Discovery could help treat deadly, drug-resistant pneumonia and sepsis

Bacterial pneumonia and sepsis are leading causes of hospitalization and death. Researchers at Kansas State University’s Division of Biology have discovered that a malfunction in the body’s immune response to bacterial infection may be part of the problem.

Pankaj Baral, assistant professor of biology, and Prabhu Raj Joshi, a doctoral student in microbiology, are studying how cross-talk between the nervous and immune systems, or bilateral signaling, affects the body’s ability to fight pneumonia caused by the Gram-negative bacteria known as carbapenem-resistant Klebsiella pneumoniae, or CRKP.

The researchers published their study, “Nociceptive sensory neurons innervating the lungs promote pneumonic sepsis during carbapenem-resistant Klebsiella pneumoniae pulmonary infection,” in Scientific progress.

CRKP bacteria are the most common cause of hospital-acquired lung infections and are a major contributor to fatal pneumonia-induced sepsis, or pulmonary sepsis, in hospitalized patients. The U.S. Centers for Disease Control and Prevention considers CRKP and other Gram-negative bacteria an urgent public health threat and states that alternative, non-antibiotic treatment for Gram-negative pneumonia and pulmonary sepsis is essential.

The study by Baral and Joshi examined the role of neuroimmune signaling in bacterial pneumonia, focusing on nociceptive sensory neurons innervating the lungs (neurons that mediate pain) during CRKP pulmonary infection.

Normally, the sensory nervous system protects the body by detecting and responding to harmful stimuli. However, the study showed that during CRKP lung infection, the sensory nervous system is at risk, and the sensory neurons innervating the lungs, which are supposed to defend against pneumonia and sepsis, appear to be the culprits.

“Our study showed that nociceptor activation and pain sensations, normally considered essential defense mechanisms, actually increase CRKP infection and pneumonia mortality,” Joshi said. “So we think that CRKP may use nociceptor neuron activation to establish infection and cause severe disease such as sepsis.”

The discovery could help scientists develop a non-antibiotic treatment for sepsis that targets nociceptor neurons or blocks their receptor signaling pathways.

In fact, the team is collaborating with researchers at the University of Kansas to conduct high-throughput screening of small molecules to identify the most potent chemical inhibitors of nociceptor signaling for use as therapeutics for Gram-negative pneumonia and sepsis.