Gram-negative bacteria cause a variety of infectious diseases in plants and animals alike. Outbreaks of Salmonella and E. coli infections often make headlines due to their severity, and people have to resort to allopathic as well as natural remedies, increasing the burden on the healthcare system. While antibiotics offer an effective solution against bacterial infections, the increasing incidence of antibiotic-resistant bacteria have prompted researchers to identify other possible treatments against these infections. With technological advances and modern medicine, researchers are looking into the possibility of disrupting the pathogenicity of the bacteria at a molecular level by interfering with molecular processes at the gene as well as protein level.
Gram-negative bacteria, notorious for their infection capability, produce osmo-regulated periplasmic glucans (OPGs)-;long-chain carbohydrates made of multiple glucose units-;in the extracellular and/or periplasmic space. Initially, it was believed that OPGs were by-products produced under low solute concentrations, but recent reports confirm that they are crucial for pathogenicity, symbiosis, cell adhesion, and signaling.
However, the enzymes involved in the synthesis, regulation, and degradation of OPGs are not fully known. Genetic analysis revealed that the removal of opgH and/or opgG genes, partially responsible for OPG synthesis, causes bacteria to lose their infection capability, suggesting strong potential links of these genes with bacterial pathogenicity.
Although the structure of OpgG from E. coli (EcOpgG) has been elucidated, the mechanism of action of OpgG and OpgD from E. coli (EcOpgG and EcOpgD, respectively) remains unclear. Understanding the enzymes involved in OPG synthesis and the mechanisms underlying their function could provide us vital insights into the pathogenicity of Gram-negative bacteria, allowing us to develop more effective ways to deal with bacterial infections.
To bridge this gap in knowledge, Mr. Sei Motouchi from Tokyo University of Science, Dr. Kaito Kobayashi from the National Institute of Advanced Industrial Science and Technology (AIST), Associate, Associate Professor Hiroyuki Nakai from Niigata University and Professor Masahiro Nakajima from the Tokyo University of Science conducted structural and functional analyses of EcOpgD and EcOpgG. The study was published in Communications Biology on September 21, 2023.
Sharing the motivation behind this study, Professor Nakajima tells us, "Glycans are important biological macromolecules that play a variety of roles in living organisms, including pathogenicity and symbiosis. Their structure is very diverse and complex, and thus there are many types of enzymes that may synthesize and degrade them. However, we humans know only a small fraction of them".
The researchers investigated the functions of OPG-related genes in the model organism E. coli. Functional analyses revealed that E. coli OpgD (EcOpgD) was an endo--1,2-glucanase, which specifically broke down -1,2-glucans. It also had similar kinetic properties as those of general glycoside hydrolases (GH), further confirming its identity as a -1,2-glucanase.
Structural analysis using crystallography revealed a high degree of similarity between the structures of EcOpgG and EcOpgD. However, the two enzymes had remarkably different activity. Upon further investigation, the researchers found that a few amino acids forming the reaction pathway, termed 'Loop A', were critical for enzyme activity and regulated the rate of reaction. EcOpgG and EcOpgD differed in their catalytic functions, possibly due to the difference in the amino acids in the Loop A region. The LoopA region diversifies among this group of enzymes, which may lead to functional diversity. Nevertheless, the basis of the catalytic center is shared in this group of enzymes. This common point will help scientists develop therapies that could potentially disrupt OPG synthesis and hinder the infection capability of bacteria.
Further, while the two enzymes belonged to the same family of GHs, their structure did not match with any of the existing GH enzymes. Thus, the authors confirmed that they belonged to a novel GH family, namely GH186. This information opens avenues for research into therapies that can target GH186 proteins to stop the progression of bacterial infections.
Professor Masahiro concludes by explaining the long-term applications of the study, "Although it was known that some Gram-negative plant pathogens synthesize OPGs for pathogenicity, most of the key enzymes for their synthesis had not been identified, preventing the development of agrochemicals targeting OPGs. We have identified a family of enzymes (GH186) involved in the direct synthesis of OPGs and elucidated their detailed functions, which has presented us with new targets (GH186) to inhibit pathogens and provides a solid foundation for 'structure-based pesticide discovery'".
