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Understanding Enterobacteriaceae Behavior in Bloodstream Infections


Bacteria from the Enterobacteriaceae family pose significant health risks, especially in individuals with inflammatory bowel diseases (IBS), due to their association with conditions like gastrointestinal bleeding, bacteremia, and sepsis. Despite this, the precise mechanisms enabling their entry into the bloodstream remain poorly understood. This study reveals that Enterobacteriaceae extensively utilize human serum as a nutrient source. Chemotaxis, facilitated by the Tryptophan sensory receptor (Tsr) chemoreceptor, enhances their ability to migrate into enterohaemorrhagic lesions. Termed “bacterial vampirism,” this phenomenon may contribute to the increased likelihood of bloodstream infections by Enterobacteriaceae. It underscores the importance of understanding bacterial behaviors and mechanisms in developing infectious diseases.

Arden Baylink PhD is an Assistant Professor of Veterinary Microbiology and Pathology at Washington State University. He leads a laboratory dedicated to research on infectious diseases and antibiotic development.

“Bacteria have this interesting behavior they’re capable of called chemotaxis. And the basic premise of chemotaxis is essentially a sense of smell for the bacteria,” according to Baylink. “They use chemotaxis to sense their environment and be able to navigate. We’ve thought this is probably important for how bacterial pathogens colonize, infect, and cause disease. That was one of the sorts of big-picture questions we were interested in. Typically, we were curious about how the bacteria might respond to a source of human blood. And the reason is because, you know, one of the worst outcomes you can have of a bacterial infection is the bacteria getting into the bloodstream, which can ultimately be lethal.”

Experimental findings revealed that clinical isolates of Salmonella enterica, E coli, and Citrobacter koseri gravitate toward human serum, demonstrating a chemotactic response. Subsequent analysis pinpointed L-serine as the principal chemical cue driving this chemoattraction, with the chemoreceptor Tsr directly binding to L-serine. Structural investigations, including crystallography, offered insights into the molecular interactions underlying this process, unveiling a conserved amino acid recognition motif among Tsr orthologues.

“We saw very consistently, in our systems the bacteria were attracted to sources of the liquid component of blood serum, and 2 specific sets of chemicals that are present in serum, 1 of them being this amino acid nutrient serine,” according to Baylink. “If that holds and infections that would suggest that modal swimming bacteria, if they are exposed to a source of bleeding when we’re within the gut, that they’re going to swim to that and be attracted to it. When we took intestinal tissue and looked at the bacteria, their ability to use chemotaxis, we saw that they would swim up into the damaged vasculature. It’s possible that this process of chemotaxis could be involved in bacterial entry into the bloodstream.”

To simulate GI bleeding and investigate bacterial response, researchers employed a custom injection-based microfluidics device, utilizing femtoliter volumes of human serum as a chemoattractant. Structural analyses, including crystallography, were then conducted to delineate the chemical cues guiding bacterial chemoattraction. The phylogenetic distribution of the Tsr chemoreceptor among Enterobacteriaceae and its interaction with L-serine, a critical component of human serum, aimed to comprehend the broader implications of the findings.

“There are certain sections of the population that are at extremely high risk for bloodstream infections, and among these are people with IBS. So, people with Crohn’s disease and ulcerative colitis, essentially have intestinal lesions that that are that are quite prolific and prolonged,” according to Baylink. “And these can be entry points for bacteria into the bloodstream. It could be that populations of patients such as these could benefit from a therapeutic that would block the ability of these bacteria to use chemotaxis and be attracted to that source of serum. Sepsis is a leading cause of death for people with IBS.”

Baylink’s research uncovers how Enterobacteriaceae bacteria are drawn to human blood serum through chemotaxis, potentially leading to bloodstream infections, notably in individuals with IBS. Targeting bacterial chemotaxis could be a promising approach for preventing such infections, emphasizing the significance of understanding bacterial behaviors in disease management.

Reference

Baylink A, Glenn S, Shavlik, et. al. Bacterial Vampirism Mediated Through Taxis to Serum. eLife. Published April 16, 2024. Accessed May 14, 2024. doi: https://doi.org/10.7554/eLife.93178.2



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