Genetic tools explore microbial dark matter

Batsibacteria are a group of bewilderingly small microbes whose survival is hard to understand. Scientists can only grow a few species, but these bacteria are a diverse group found in many environments.

The few Patescibacteria that researchers can grow in the lab are found on the cell surfaces of another, larger host microbe. Bacteria, in general, lack the genes needed to make many of the molecules essential to life, such as the amino acids that make up proteins, the fatty acids that make up membranes, and the nucleotides in DNA. This has led the researchers to speculate that many of them depend on other bacteria to grow.

In a study published in cellResearchers provide the first glimpse into the molecular mechanisms underlying the unusual lifestyle of Patescibacteria. This achievement was made possible by the discovery of a way to genetically manipulate these bacteria, a progress that opened up a world of potential new research directions.

Nitin S. said: Palega of the institute: “While metagenomics can tell us about the microbes that live on and within our bodies, DNA sequencing alone does not give us insight into their beneficial or harmful activities, especially for organisms that have not been described before.” of System Biology in Seattle, which contributed several computational and systemic analyzes of the study.

“The ability to genetically perturb Patescibacteria opens up the possibility of applying a powerful systems analysis lens to rapidly characterize the unique biology of obligate organisms,” he added, referring to organisms that must subsist on another organism to survive.

The teams behind the study, headed by the lab of Joseph Mogos in the Department of Microbiology at the University of Washington School of Medicine and the Howard Hughes Medical Institute, were interested in the bacterium Bacteria for several reasons.

They are among several poorly understood bacteria whose DNA sequences are turning up in large-scale genetic analyzes of genomes found in species-rich microbial communities from environmental sources. This genetic material is referred to as “microbial dark matter” because so little is known about the functions it encodes.

Microbial dark matter likely contains information about biochemical pathways with potential biotechnological applications, according to the researchers. cell paper. They also contain evidence for the molecular activities that underpin the microbial ecosystem, as well as for the cell biology of the diverse microbial species grouped into that system.

The group of Patescibacteria analyzed in this latest paper belongs to Saccharibacteria. These creatures live in a variety of terrestrial and aquatic environments but are best known for inhabiting the human mouth. They have been part of the human oral microbiome at least since the middle stone age and have been linked to human oral health.

In the human mouth, Saccharomyces cerevisiae require the company of Actinobacteria, which act as their host. To better understand the mechanisms that Saccharomyces use to communicate with their hosts, the researchers used genetic manipulation to identify all of the genes essential for the growth of Saccharomyces.

“We are very excited to get this first glimpse into the functions of the unusual genes that these bacteria harbor,” said Mogos, a professor of microbiology. “By focusing our future studies on these genes, we hope to unravel the mystery of how Saccharomyces cerevisiae exploit host bacteria for their own growth.”

Possible host interaction factors uncovered in the study include cell surface structures that may help saccharomyces bacterium bind to host cells, and a specialized secretion system that could be used to transport nutrients.

Another application of the authors’ work has been the generation of Saccharibacterium cells that express fluorescent proteins. Using these cells, the researchers performed time-lapse fluorescent microscopy of Saccharibacterium coevolving with its host bacteria.

S. pointed out. Brock Peterson, a senior scientist at Mogos Lab: “Time-lapse imaging of Saccharibacterium host cell cultures revealed a surprising complexity in the life cycle of this unusual bacterium.”

The researchers report that some saccharomyces bacteria act as mother cells by attaching to the host cell and budding repeatedly to generate small swarming progeny. These young move on to search for new host cells. Some of the offspring, in turn, became mother cells, while others seemed to interact unproductively with the host.

The researchers believe that further genetic manipulation studies will open the door to a broader understanding of the roles of what they describe as “the rich reserves of microbial dark matter these organisms contain” and may reveal biological mechanisms not yet visualized.

This collaborative, multidisciplinary study is furthered by the newly established Center for Microbial Interactions and the Microbiome (called mim_c for short), which is directed by Mojo. mim_c’s mission is to reduce barriers to research studies of the microbiome and to foster collaboration by connecting with like-minded researchers from across disciplines. Here, mim_c was the catalyst who joined Mougous’ lab with oral microbiome expert Jeffrey McClain in the Department of Periodontology at the University of Wisconsin College of Dentistry.