The findings of this study lay down a strong foundation for further investigation of OPGs and related genes and may usher in a new era of disease management.
Source:
Journal reference:
Motouchi, S., et al. (2023). Identification of enzymatic functions of osmo-regulated periplasmic glucan biosynthesis proteins from Escherichia coli reveals a novel glycoside hydrolase family. Communications Biology. doi.org/10.1038/s42003-023-05336-6.
Read the original post:
Scientists uncover key enzymes involved in bacterial pathogenicity - News-Medical.Net
- Close Encounters of Skin and Nerve Cells - The Scientist - April 15th, 2024 [April 15th, 2024]
- OrthoID: Decoding Cellular Conversations with Cutting-Edge Technology - yTech - April 15th, 2024 [April 15th, 2024]
- Impact of aldehydes on DNA damage and aging - EurekAlert - April 15th, 2024 [April 15th, 2024]
- Redefining Cell Biology: Nondestructive Genetic Insights With Raman Spectroscopy - SciTechDaily - March 29th, 2024 [March 29th, 2024]
- Scientists Unravel the Unusual Cell Biology Behind Toxic Algal Blooms - SciTechDaily - March 19th, 2024 [March 19th, 2024]
- Ancient retroviruses played a key role in the evolution of vertebrate brains - EurekAlert - February 21st, 2024 [February 21st, 2024]
- Singapore scientists uncover a crucial link between cholesterol synthesis and cancer progression - EurekAlert - February 4th, 2024 [February 4th, 2024]
- Scientists uncover a way to "hack" neurons' internal clocks to speed up brain cell development - News-Medical.Net - February 4th, 2024 [February 4th, 2024]
- First atomic-scale 'movie' of microtubules under construction, a key process for cell division - EurekAlert - February 4th, 2024 [February 4th, 2024]
- Small RNAs take on the big task of helping skin wounds heal better and faster with minimal scarring - EurekAlert - February 4th, 2024 [February 4th, 2024]
- Shengjie Feng channels the powers of cryogenic electron microscopy - Newswise - January 19th, 2024 [January 19th, 2024]
- Study pinpoints breast cancer cells-of-origi - EurekAlert - January 19th, 2024 [January 19th, 2024]
- New analysis of cancer cells identifies 370 targets for smarter, personalized treatments - News-Medical.Net - January 19th, 2024 [January 19th, 2024]
- EU funding for pioneering research on the treatment of gliomas - EurekAlert - January 19th, 2024 [January 19th, 2024]
- The future of mRNA biology and AI convergence - Drug Target Review - December 22nd, 2023 [December 22nd, 2023]
- The future of artificial breast milk, according to one lab - Quartz - December 22nd, 2023 [December 22nd, 2023]
- Shedding new light on the hidden organization of the cytoplasm - News-Medical.Net - December 22nd, 2023 [December 22nd, 2023]
- Bugs that help bugs: How environmental microbes boost fruit fly reproduction - EurekAlert - December 22nd, 2023 [December 22nd, 2023]
- Cells Move in Groups Differently Than They Do When Alone - NYU Langone Health - December 14th, 2023 [December 14th, 2023]
- Cells move in groups differently than they do when alone - EurekAlert - December 14th, 2023 [December 14th, 2023]
- Seattle Hub for Synthetic Biology plans to transform cells into tiny recording devices - GeekWire - December 14th, 2023 [December 14th, 2023]
- Virginia Tech and Weizmann Institute of Science tackle cell ... - Virginia Tech - October 16th, 2023 [October 16th, 2023]
- Vast diversity of human brain cell types revealed in trove of new ... - Spectrum - Autism Research News - October 16th, 2023 [October 16th, 2023]
