Houston: Chemists have demonstrated that light-activated molecular machines can drill holes through gram-negative and gram-positive bacteria membranes, killing them in as little as two minutes. Their study suggests a new way to combat antibiotic-resistant bacteria, which lack natural defences against mechanical intruders. The study has been published in the journal, "Science Advances, 2022" The latest iteration of nanoscale drills developed at Rice University is activated by visible light rather than ultraviolet (UV), as in earlier versions. These have also proven effective at killing bacteria through tests on real infections.Six variants of molecular machines were successfully tested by Rice chemist James Tour and his team. All of them punched holes in the membranes of gram-negative and gram-positive bacteria in as little as two minutes. Resistance was futile for bacteria that have no natural defences against mechanical invaders. That means they are unlikely to develop resistance, potentially offering a strategy to defeat bacteria that have become immune to standard antibacterial treatments over time. "I tell students that when they are my age, antibiotic-resistant bacteria are going to make COVID look like a walk in the park," Tour said. "Antibiotics won't be able to keep 10 million people a year from dying of bacterial infections. But this really stops them." Because extended exposure to UV can be damaging to humans, the Rice lab has been refining its molecules for years. The new version gets its energy from still-blueish light at 405 nanometers, spinning the molecules' rotors at 2 to 3 million times per second. It's been suggested by other researchers that light at that wavelength has mild antibacterial properties of its own, but the addition of molecular machines supercharges it, said Tour, who suggested bacterial infections like those suffered by burn victims and people with gangrene will be early targets.The machines are based on Nobel Prize-winning work by Bernard Feringa, who developed the first molecule with a rotor in 1999 and got the rotor to spin reliably in one direction. Tour and his team introduced their advanced drills in a 2017 Nature paper. The Rice lab's first tests of the new molecules on burn wound infection models confirmed their ability to quickly kill bacteria, including methicillin-resistant Staphylococcus aureus, a common cause of skin and soft tissue infections that was responsible for more than 100,000 deaths in 2019. The team achieved visible light activation by adding a nitrogen group. "The molecules were further modified with different amines in either the stator (stationary) or the rotor portion of the molecule to promote the association between the protonated amines of the machines and the negatively charged bacterial membrane," said Liu, now a scientist at Arcus Biosciences in California.The researchers also found the machines effectively break up biofilms and persister cells, which become dormant to avoid antibacterial drugs. "Even if an antibiotic kills most of a colony, there are often a few persister cells that for some reason don't die," Tour said. "But that doesn't matter to the drills." As with earlier versions, the new machines also promise to revive antibacterial drugs considered ineffective. "Drilling through the microorganisms' membranes allows otherwise ineffective drugs to enter cells and overcome the bug's intrinsic or acquired resistance to antibiotics," said Santos, who's on the third year of the postdoctoral global fellowship that brought her to Rice for two years and is continuing at the Health Research Institute of the Balearic Islands in Palma, Spain.The lab is working toward better targeting bacteria to minimize damage to mammalian cells by linking bacteria-specific peptide tags to the drills to direct them toward pathogens of interest. "But even without that, the peptide can be applied to a site of bacterial concentration, like in a burn wound area," Santos said.—ANI

Chemists have demonstrated that light-activated molecular machines can drill holes through gram-negative and gram-positive bacteria membranes, killing them in as little as two minutes. 

