(Press-News.org) BIRMINGHAM, Ala. – The viruses that infect bacteria are the most abundant biological entities on the planet. For example, a recent simple study of 92 showerheads and 36 toothbrushes from American bathrooms found more than 600 types of bacterial viruses, commonly called bacteriophages or phages. A teaspoon of coastal seawater has about 50 million phages.
While largely unnoticed, phages do not harm humans. On the contrary, these viruses are gaining increasing popularity as biomedicines to eradicate pathogenic bacteria, especially those associated with antibiotic-resistant infections.
In a study published in the journal Nature Communications, Gino Cingolani, Ph.D., of the University of Alabama at Birmingham, and Federica Briani, Ph.D., of the Università degli Studi di Milano, Milan, Italy, have described the full molecular structure of the phage DEV. DEV infects and lyses Pseudomonas aeruginosa bacteria, an opportunistic pathogen in cystic fibrosis and other diseases. DEV is part of an experimental phage cocktail developed to eradicate P. aeruginosa infection in pre-clinical studies.
A peculiar feature of DEV is the presence of a 3,398-amino acid virion-associated RNA polymerase inside the capsid expelled into the bacterium upon infection. Unexpectedly, Cingolani and Briani’s study revealed the virion-associated RNA polymerase is part of a genome ejection motor that pulls the DNA of the phage out of its head after the phage has attached to the surface of a Pseudomonas bacteria using its tail fibers and has penetrated the cell’s outer and inner membranes using its tail tube.
“We posit that the design principles of the DEV ejection apparatus are conserved in all Schitoviridae phages,” Cingolani said. “As of October 2024, over 220 Schitoviridae genomes have been sequenced and are available in the public database. As these genomes are largely unannotated and many open-reading frames have unknown functions, our work paves the way for the facile identification of structural components when a new Schitoviridae phage is discovered.”
The Schitoviridae family of phages “represents some of biology’s most understudied bacterial viruses, increasingly utilized in phage therapy,” Cingolani said. “We are using structural biology to decipher the building blocks and map gene products. This is vital when the amino acid sequence evolves too rapidly for conventional phylogenetic analysis.”
The researchers used cryo-electron microscopy localized reconstruction, biochemical methods and genetic knockouts to describe the complete molecular architecture of DEV, whose DNA genome has 91 open-reading frames that include the giant virion-associated RNA polymerase. “This vRNAP is part of a three-gene operon conserved all Schitoviridae genomes we analyzed,” Cingolani said. “We propose these three proteins are ejected into the host to form a genome ejection motor spanning the cell envelope.”
The structure of DEV and many other phages resembles a minuscule version of Neil Armstrong’s 1969 lunar lander, with a large head, or capsid, that contains the genome and leg-like fibers supporting the phage as it lands on the surface of bacteria, preparing to infect the living bacterial cell.
The researchers determined structures of all the protein capsid factors and tail components in DEV involved in host attachment. Through genetic experiments, they showed that the DEV long tail fibers were essential for infection of P. aeruginosa but were not needed to infect P. aeruginosa mutants whose surface lipopolysaccharide lacked the O-antigen. In general, viruses attach to different cell surface molecules as the first step of infection.
While this study provides several still images of the phage structure, the researchers do not completely understand the movie of DEV infection. They envision three steps in that infection process.
In step one, as a single DEV phage drifts in isolation, its flexible long tail fibers fluctuate to improve the chance of touching a Pseudomonas lipopolysaccharide surface molecule. After the first touch, all five fibers attach to tether the phage perpendicularly close to the bacterial outer surface.
In step two, the short tail fiber, which also acts as a tail plug, touches a secondary receptor on the Pseudomonas and a mechanical signal releases the tail plug.
Up to this point, the three proteins called gp73, gp72 and gp71 have been stored inside the phage head near its tail, with shapes that will dramatically change when they exit the phage head. In step three, when the plug is gone, the three proteins are expelled out of the head and into the bacterial cell envelope. The lead protein, gp73, refolds its shape to form an outer membrane pore with a hollow center. Below that, gp72 refolds into a hollow tube that spans the Pseudomonas periplasm, the space between the bacteria’s outer membrane and its inner membrane. Finally, gp71 crosses the inner membrane and refolds into a large RNA polymerase motor in the bacterial cytoplasm that pulls the phage DNA through the hollow gp73 and gp72 channels and into the Pseudomonas cell.
Cingolani, a professor in the Department of Biochemistry and Molecular Genetics, recently came to UAB to head the new Center for Integrative Structural Biology, approved by the University of Alabama System Board of Trustees this summer. The center will help UAB researchers study the three-dimensional structures of biological macromolecules, such as proteins and nucleic acids, to decipher their function and mechanisms of action.