- Singamaneni to develop advanced protein imaging method - The ... - Washington University in St. Louis - October 16th, 2023 [October 16th, 2023]
- Researchers find certain cancers can activate 'enhancer' in the ... - University of Toronto - October 16th, 2023 [October 16th, 2023]
- 2023 Hettleman Prizes awarded to five exceptional early-career ... - UNC Research - October 16th, 2023 [October 16th, 2023]
- Faeth Therapeutics Announces National Academy of Medicine ... - BioSpace - October 16th, 2023 [October 16th, 2023]
- From Migrant Farm Worker to Duke Scientist, Everardo Macias ... - Duke University School of Medicine - October 16th, 2023 [October 16th, 2023]
- Finding the golden ticket? Cyclin T1 is required for HIV-1 latency ... - Fred Hutch News Service - October 16th, 2023 [October 16th, 2023]
- Spermidine May Improve Egg Health and Fertility - Lifespan.io News - October 16th, 2023 [October 16th, 2023]
- Molecule discovered that grows bigger and stronger muscles - Earth.com - October 16th, 2023 [October 16th, 2023]
- SGIOY: 3 Biotech Stocks With Potential Future Gains - StockNews.com - October 16th, 2023 [October 16th, 2023]
- Association for Molecular Pathology Publishes Best Practice ... - Technology Networks - October 16th, 2023 [October 16th, 2023]
- A new cell type with links to gastric cancer steps up for its mugshot - Fred Hutch News Service - October 16th, 2023 [October 16th, 2023]
- Programmed cell death may be 1.8 billion year - EurekAlert - October 16th, 2023 [October 16th, 2023]
- New study confirms presence of flesh-eating and illness-causing ... - Science Daily - October 16th, 2023 [October 16th, 2023]
- New Institute for Immunologic Intervention (3i) at the Hackensack ... - Hackensack Meridian Health - October 16th, 2023 [October 16th, 2023]
- Post-doctoral Fellow in Cancer Biology in the Department of ... - Times Higher Education - October 16th, 2023 [October 16th, 2023]
- B cell response after influenza vaccine in young and older adults - EurekAlert - October 16th, 2023 [October 16th, 2023]
- Post-doctoral researcher in yeast cell biology job with UNIVERSITY ... - Times Higher Education - April 8th, 2023 [April 8th, 2023]
- expert reaction to study looking at creating embryo-like structures ... - Science Media Centre - April 8th, 2023 [April 8th, 2023]
- UCF Bone Researcher Receives National Recognition - UCF - April 8th, 2023 [April 8th, 2023]
- PhenomeX to Participate in American Association of Cancer ... - BioSpace - April 8th, 2023 [April 8th, 2023]
- Inland Empire stem-cell therapy gets $2.9 million booster - UC Riverside - April 8th, 2023 [April 8th, 2023]
- New finding in roundworms upends classical thinking about animal cell differentiation - News-Medical.Net - April 8th, 2023 [April 8th, 2023]
- Biology's unsolved chicken-or-egg problem: Where did life come from? - Big Think - April 8th, 2023 [April 8th, 2023]
- Azacitidine in Combination With Trametinib May Be Effective for ... - The ASCO Post - April 8th, 2023 [April 8th, 2023]
- Researchers clear the way for well-rounded view of cellular defects - Phys.org - April 8th, 2023 [April 8th, 2023]
- We were dancing around the lab cellular identity discovery has potential to impact cancer treatments - Newswise - April 8th, 2023 [April 8th, 2023]
- Environmental stressors' effect on gene expression explored in lecture - Environmental Factor Newsletter - April 8th, 2023 [April 8th, 2023]
- RNA therapy restores gene function in monkeys modeling ... - Spectrum - Autism Research News - April 8th, 2023 [April 8th, 2023]