To treat infections, visible light activates molecular machineries: Study

Boston: Over the past ten years, the human microbiome has attracted a lot of attention due to research suggesting that disturbed bacterial communities are to blame for a variety of illnesses, including irritable bowel syndrome, dermatitis, and autoimmune diseases. The majority of research has concentrated on the microbiome found in the human stomach. Still, there is a growing consensus that another frequently understudied bacterial population, that of the vagina, merits equal study.
Bacterial vaginosis (BV), which affects about 30 per cent of reproductive-aged women worldwide and is expected to cost USD 4.8 billion to cure each year, is brought on by disturbances of the vaginal microbiome. Pre-term birth, the second-leading cause of newborn death, and several sexually transmitted infections, including HIV, are both made more likely by BV in pregnant women.
Antibiotics are now used to treat BV, but the condition frequently returns and can result in more serious problems such as pelvic inflammatory disease and even infertility. Living biotherapeutics are being investigated for the treatment of BV, just as probiotics are now being prescribed to treat gut problems. The human vaginal microbiome differs significantly from those of popular animal models, making it challenging to undertake preclinical experiments. According to studies, lactobacilli bacteria make up more than 70 per cent of the vaginal microbiome in healthy humans, but less than 1 per cent in the vaginal microbiomes of other mammals. Researchers at the Wyss Institute at Harvard University have created a solution to that problem in the form of a new Organ Chip that replicates the human vaginal tissue microenvironment including its microbiome in vitro. Composed of the human vaginal epithelium and underlying connective tissue cells, the Vagina Chip replicates many of the physiological features of the vagina and can be inoculated with different strains of bacteria to study their effects on the organ's health. The chip is described in a new paper published in Microbiome.
Modelling the vaginal microbiome: The Bill and Melinda Gates Foundation provided financing for the creation of the Vagina Chip, which had the goal of developing a biotherapeutic therapy for BV and advancing it into human clinical trials in order to lower the incidence of infant mortality, genital infections, and pregnancy problems. especially in countries with few resources.
"A major stumbling block for that effort was that there were no good preclinical models that could be used to study which therapies can actually treat BV in human tissues. Our team's project was to create a human Vagina Chip to aid in the development and testing of new therapies for BV," said co-author Aakanksha Gulati, PhD, a Postdoctoral Researcher at the Wyss Institute.
The scientists seeded the top channel of a polymer chip with human vaginal epithelial cells using the microfluidic Organ Chip technology, which was created at the Wyss Institute and then licenced to Emulate. The other side of the permeable membrane between the top and bottom channels was then supplemented with human uterine fibroblast cells. The 3D design resembled the human vaginal wall in structure.
The Vagina Chip has grown several unique layers of differentiated cells after five days that mirrored those in human vaginal tissue. The Vagina Chip's gene expression patterns varied in response to the introduction of the female sex hormone estradiol (a kind of oestrogen), showing that it was hormone sensitive--another essential quality for in vitro reproduction of human reproductive organs.
The scientists then moved to study the vaginal microbiome armed with a living replica of the human vagina. They collaborated with Dr Jacques Ravel, PhD, and his group at the University of Maryland School of Medicine, who had developed three different consortia, each of which contained multiple strains of Lactobacillus crispatus, in light of recent research showing that healthy human vaginal microbiomes typically contain multiple strains of Lactobacillus bacteria.
After three days, all three of these consortia successfully colonised the Vagina Chip after being introduced. Lactic acid, which contributes to maintaining the vagina's low pH and prevents the growth of other microbes, was also started by the consortia.
Beyond helping to maintain an acidic environment, the presence of the L. crispatus bacteria also affected the Vagina Chip's innate immune responses. Chips with bacterial consortia produced lower levels of several inflammation-causing cytokine molecules than chips without the bacteria, which is consistent with the current theory that these "good" microbes help keep inflammation in check in healthy human vaginas.
Bad bacterial tenants, on a chip: Having created a healthy Vagina Chip with optimal bacterial residents, the team then conducted a new experiment in which they inoculated chips with different species of bacteria that are associated with BV: Gardnerella vaginalis, Prevotella bivia, and Atopobium vaginae. A consortium of those three "bad" microbes caused the chips' pH to increase, damaging the vaginal epithelial cells and significantly increasing the production of multiple proinflammatory cytokines - all responses that were similar to what has been observed in human patients with BV. —ANI
"It was very striking that the different microbial species produced such opposite effects on the human vaginal cells, and we were able to observe and measure those effects quite easily using our Vagina Chip," said co-author Abidemi Junaid, PhD, a Research Scientist at the Wyss Institute.
"The success of these studies demonstrate that this model can be used to test different combinations of microbes to help identify the best probiotic treatments for BV and other conditions."
The team is now using the Vagina Chip to test new and existing treatments for BV to identify effective therapies that can be advanced into clinical trials. They are also working on integrating immune cells into the chip to study how the vaginal microbiome might drive systemic immune system responses.
"There is growing recognition that taking care of women's health is critical for the health of all humans, but the creation of tools to study human female physiology is lagging," said senior author Don Ingber, M.D., PhD, who is the Wyss Institute's Founding Director. "We're hopeful that this new preclinical model will drive the development of new treatments for BV as well as new insight into female reproductive health." Ingber is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School and Boston Children's Hospital and the Hansjorg Wyss Professor of Bioinspired Engineering at the Harvard John A. Paulson School of Engineering and Applied Sciences. (ANI)

