A study from the Centre for Phage Technology, part of Texas A&M’s College of Agriculture and Life Sciences and Texas A&M AgriLife Research, shows how the “hidden” genes in bacteriophages – types of viruses that infect and destroy bacteria – may be key to the development of a new class of antibiotics for human health.
The study has been published in Nature Communications and Current Science Daily, as well as featured in a recent Nature Research Microbiology Community blog post.
Antibiotic-resistant bacteria pose an increasing threat to human health, creating an urgent need for the development of novel antibiotics.
“There has been an increased interest in bacteriophages and their potential as antibacterial agents to fight pathogenic bacteria,” said Centre for Phage Technology director Ryland Young, Ph.D., who supervised the study research. “This is in large part due to the ability of the ‘lysis genes’ of the phage to cause a cellular breakdown in the bacterial host.”
The need for new and more effective antibiotics has increased interest in bacteriophages as possible agents to fight pathogenic bacteria.
Most phages can cause their host cell to rupture, a process called lysis. They also release new “progeny” phage virions that are genetically and structurally identical to the parent virus.
“Small phages, such as the ones this study focuses on, make a single protein which causes host lysis,” Young said. “Basically, the virus produces a ‘protein antibiotic’ that causes lysis in the same way antibiotics like penicillin do – by disrupting the multistage process of cell wall biosynthesis. When the infected cell tries to divide, it blows up because it can’t create the new cell wall between the daughter cells.”
He said these small lysis proteins can be the model for a completely new class of antibiotics.
The study focuses on characterizing the lysis genes of leviviruses, bacteriophages containing small single-stranded RNA genomes with only three to four genes. Tens of thousands of leviviruses have been discovered. Among the known levivirus genes is Sgl, which stands for ‘single gene lysis.’ Sgl encodes a protein that induces the cellular breakdown of bacteria.
“We wanted to discover these ‘hidden’ lysis genes in single-stranded RNA phages, as well as understand how their structure and evolution could benefit development of new, more effective antibiotics,” said Karthik Chamakura, Ph.D., a postdoctoral research associate at the centre and the study’s first author. “We also wanted to investigate how certain molecular targets within bacteria could be identified and exploited for antibiotic development.”
Reference:
https://doi.org/10.1038/s41467-020-19860-0
Study highlights risk of new SARS-CoV-2 mutations emerging during chronic infection
, /in Corona News, E-News /by panglobalSARS-CoV-2 mutations similar to those in the B1.1.7 UK variant could arise in cases of chronic infection, where treatment over an extended period can provide the virus multiple opportunities to evolve, say scientists.
Given that both vaccines and therapeutics are aimed at the spike protein, which we saw mutate in our patient, our study raises the worrying possibility that the virus could mutate to outwit our vaccines
Writing in Nature, a team led by Cambridge researchers report how they were able to observe SARS-CoV-2 mutating in the case of an immune-compromised patient treated with convalescent plasma. In particular, they saw the emergence of a key mutation also seen in the new variant that led to the UK being forced once again into strict lockdown, though there is no suggestion that the variant originated from this patient.
Using a synthetic version of the virus Spike protein created in the lab, the team showed that specific changes to its genetic code – the mutation seen in the B1.1.7 variant – made the virus twice as infectious on cells as the more common strain.
SARS-CoV-2, the virus that causes COVID-19, is a betacoronavirus. Its RNA – its genetic code – is comprised of a series of nucleotides. As the virus replicates itself, this code can be mis-transcribed, leading to errors, known as mutations. Coronaviruses have a relatively modest mutation rate at around 23 nucleotide substitutions per year.
Of particular concern are mutations that might change the structure of the ‘spike protein’, which sits on the surface of the virus, giving it its characteristic crown-like shape. The virus uses this protein to attach to the ACE2 receptor on the surface of the host’s cells, allowing it entry into the cells where it hijacks their machinery to allow it to replicate and spread throughout the body. Most of the current vaccines in use or being trialled target the spike protein and there is concern that mutations may affect the efficacy of these vaccines.