- Traumatic brain injury interferes with immune system cells' recycling ... - Science Daily - April 8th, 2023 [April 8th, 2023]
- Lab-grown fat could give cultured meat real flavor and texture - EurekAlert - April 8th, 2023 [April 8th, 2023]
- Researchers reveal mechanism of polarized cortex assembly in migrating cells - Phys.org - April 8th, 2023 [April 8th, 2023]
- Probing Selfish Centromeres Unveils an Evolutionary Arms Race - The Scientist - April 8th, 2023 [April 8th, 2023]
- Meet the 2023 Outstanding Graduating Students - UMaine News ... - University of Maine - April 8th, 2023 [April 8th, 2023]
- The Worlds Sexiest Fragrance Unveiled, But Its Not For You - Revyuh - April 8th, 2023 [April 8th, 2023]
- City of Hope appoints John D. Carpten, Ph.D., as director of its ... - BioSpace - April 8th, 2023 [April 8th, 2023]
- Modernized Algorithm Predicts Drug Targets for SARS-CoV-2, Other ... - GenomeWeb - April 8th, 2023 [April 8th, 2023]
- BU researcher wins $3.9 million NIH grant to develop novel therapeutic modalities for Alzheimer's - News-Medical.Net - April 8th, 2023 [April 8th, 2023]
- Providing critical insights for animal development - HKU biologists ... - EurekAlert - April 8th, 2023 [April 8th, 2023]
- Students Express Frustrations About the Middle Class Scholarship - The Triton - April 8th, 2023 [April 8th, 2023]
- Mendus redeems the outstanding convertible bonds from Negma ... - GlobeNewswire - April 8th, 2023 [April 8th, 2023]
- Sustainability in research: If you want to green your lab, start with the ... - McGill Reporter - April 8th, 2023 [April 8th, 2023]
- Two-organ chip to answer fatty liver questions - EurekAlert - April 8th, 2023 [April 8th, 2023]
- Blind dating in bacteria evolution - Newswise - April 8th, 2023 [April 8th, 2023]
- White blood cells play unexpected role in clearing out dead liver cells - EurekAlert - April 8th, 2023 [April 8th, 2023]
- Woolly mammoths evolved smaller ears and woolier coats over the 700,000 years that they roamed the Siberian steppes - Newswise - April 8th, 2023 [April 8th, 2023]
- Pathogen mapped: Evolution and potential treatments - Science Daily - March 31st, 2023 [March 31st, 2023]
- ProJenX Announces Formation of Scientific Advisory Board - Yahoo Finance - March 31st, 2023 [March 31st, 2023]
- Science journalist Rebecca Skloot to speak on 'The Immortal Life of ... - Virginia Tech Daily - March 31st, 2023 [March 31st, 2023]
- How cell mechanics influences everything | MIT News ... - MIT News - March 31st, 2023 [March 31st, 2023]
- Artificial Cells The Powerhouse of the Future - SciTechDaily - March 31st, 2023 [March 31st, 2023]
- Basic Science Experts and Information for Media - St. Jude ... - St. Jude Children's Research Hospital - March 31st, 2023 [March 31st, 2023]
- Mendus presents an update on the use of its DCOne platform to source high-quality NK cell therapies at the 8th Annual Innate Killer Summit - Yahoo... - March 31st, 2023 [March 31st, 2023]
- Researchers reveal structural basis of plp2-mediated cytoskeletal protein folding by TRiC/CCT - Phys.org - March 31st, 2023 [March 31st, 2023]
- Labroots Announces Full Agenda for its 5th Annual Bioprocessing ... - PR Web - March 31st, 2023 [March 31st, 2023]
- RoslinCT and Lykan Bioscience announce that the MHRA has granted an MIA License for their cGMP Manufacturing facilities in Edinburgh, UK - Yahoo... - March 31st, 2023 [March 31st, 2023]
- 'ASBMB opened the doors for me' - ASBMB Today - March 31st, 2023 [March 31st, 2023]
- More Fun Than Fun: Science Is Impoverished Without Its Tales - The Wire Science - March 31st, 2023 [March 31st, 2023]