An important but challenging to define human gut bacterium called Bifidobacterium, which is employed in many probiotics that support healthy microbiomes, is the subject of new research from North Carolina State University.
The discoveries have the potential to improve so-called “good bacteria.”
Rodolphe Barrangou, corresponding author of a study presenting the discovery published today in Proceedings of the National Academy of Sciences, noted, “As our lab expands and diversifies the types of good bacteria that we work with, we turn to more finicky bacteria, like Bifidobacterium.”
Although “this bacterium is harder to grow and harder to work with than others,” the authors added, “we were able to make some important discoveries and understand more about the bacterium’s genetic basis for its health-promoting functionalities.”
According to Meichen (Echo) Pan, a Ph.D. candidate at NC State and the paper’s primary author, “Bifidobacterium is one of the two main players in the probiotic industry along with Lactobacillus and is particularly dominant in the colon of infants.” But compared to Lactobacillus, it is considerably harder to manipulate.
Scientists from North Carolina State University used both the bacterium’s native CRISPR-Cas system and a portable designed CRISPR effector to get their conclusions. CRISPR-Cas systems are immune systems that can change in response to threats, like viruses. This lets bacteria stay healthy even when they are attacked.
It is possible to delete or alter specific sections of genetic code by using these systems, which have been modified by scientists.
It turns out that Bifidobacterium possesses a large number of native CRISPR-Cas systems, one of which is a type I-G system that has received little research.
In different experiments, the scientists used this internal system and a portable Cas effector called a cytosine base editor to make a Bifidobacterium strain more sensitive to tetracycline, a common antibiotic. Antibiotic resistance is a common trait among bacteria.
Because bacteria may pass on antibiotic resistance to other bacteria in the gut, Pan said, “restoring antibiotic sensitivity is conceptually and practically important.”
Researchers also discovered what they call “single nucleotide polymorphisms” (SNPs) between bacterial strains, which they believe imply substantial variances in phenotypes.
“This was a surprising lesson: One letter difference in strains with genetic codes that are over 99% similar can make huge differences,” Barrangou added.
“What genes turn on and how they behave due to their environment can make a huge difference and will require researchers to customize the CRISPR tool to adapt the editing strategy accordingly.”
Image Credit: Marc Hall, NC State University
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