UK researchers within the Cambridge-led COVID-19 Genomics UK (COG-UK) Consortium have identified a particular variant of the virus that includes important changes that appear to make it more infectious: the ΔH69/ΔV70 amino acid deletion in part of the spike protein is one of the key changes in this variant.
Although the ΔH69/ΔV70 deletion has been detected multiple times, until now, scientists had not seen them emerge within an individual. However, in a study published today in Nature, Cambridge researchers document how these mutations appeared in a COVID-19 patient admitted to Addenbrooke’s Hospital, part of Cambridge University Hospitals NHS Foundation Trust.
Reference:
https://doi.org/10.1038/s41586-021-03291-y
Hidden genes could be key in development of new antibiotics
, /in E-News /by panglobalA study from the Centre for Phage Technology, part of Texas A&M’s College of Agriculture and Life Sciences and Texas A&M AgriLife Research, shows how the “hidden” genes in bacteriophages – types of viruses that infect and destroy bacteria – may be key to the development of a new class of antibiotics for human health.
The study has been published in Nature Communications and Current Science Daily, as well as featured in a recent Nature Research Microbiology Community blog post.
Antibiotic-resistant bacteria pose an increasing threat to human health, creating an urgent need for the development of novel antibiotics.
“There has been an increased interest in bacteriophages and their potential as antibacterial agents to fight pathogenic bacteria,” said Centre for Phage Technology director Ryland Young, Ph.D., who supervised the study research. “This is in large part due to the ability of the ‘lysis genes’ of the phage to cause a cellular breakdown in the bacterial host.”
The need for new and more effective antibiotics has increased interest in bacteriophages as possible agents to fight pathogenic bacteria.
Most phages can cause their host cell to rupture, a process called lysis. They also release new “progeny” phage virions that are genetically and structurally identical to the parent virus.
“Small phages, such as the ones this study focuses on, make a single protein which causes host lysis,” Young said. “Basically, the virus produces a ‘protein antibiotic’ that causes lysis in the same way antibiotics like penicillin do – by disrupting the multistage process of cell wall biosynthesis. When the infected cell tries to divide, it blows up because it can’t create the new cell wall between the daughter cells.”
He said these small lysis proteins can be the model for a completely new class of antibiotics.
The study focuses on characterizing the lysis genes of leviviruses, bacteriophages containing small single-stranded RNA genomes with only three to four genes. Tens of thousands of leviviruses have been discovered. Among the known levivirus genes is Sgl, which stands for ‘single gene lysis.’ Sgl encodes a protein that induces the cellular breakdown of bacteria.
“We wanted to discover these ‘hidden’ lysis genes in single-stranded RNA phages, as well as understand how their structure and evolution could benefit development of new, more effective antibiotics,” said Karthik Chamakura, Ph.D., a postdoctoral research associate at the centre and the study’s first author. “We also wanted to investigate how certain molecular targets within bacteria could be identified and exploited for antibiotic development.”
Reference:
https://doi.org/10.1038/s41467-020-19860-0
Critical flaw found in lab models of the human blood-brain barrier
, /in E-News /by panglobalCells used to study the human blood-brain barrier in the lab aren’t what they seem, throwing nearly a decade’s worth of research into question, a new study from scientists at Columbia University Vagelos College of Physicians and Surgeons and Weill Cornell Medicine suggests.
The team also discovered a possible way to correct the error, raising hopes of creating a more accurate model of the human blood-brain barrier for studying certain neurological diseases and developing drugs that can cross it.
The study was published online Feb. 4 in the Proceedings of the National Academy of Sciences (PNAS).
“The blood-brain barrier is difficult to study in humans and there are many differences between the human and animal blood-brain barrier. So it’s very helpful to have a model of the human blood-brain barrier in a dish,” says co-study leader Dritan Agalliu, Ph.D., associate professor of pathology and cell biology (in neurology) at Columbia University Vagelos College of Physicians and Surgeons.
