A scanning electron micrograph shows small purple Patescibacteria cells growing on the surface of much larger cells. New research from the lab of Joseph Mougous at UW Medicine in Seattle reveals their life cycle, their genes and some of the molecular mechanisms that may be behind their unusual lifestyle. These epibiotic bacteria are Southlakia epibionticum. Credit: Yaxi Wang, Wai Pang Chan and Scott Braswell/University of Washington
Scientists are discovering the genes essential to the unusual lifestyle of tiny bacteria that live on the surfaces of larger bacteria.
Patescibacteria are a mysterious group of tiny microbes with elusive methods of survival. Although scientists can only cultivate a handful 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 lab reside on the cell surface of another, larger host microbe. Patescibacteria generally lack the genes necessary to make many molecules necessary for life, such as
amino acids
Amino acids are a set of organic compounds used to build proteins. There are approximately 500 known naturally occurring amino acids, although only 20 appear in the genetic code. Proteins are made up of one or more chains of amino acids called polypeptides. The sequence of the amino acid chain causes the polypeptide to fold into a biologically active form. The amino acid sequences of proteins are encoded in genes. Nine proteinogenic amino acids are called "essential" for humans, because they cannot be produced by the human body from other compounds and therefore must be consumed as food.
“data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]”>amino acids which make up proteins, the fatty acids which form membranes and the nucleotides in
DNA
DNA, or deoxyribonucleic acid, is a molecule composed of two long strands of nucleotides that wrap around each other to form a double helix. It is the hereditary material in humans and almost all other organisms that contains the genetic instructions necessary for development, function, growth and reproduction. Almost all cells in the human body have the same DNA. Most DNA is found in the cell nucleus (where it is called nuclear DNA), but a small amount of DNA can also be found in the mitochondria (where it is called mitochondrial DNA or mtDNA).
“data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]”>DNA. This has led researchers to speculate that many of them rely on other bacteria to grow.
In a study recently published in Cell, researchers present the first insight 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 opened up a world of possible new research directions.
“Although metagenomics can tell us which microbes live on and in our bodies, DNA sequences alone do not give us insight into their beneficial or harmful activities, especially for organisms that have never been characterized before,” said Nitin S. Baliga of the Institute. for System Biology in Seattle, who contributed numerous computational and systems analyzes to the study.
Epibiotic bacteria researcher Larry A. Gallagher stands in front of a microscope in a microbiology lab at the University of Washington School of Medicine. Credit: S. Brook Peterson/University of Washington
“The ability to genetically disrupt Patescibacteria opens the possibility of applying powerful systems analysis optics to rapidly characterize the unique biology of obligate epibionts,” he added, referring to organisms that must live on another organism. to survive.
The teams behind the study, led by the laboratory of Joseph Mougous in the Department of Microbiology of the University
University of Washington
Founded in 1861, the University of Washington (UW, simply Washington, or informally U-Dub) is a public research university located in Seattle, Washington, with additional campuses in Tacoma and Bothell. Ranked as an R1 doctoral research university under the Carnegie Classification of Institutions of Higher Education, the UW is a member of the Association of American Universities.
“data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]”>University of Washington The Faculty of Medicine and the Howard Hughes Medical Institute were interested in Patescibacteria for several reasons.
They are among many poorly understood bacteria whose DNA sequences appear in large-scale genetic analyzes of genomes found in
species
A species is a group of living organisms that share a common set of characteristics and are capable of reproducing and producing fertile offspring. The species concept is important in biology because it is used to classify and organize the diversity of life. There are different ways to define a species, but the most widely accepted is the biological species concept, which defines a species as a group of organisms capable of interbreeding and producing viable offspring in nature. This definition is widely used in evolutionary biology and ecology to identify and classify living organisms.
“data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]”>species-rich microbial communities from environmental sources. This genetic material is called “microbial dark matter” because little is known about the functions it encodes.
