Without social distancing, how do bacteria survive a viral epidemic?

Like humans struggling to survive the COVID-19 pandemic, bacterial cells need social distancing to defeat the virus. But in some situations, like inside an elevator or inside a candy-colored bacterial structure called a “pink berry,” it’s just not possible to stay isolated.

Looking like sprawling Nerds or Pop Rocks, the communal, multi-lobed pink berries dot the submerged surface of the salt marsh in and around Woods Hole.

New research conducted at the Marine Biological Laboratory (MBL) provides evidence that genetic mechanisms Barry-Making bacteria—and others like them—protect against disease. The study, published in Proceedings of the National Academy of SciencesIt also has implications for understanding the evolution of single-celled organisms like bacteria, including humans, to complex multicellular organisms.

“It tells us about the challenges we faced when we were little balls of cells,” says Lizzie Wilbanks, an MBL Whitman Fellow and microbiologist at the University of California, Santa Barbara. “If you’re building multicellular structures, you have to develop some pretty good immune defenses to survive.”

Mysterious, mutating systems

Wilbanks first encountered pink berries as a graduate student enrolled in MBL’s microbial diversity course. These spherical aggregates are included in the structure of bacteria when genetically similar individuals live near each other and coordinate their activity. Pink berries are inhabited by a type of bacteria called Thiohalocapsa psb1, which feeds on itself using sulfur and light, in addition to a relatively small number of other symbiotic bacteria.

Working together, these cells create oxygen-free pockets, which can poison them, and gain the weight they need to settle safely in their ideal habitat.

Like all organisms, these cooperative microbes are vulnerable to virus infection from their environment. Pink berries and other multicellular bacteria require a lot of protection, because — like us — they consist of genetically similar cells packed tightly together, with no social distancing possible. .

“It’s the perfect cocktail for an epidemic that wipes out everything,” Wilbanks says.

Through his colleague Blair Paul, an assistant scientist at MBL, Wilbanks learned of an unusual genetic mechanism they found abundant in Thiohalocapsa. Known as diversity-inducing retroelements (DGRs), this system consists of segments of DNA that are transcribed into RNA and returned to DNA through an error-prone process, then targeted for mutation. are inserted into the gene.

Thus, DGRs introduce many new genetic variants at specific locations within the genome, the raw material for adaptation. Scientists have found these systems in viruses, bacteria and other microbes called archaea, yet they don’t fully understand how the microbes use them.

Wilbanks and Hugo Doré, then a postdoctoral scientist in his lab and first author of the study, began discussing what functions DGRs might serve for Thiohalocapsa. Through their research, they learned that the target genes of DGRs include components found in the immune systems of multicellular organisms, including humans, plants and even some fungi.

Similarities to parts of the immune system of other organisms led the researchers to suspect that DGRs may encode sensor proteins that Thiohalocapsa uses to defend against pathogens, similar to antibodies in our own immune systems. .

All living things need to detect threats they have never encountered before. Humans and other vertebrates solve this problem by modifying and altering the genes for their sensor proteins (antibodies) to produce a diverse army of sentinels. Although recent research has shown that many components of our innate immune system evolved from bacterial ancestors, scientists have never before seen anything like our hyperdiverse antibodies in bacteria.

A broad immunological connection

The team first looked broadly at DGRs found in bacteria and archaea, focusing on genes responsible for converting RNA to DNA. This method divides DGRs from bacteria and archaea into two groups.

In the group to which Thiohalocapsa belongs, they found that 82% of the DGRs belong to microbes that form multicellular, cooperative structures like the rosy berries. Although they belonged to distantly related microbes, the DGR mutations affect the same types of immune system genes as they do in Theohalokapsa.

Examining hundreds of individual pink berries, they found that DGRs actively modulated 14 of 15 total target genes in Thiohalocapsa. The amount of variation found for these genes varied, however, depending on the location from which the pink berries were collected. Viruses in the same marsh ponds can vary—perhaps the team exaggerated the differences it observed.

“The next frontier is showing what Thiohalocapsa is actually doing with its DGRs in the environment,” Wilbanks says.

In addition to providing a glimpse into the evolution of life, the research has practical implications.

Wastewater treatment plants use multicellular bacteria to remove nutrients that can harm local ecosystems, and federal and industry researchers have explored a number of other applications for engineered clusters of microbes. Looking for These microbial structures face the same challenge—viral outbreaks—as pink berries.

When engineering these microbial systems, it makes sense to mimic the DGR-based immunity of wild commensal bacteria, Wilbanks says.