The human gut is exposed to toxins, pathogens, dietary changes, antibiotics, and other disturbances that can cause alterations to our microbiome. So how is it that the gut of healthy individuals remains largely stable despite these perturbations? When we get sick, why is it that our body’s “good” bacteria remain in the gut while the bacteria causing the infection are killed off by our immune system? A study out of Yale, published last week in Science, identified a single gene in bacteria that allows for these bacteria to resist inflammation-associated antimicrobial peptides that are released by the body to kill off harmful bacteria.
The scientists found that this gene, lpxF, encodes for an enzyme in the cell membrane of bacteria to be slightly altered from bacteria lacking this specific gene. To figure this out, they exposed 17 commensal (or normal) bacteria to antimicrobial peptides (AMPs) and found that they were more resistant than pathogens that were also exposed to the same AMPs. They then mutated the genes of five species of Bacteroidetes at various points and checked to see which ones became less resistant to AMPs. They found one gene that was common across all five species, lpxF.
They also did experiments in which they genetically manipulated bacteria to knock out the lpxF gene and put these bacteria into germ free mice along with the same bacteria with the functional lpxF gene. In the absence of a pathogen, the bacteria lacking the lpxF gene performed just as well as the bacteria with the gene. When a pathogen was introduced into the mouse, inducing an immune response, the bacteria lacking the lpxF gene was greatly reduced in comparison to the other bacteria with functional lpxF. This showed that the gene was protecting the bacteria from the AMPs.
Lastly, they took fecal samples from twelve individuals and exposed bacteria from them to AMPs. They found that in comparison to pathogens that did not survive very well after exposure, the commensal bacteria performed very well. This is a very important study as it opens up a new understanding of how bacteria in the body are saved from an immune response after exposure of a pathogen in the body. There are most likely many more genes that play similar roles to lpxF and this work opens up new avenues to better understand how commensal microbes interact with the human body as well as pathogens in the body.