofilm mechanics, matrix viscoelasticity

In the human body, bacteria sometimes change from their free-swimming state to cluster together to form communities, or biofilms, the most common cause of chronic bacterial infections. Bound together by a matrix of polymers and proteins that give rise to viscoelastic properties, bacteria in biofilms are often resistant to antibiotics or immune responses like phagocytosis, a process whereby neutrophils -- white blood cells that act as first responders to infection -- eliminate pathogens.

“It seemed likely that biofilm mechanics … play a role in [its resistance to immune system clearance], and yet almost nothing is known about it,” said co-author Vernita Gordon.

Using gel as biofilm surrogate, Bakhtiari et al investigate the relationship between neutrophil phagocytosis and materials elasticity to gauge immune response efficacy.

The work determined that if a large gel target is soft but tough, phagocytic success depends on how long neutrophils are exposed to it. If it is stiff but less tough, duration of exposure is a negligible factor. These findings are relevant, since biofilm infections fight back against neutrophils with virulence factors, chemicals that damage and kill host cells and, given enough time, render neutrophils useless.

In contrast to manual micrograph analysis, the research employs flow cytometry, doubling cell numbers analyzed per experiment, and reducing time from hours to minutes. A standard tool in biology, flow cytometers can help facilitate the study of phagocytosis in a variety of circumstances.

“Biofilms are problematic in many scenarios, from implanted medical devices to chronic wounds in diabetes, to infected lungs in cystic fibrosis and chronic obstructive pulmonary disease,” said Gordon. “This [study] will be important for understanding how to enhance immune system efficacy.”

Source: “High-throughput assays show the timescale for phagocytic success depends on the target toughness,” by Layla A. Bakhtiari, Marilyn J. Wells, and Vernita D. Gordon, Biophysics Reviews (2021). The article can be accessed at https://doi.org/10.1063/5.0057071 .