Integrative structural biology seeks to visualize a complete movie of how macromolecules function, using multiple methods to view molecular structures and how they interact with each other. The primary focus of the UAB Center for Integrative Structural Biology will be studying biological problems related to infection, inflammation, immunity, cancer and neurodegeneration.
Co-authors with Cingolani and Briani in the DEV study, “Integrative structural analysis of Pseudomonas phage DEV reveals a genome ejection motor,” are Ravi K. Lokareddy, UAB Department of Biochemistry and Molecular Genetics; Chun-Feng David Hou, Rutgers, The State University of New Jersey, Piscataway, New Jersey; Francesca Forti and David S. Horner, Università degli Studi di Milano; Stephano M. Iglesias and Fenglin Li, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania; and Mikhail Pavlenok and Michael Niederweis, UAB Department of Microbiology.
Support came from National Institutes of Health grants GM100888, GM140733 and OD030457; and the Fondazione per la ricerca sulla Fibrosi cistica-Associazione Trentina Fibrosi Cistica ODV In ricordo di Pio Nicolini grant FFC#15/2021.
At UAB, Biochemistry and Molecular Genetics, and Microbiology, are departments in the Marnix E. Heersink School of Medicine.
END
Structural biology analysis of a Pseudomonas bacterial virus reveals a genome ejection motor
Bacterial viruses, known as phages, are the most abundant biological entities on the planet and are increasingly used as biomedicines to eradicate antibiotic-resistant pathogenic bacteria.
2024-10-22
ELSE PRESS RELEASES FROM THIS DATE:
Remote tool developed to helped detect autism and developmental delay in children with limited access to specialists
2024-10-22
A Ukrainian researcher has developed a new digital tool for detecting autism and developmental delay in children. Her research has been published in Cambridge University Press journal Cambridge Prisms: Global Mental Health.
The tool incorporates the basic principles of the Kids’ Development Diagnosis and Determining the Risk of Autism (KiDD) methodology, for children aged 1.5 to 6 years old, into mobile app form. It has the potential to help diagnose children more swiftly and efficiently, which could have major positive ...
Texas Accounting Chair Steven Kachelmeier garners coveted award for scholarship
2024-10-22
Texas Accounting Chair Steven Kachelmeier Garners Coveted Award for Scholarship
AUSTIN, Texas — The American Accounting Association (AAA) presented its Lifetime Achievement Award for Behavioral Accounting Research to Steven Kachelmeier, a professor and chair of the Department of Accounting at The University of Texas McCombs School of Business. Kachelmeier, the Thomas O. Hicks Endowed Chair in Business, accepted this prestigious award during the weekend at the association’s 2024 Accounting ...
CABHI launches funding program that ignites innovation to advance healthy aging
2024-10-22
TORONTO, Oct. 22, 2024 – Today, the Centre for Aging + Brain Health Innovation (CABHI), powered by Baycrest launched Ignite, its new funding program to support Canadian innovators designing solutions for older persons. As Canada’s aging population rapidly grows – with nearly 20 per cent of people above the age of 65 – so too will the need for innovations that enhance the lives of older persons, including those impacted by dementia.
Canadian early-stage innovators – including researchers, point-of-care staff, and companies – are developing ...
A fully automated AI-based system for assessing IVF embryo quality
2024-10-22
A new artificial intelligence-based system can accurately assess the chromosomal status of in vitro-fertilized (IVF) embryos using only time-lapse video images of the embryos and maternal age, according to a study from investigators at Weill Cornell Medicine.
The new system, called "BELA,” and described in a paper published Sept. 5 in Nature Communications, is the team’s latest AI-based platform for assessing whether an embryo has a normal (euploid) or abnormal (aneuploid) number of chromosomes—a key determinant of IVF success. Unlike prior AI-based approaches, BELA does not need to consider embryologists' subjective assessments of embryos. ...
Senolytics dasatinib and quercetin for prevention of pelvic organ prolapse in mice
2024-10-22
“This study represents one of the first to evaluate the impact of senolytic agents D+Q on the clinical development of pelvic organ prolapse and expression of proteins associated with cellular senescence in a mouse model.”
BUFFALO, NY- October 22, 2024 – A new research paper was published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science), Volume 16, Issue 19 on September 26, 2024, entitled, “Use of the senolytics dasatinib and quercetin for prevention of pelvic organ prolapse in a mouse animal model.”
Pelvic organ prolapse is a common condition among women ...
UCLA efforts to provide prostate cancer treatment in the community gets $6 million boost
2024-10-22
The UCLA Urology department has been awarded $6 million from the California Department of Health Care Services to continue providing vital care and critical services to underinsured and uninsured Californians diagnosed with prostate cancer.
For the next two years, the additional funding will support the 23-year-old IMPACT program—which stands for Improving Access, Counseling, and Treatment for Californians with Prostate Cancer—and extend the program’s reach and duration, ensuring continued support for California’s most vulnerable populations.