The in vitro human blood-brain barrier model, developed in 2012, is made by coaxing differentiated adult cells, such as skin cells, into stem cells that behave like embryonic stem cells. These induced pluripotent stem cells can then be transformed into mature cells of almost any type – including a type of endothelial cell that lines the blood vessels of the brain and spinal cord and forms a unique barrier that normally restricts the entry of potentially dangerous substances, antibodies, and immune cells from the bloodstream into the brain.
Agalliu previously noticed that these induced human “brain microvascular endothelial cells,” produced using the published approach in 2012, did not behave like normal endothelial cells in the human brain. “This raised my suspicion that the protocol for making the barrier’s endothelial cells may have generated cells of the wrong identity,” says Agalliu.
“At the same time the Weill Cornell Medicine team had similar suspicions, so we teamed up to reproduce the protocol and perform bulk and single-cell RNA sequencing of these cells.”
Their analysis revealed that the supposed human brain endothelial cells were missing several key proteins found in natural endothelial cells and had more in common with a completely different type of cell (epithelial) that is normally not found in the brain.
The team also identified three genes that, when activated within induced pluripotent cells, lead to the creation of cells that behave more like bona fide endothelial cells. More work is still needed, Agalliu says, to create endothelial cells that produce a reliable model of the human blood-brain barrier. His team is working to address this problem.
Reference:
https://doi.org/10.1073/pnas.2016950118
Point-of-Care Fingerstick Testing for Hb and Hct
, /in Advertenties /by 3wmediaBeckman Coulter assists expansion of national network of HIV testing in Uganda
, /in E-News /by Beckman Coulter IncBy Samuel Boova, Director Alliance Development, High Burden HIV Global Markets, Beckman Coulter Life Sciences Despite significant progress in its prevention and treatment, human immunodeficiency virus (HIV) remains a serious public health threat across the globe. The United Nations programme UNAIDS has led the global effort to address the HIV/AIDS crisis and has set out […]
Point of Care testing shown to reduce unnecessary hospital visits
, /in E-News /by 3wmediaThe Oxford Academic Health Science Network (AHSN) has recently published a study exploring the use of point-of-care (PoC) testing within a busy GP group practice in the United Kingdom, using HORIBA Medical’s novel Microsemi CRP PoC haematology analyser.
ESMO guidelines recommend scalp cooling to prevent chemotherapy-induced alopecia
, /in Product News /by 3wmediaThe European Society for Medical Oncology (ESMO), the leading professional organisation for medical oncology, has updated the Clinical Practice Guidelines for Dermatological Toxicities Related to Anticancer Agents to include the recommendation of scalp cooling for the prevention of chemotherapyinduced alopecia (CIA) as a Category IIB recommendation.
Shimadzu releases Advanced i-Series liquid chromatographs
, /in Product News /by 3wmediaShimadzu, one of the world leaders in analytical instrumentation, has release its “Advanced i-Series” liquid chromatographs. The Prominence-i HPLC and Nexera-i UHPLC systems feature pressures of 50 MPa or 70 MPa respectively and can be combined with a variety of detectors. The Advanced i-Series meets user demands for analyzing a large number of samples or […]
Philips introduces industry-first vendor-neutral Radiology Operations Command Center
, /in Product News /by 3wmediaPhilips has unveiled the industry’s first vendorneutral, multimodality, radiology operations command center to add secure, digital, virtual scanner access to existing imaging installs across multiple systems and sites.
RheinCell Therapeutics receives Manufacturing Authorization for iPSCs
, /in Product News /by 3wmediaRheinCell Therapeutics, a developer and manufacturer of human induced pluripotent stem cells (iPSCs) as starting materials for cell therapies, has received Good Manufacturing Practice (GMP) certification and Manufacturing Authorization. This marks a landmark achievement for RheinCell, which is now among a select few iPSCs manufacturers to have received the critical certification.