Microbial dark matter is likely to contain information about biochemical pathways with potential applications in biotechnology, according to the study. Cell paper. It also contains clues about the molecular activities that support a microbial ecosystem, as well as the cellular biology of the diverse microbial species assembled in that system.
The group of Patescibacteria analyzed in this latest research belongs to the Saccharibacteria. These live in various 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 are linked to human oral health.
In the human mouth, Saccharibacteria need the company of Actinobacteria, which serve as hosts. To better understand the mechanisms used by Saccharibacteria to establish relationships with their hosts, researchers used genetic manipulation to identify all the genes essential for the growth of a Saccharibacterium.
Epibiotic bacteria researcher Yaxi Wang at an anaerobic workstation in a microbiology lab at the University of Washington School of Medicine in Seattle. Credit: S. Brook Peterson/University of Washington
“We are extremely excited to have this first glimpse into the functions of the unusual genes that these bacteria harbor,” said Mougous, a professor of microbiology. “By focusing our future studies on these genes, we hope to unravel the mystery of how Saccharibacteria exploit host bacteria for growth.” »
Possible host interaction factors discovered in the study include cell surface structures that may help saccharibacteria attach to host cells and a specialized secretion system that could be used to transport nutrients.
Another application of the authors’ work was the generation of Saccharibacteria cells that express fluorescent proteins. With these cells, the researchers performed time-lapse microscopic fluorescent imaging of saccharibacteria growing with their host bacteria.
“Time-lapse imaging of Saccharibacteria host cell cultures has revealed surprising complexity in the life cycle of these unusual bacteria,” noted S. Brook Peterson, senior scientist in the Mougous laboratory.
Researchers have reported that some saccharibacteria serve as mother cells by adhering to the host cell and budding repeatedly to generate small swarm offspring. These little ones go in search of new host cells. Some of the progeny in turn became parent cells, while others appeared to interact unproductively with a host.
The researchers believe that additional studies of genetic manipulation will open the door to a broader understanding of the roles of what they described as “the rich stores of microbial dark matter that these organisms contain” and could potentially uncover further biological mechanisms. unimaginable.
Reference: “Genetic manipulation of Patescibacteria provides mechanistic insights into microbial dark matter and epibiotic 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 interdisciplinary and collaborative study was fostered by the newly created Center for Microbial Interactions and the Microbiome (called by its acronym mim_c), led by Mougous. mim_c’s mission is to reduce barriers to microbiome research studies and advance collaborations through connections between like-minded researchers across disciplines. Here, mim_c was the catalyst that joined the Mougous lab with oral microbiome expert Jeffrey McClean of the UW School of Dentistry’s Department of Periodontics.
The lead authors of this study were Yaxi Wang and Larry A. Gallagher of the UW Department of Microbiology. The main authors were Baliga, Peterson and Mougous. Biochemists Qian Cong of the University of Texas Southwest, David Baker and other researchers at the UW Medicine Institute for Protein Design also contributed to the work, alongside McClean.
Mougous and Baker are investigators at the Howard Hughes Medical Institute. Mougous holds the Lynn M. and Michael D. Garvey Endowed Chair at the University of Washington.
The study was funded by grants from
National Institutes of Health
The National Institutes of Health (NIH) is the primary agency of the United States government responsible for biomedical and public health research. Founded in 1887, it is part of the U.S. Department of Health and Human Services. The NIH conducts its own scientific research through its Intramural Research Program (IRP) and provides significant biomedical research funding to non-NIH research facilities through its Extramural Research Program. With 27 different institutes and centers under its umbrella, the NIH covers a broad spectrum of health-related research, including specific diseases, population health, clinical research, and fundamental biological processes. Its mission is to seek fundamental knowledge about the nature and behavior of living systems and the application of this knowledge to improve health, prolong life, and reduce disease and disability.
“data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]”> National Institutes of Healththe National Science Foundation, the Defense Threat Reduction Agency of the Department of Defense, the Bill & Melinda Gates Foundation, and the Welch Foundation.
