The mysterious world of Patescibacteria

Scientists have discovered genes essential to the unusual lifestyle of tiny bacteria that live on the surface of larger bacteria.

Batsibacteria are a mysterious group of tiny microbes with elusive survival methods. While scientists can only grow a few of these species, they are part of a diverse family found in many environments.

The few types of Patescibacteria that researchers can grow in the laboratory reside on the surfaces of cells of a larger host microbe. Patescibacteria generally lack the genes needed to synthesize many molecules essential for life, e.g Amino acids Which make up proteins, fatty acids that make up membranes, and the nucleotides contained in them DNA. This has led researchers to speculate that many of them depend on other bacteria to grow.

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

Nitin S. said: “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 never been described before,” said Balija of the institute. of System Biology in Seattle, who contributed many of the computational and systems analyzes for the study.

Epibiotic bacteria researcher Larry A. Gallagher in front of a microscope in the microbiology laboratory at the University of Washington School of Medicine. Credit: S. Brooke Peterson / University of Washington

“The ability to genetically perturb Patescibacteria opens 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 in order to survive.

The team that conducted the study was headed by Joseph Mougus’s laboratory in the Department of Microbiology at the university University of Washington The School of Medicine and the Howard Hughes Medical Institute were interested in B. batischebacteria for several reasons.

They are among many poorly understood bacteria whose DNA sequences appear in large-scale genetic analyzes of genomes found in Classify– Rich microbial communities from environmental sources. This genetic material is referred to as “microbial dark matter” because little is known about the functions it encodes.

Microbial dark matter likely contains information about biochemical pathways with potential biotechnological applications, researchers report. cell paper. They also contain evidence for the molecular activities that support a microbial ecosystem, as well as for the cell biology of the diverse microbial species assembled in this ecosystem.

The group of Patescibacteria analyzed in this latest research belongs to the 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 Mesolithic Age and have been linked to human oral health.

In the human mouth, Saccharomyces bacterium requires the company of actinomycetes, which serve as their host. To better understand the mechanisms that Saccharomyces bacterium uses to communicate with their hosts, the researchers used genetic manipulation to identify all the genes essential for Saccharomyces bacterium growth.

Yaxi Wang, a researcher in abiotic bacteria, at an anaerobic workstation in the microbiology laboratory at the University of Washington School of Medicine in Seattle. Credit: S. Brooke Peterson / University of Washington

“We are very excited to get this first glimpse into the unusual gene functions 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 glycobacteria exploit host bacteria for their growth.”

Potential host interaction factors revealed in the study include cell surface structures that may help glycobacteria attach to host cells and a specialized secretion system that can be used to transport nutrients.

Another application of the authors’ work was the generation of Saccharobacterial cells that express fluorescent proteins. Using these cells, the researchers performed time-lapse fluorescent microscopy imaging of Saccharobacteria growing with their host bacteria.

S. noted. “Time-lapse imaging of host cell cultures of S. glycobacteria has revealed the surprising complexity of the life cycle of this unusual bacterium,” said Brooke Peterson, a senior scientist in the Mogus Laboratory.

Some Saccharomyces bacteria act as mother cells by attaching to the host cell and budding repeatedly to generate small swarm offspring, the researchers report. These little ones move on to search for new host cells. Some of the offspring in turn became mother cells, while others appeared to interact unproductively with the host.

The researchers believe that additional 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 that these organisms contain” and perhaps reveal biological mechanisms that have not yet been envisioned.

Reference: “Genetic manipulation of Patescibacteria provides mechanistic insights into microbial dark matter and abiotic lifestyle” by Yaxi Wang, Larry A. Gallagher, Pia A. Andrade, Andi Liu, Ian R. Humphreys, Serdar Turkarslan, Kevin J. Cutler, Mario. L. Arrieta-Ortiz, Yaqiao Li, Matthew C. Radey, Jeffrey S. McLean, Qian Cong, David Baker, Nitin S. Baliga, S. Brook Peterson and Joseph D. Mougous, September 7, 2023, cell.
doi: 10.1016/j.cell.2023.08.017

This collaborative and interdisciplinary study is enhanced by the newly established Center for Microbiome and Microbiome Interactions (mim_c), which is directed by Mojo. mim_c’s mission is to reduce barriers to microbiome research studies and foster collaboration by connecting with like-minded researchers from various disciplines. Here, mim_c was the catalyst that joined Mouugous’s lab with oral microbiome expert Jeffrey McLean in the Department of Periodontology at the University of Wisconsin School of Dentistry.

Lead authors on this study are Yaxi Wang and Larry A. Gallagher of the University of Wisconsin Department of Microbiology. Senior authors are Baliga, Peterson, and Mogus. Biochemists Qian Kong of the University of Texas Southwestern, David Becker and other researchers from the University of Wisconsin Medical Institute also contributed to the protein design, along with McLean.

Mogus and Baker are investigators at the Howard Hughes Medical Institute. Mogus holds the Lynn M. and Michael D. Garvey Chair at the University of Washington.

The study was supported by grants from National Institutes of HealthThe National Science Foundation, the Department of Defense’s Defense Threat Reduction Agency, the Bill & Melinda Gates Foundation, and the Welch Foundation.