Over the past ten years, the human microbiome has attracted a lot of attention due to research suggesting that disturbed bacterial communities are to blame for a variety of illnesses, including irritable bowel syndrome, dermatitis, and autoimmune diseases. 

Women's Health: Breakthrough In Bacterial Vaginosis Treatment

Roorkee: Researchers at the Indian Institute of Technology (IIT) Roorkee have identified a new antibacterial small molecule that could help in the fight against drug-resistant infections.
The molecule IITR00693 was discovered after a rigorous screening process. It has shown potent antibacterial activity against a wide range of gram-positive and gram-negative bacteria, including some of the most problematic drug-resistant strains.
The rise of antibiotic resistance among skin-infecting pathogens poses an urgent threat to public health and has fueled the search for new therapies. Enhancing the potency of currently used antibiotics is an alternative for the treatment of infections caused by drug-resistant pathogens, the researchers said.
They found that IITR00693 enhances the activity of antibiotics that are used in the treatment of bacterial infections, particularly against two notorious multidrug-resistant skin-infecting pathogens, namely Staphylococcus aureus and Pseudomonas aeruginosa.
IITR00693 acts like a dual sword; it not only strikes down the most stubborn bacteria but also prevents the emergence of resistance, ensuring that it remains effective for generations to come, the researchers explained.
"We aimed to identify a small molecule that can potentiate currently used antibiotics. IITR00693, a novel antibacterial small molecule, potentiates the antibacterial activity of polymyxin B against Staphylococcus aureus and Pseudomonas aeruginosa," said Prof Ranjana Pathania, Department of Biosciences and Bioengineering, IIT Roorkee, in a statement.
The team investigated in detail the mode of action of this interaction and the molecule's capability to combat soft-tissue infections caused by S. aureus and P.aeruginosa. "The results indicate that IITR00693 has the highest safety index and efficacy. The synergy between IITR00693 and polymyxin B against Gram-positive S. aureus was intriguing, as polymyxin B is specifically active against Gram-negative bacteria," said Mahak Saini, Department of Biosciences and Bioengineering, IIT Roorkee. The findings are published in the American Chemical Society Journal-ACS Infectious Diseases. The team of researchers now aim to "further develop the molecule into a viable therapeutic agent that can be tested in clinical trials", said Prof K K Pant, Director, IIT Roorkee, in the statement. "This is an important step in the development of new antibiotics, as it will allow for the evaluation of the molecule's safety, efficacy, and potential side effects in soft and skin tissue infections," Pant added.
—IANS

Researchers at the Indian Institute of Technology (IIT) Roorkee have identified a new antibacterial small molecule that could help in the fight against drug-resistant infections.