Led ...
Study asks: Can cell phone signals help land a plane?
2024-10-22
ALBUQUERQUE, N.M. — Dangling from a weather balloon 80,000 feet above New Mexico, a pair of antennas sticks out from a Styrofoam cooler. From that height, the blackness of space presses against Earth’s blue skies. But the antennas are not captivated by the breathtaking view. Instead, they listen for signals that could make air travel safer.
Researchers from Sandia National Laboratories and Ohio State University are taking experimental navigation technology to the skies, pioneering a backup system to keep an airplane on course when it cannot rely on global positioning system satellites.
More than 15 miles below the floating cooler, cell phone ...
Artificial intelligence is creating a new way of thinking, an external thought process outside of our minds
2024-10-22
The interaction between humans and artificial intelligence is shaping a new thinking system, a new cognitive scheme, external to the human mind, but capable of enhancing its cognitive abilities. This is called System 0, which operates alongside the two models of human thought: System 1, characterized by intuitive, fast, and automatic thinking, and System 2, a more analytical and reflective type of thinking. However, System 0 introduces an additional level of complexity, radically altering the cognitive landscape in which ...
Reaction conditions tune catalytic selectivity
2024-10-22
UPTON, N.Y. — Chemists at the U.S. Department of Energy’s (DOE) Brookhaven National Laboratory have developed a new theoretical framework for more accurately predicting the behavior of catalysts. These collections of atoms lower the energy needed for countless chemical reactions. The study reveals how conditions such as temperature and pressure can change a catalyst’s structure, efficiency, and even the products it makes. The findings are published in the journal Chem Catalysis.
“Our results highlight the significant impact ...
Verified users on social media networks drive polarization and the formation of echo chambers
2024-10-22
When X (formerly Twitter) changed its verification system in 2022, many foresaw its potential to impact the spread of political opinions on the platform. In a modeling study publishing October 22 in the Cell Press journal iScience, researchers show that having verified users whose posts are prioritized by the platform’s algorithms can result in increased polarization and trigger the formation of echo chambers. Because X’s new verification system allows almost anybody to become verified, this side effect could be taken advantage of by users wishing to manipulate others’ opinions, the researchers say.
“Our findings confirm ...
LAST 30 PRESS RELEASES:
QUT scientists create material to turn waste heat into clean power
Major new report sets out how to tackle the ‘profound and lasting impact’ of COVID-19 on cardiovascular health
Cosmic crime scene: White dwarf found devouring Pluto-like icy world
Major report tackles Covid’s cardiovascular crisis head-on
A third of licensed GPs in England not working in NHS general practice
ChatGPT “thought on the fly” when put through Ancient Greek maths puzzle
Engineers uncover why tiny particles form clusters in turbulent air
GLP-1RA drugs dramatically reduce death and cardiovascular risk in psoriasis patients
Psoriasis linked to increased risk of vision-threatening eye disease, study finds
Reprogramming obesity: New drug from Italian biotech aims to treat the underlying causes of obesity
Type 2 diabetes may accelerate development of multiple chronic diseases, particularly in the early stages, UK Biobank study suggests
Resistance training may improve nerve health, slow aging process, study shows
Common and inexpensive medicine halves the risk of recurrence in patients with colorectal cancer
SwRI-built instruments to monitor, provide advanced warning of space weather events
Breakthrough advances sodium-based battery design
New targeted radiation therapy shows near-complete response in rare sarcoma patients
Does physical frailty contribute to dementia?
Soccer headers and brain health: Study finds changes within folds of the brain
Decoding plants’ language of light
UNC Greensboro study finds ticks carrying Lyme disease moving into western NC
New implant restores blood pressure balance after spinal cord injury
New York City's medical specialist advantage may be an illusion, new NYU Tandon research shows
Could a local anesthetic that doesn’t impair motor function be within reach?
1 in 8 Italian cetacean strandings show evidence of fishery interactions, with bottlenose and striped dolphins most commonly affected, according to analysis across four decades of data and more than 5
In the wild, chimpanzees likely ingest the equivalent of several alcoholic drinks every day
Warming of 2°C intensifies Arctic carbon sink but weakens Alpine sink, study finds
Bronze and Iron Age cultures in the Middle East were committed to wine production
Indian adolescents are mostly starting their periods at an earlier age than 25 years ago
Temporary medical centers in Gaza known as "Medical Points" (MPs) treat an average of 117 people daily with only about 7 staff per MP
Rates of alcohol-induced deaths among the general population nearly doubled from 1999 to 2024
[Press-News.org] Structural biology analysis of a Pseudomonas bacterial virus reveals a genome ejection motorBacterial viruses, known as phages, are the most abundant biological entities on the planet and are increasingly used as biomedicines to eradicate antibiotic-resistant pathogenic bacteria.