IIT Roorkee Identifies New Antibacterial Molecule To Fight Superbugs

Jodhpur: Researchers at the Indian Institute of Technology (IIT) Jodhpur have used snake venom to develop a novel antimicrobial peptide molecule that can kill bacteria like E. coli, P. aeruginosa, K. pneumoniae, and MRSA (methicillin-resistant Staphylococcus aureus) — all known to create deadly infections.
Bacterial antibiotic resistance is a prevailing global menace that scientists must tackle worldwide.
Most naturally occurring antimicrobial peptides have varying hydrophobicities and charge compositions, limiting their use as human therapeutic molecules despite their potent bacteria-killing ability.
The antimicrobial peptide SP1V3_1 can therapeutically be implemented as a component of an ointment for wound disinfection and healing. It can be biocompatible based on in-vitro cytotoxicity studies.
The researchers’ main aim was to reduce toxicity of the snake venom without losing its antimicrobial property. For that, the scientists truncated the snake venom peptide and eliminated the toxic part of snake venom and further stitched helical short peptide at N-terminus (the end with a free amino group) for the smooth entry of the newly designed therapeutic inside the bacterial cell.
The invented peptide also holds the potential to be developed into a marketable pharmaceutical product, said researchers in the paper published in the Journal of Medicinal Chemistry.
“In the era of developmental stagnation of antibiotics due to the ever-increasing problem of antimicrobial resistance, antimicrobial peptides are exciting leads in the development of novel biocidal agents. The invented antimicrobial peptide SP1V3_1 holds the potential to be developed into a marketable pharmaceutical product, as and when it passes the requisite trials,” said Dr. Surajit Ghosh, Professor, Department of Bioscience &amp; Bioengineering and Smart Healthcare Department, IIT Jodhpur, in a statement.
“The peptide can therapeutically be implemented as a component of an ointment (alone or in combination with other drugs/peptides) for wound disinfection and healing, as an injectable/oral drug for systemic administration, or as an aerosolised formulation to treat a wide range of respiratory bacterial pathogens,” he added.
—IANS

Researchers at the Indian Institute of Technology (IIT) Jodhpur have used snake venom to develop a novel antimicrobial peptide molecule

IIT Jodhpur researchers turn to snake venom to fight antibiotic resistance

London: Scientists have developed a promising antibiotic candidate against a hospital superbug, using a methodology that may be important in the fight against antimicrobial resistance. The team from the Norwegian University of Science and Technology (NTNU) developed a combination of two new substances that effectively kills methicillin-resistant Staphylococcus aureus (MRSA). These substances may become a completely new antibiotic that kills MRSA much more effectively than when used separately and is als effective against a wide group of bacteria, according to the findings published in the Frontiers in Microbiology journal. "Antimicrobial resistance is a major problem, and being able to help solve it is really great," said lead author Amanda Holstad Singleton, a doctoral candidate at NTNU. "It's one thing to develop new antibiotic candidates which, when combined, prove to be well tolerated by human cells, but developing a technology to study how the antibiotic works inside the bacterial cells is equally important," Singleton said. To analyse how the two substances worked, the team developed a method that analyses how the bacterium's signalling proteins react to the treatment. The method provides researchers with a completely new tool in the search for new antibiotic candidates. "Up to 10,000 proteins can be found inside a bacterial cell. Instead of looking at all of them, we 'fish' out the 2000 or so proteins that are signalling proteins. These proteins control much of what happens in the cells," Singleton said. The method allows researchers to see whether each of these proteins is activated or deactivated after adding the substance they want to test. Approximately four years ago, researchers at NTNU published the bactericidal properties of a particular type of peptide. These peptides, in combination with a new compound developed may now become a completely new type of antibiotic. "Peptides are chains of amino acids, which are the building blocks of proteins. What is special about these particular peptides is that they bind to a protein in the bacteria that is absolutely essential for bacteria to be able to copy their DNA," said Professor Marit Otterlei, from the varsity. The peptide prevents DNA copying, and thus, the bacterium dies. "No other antibiotics attack this protein. That means it is a new target, and there are therefore no bacteria that are resistant to these peptides. Since this target protein is found in all bacteria, these peptides also work on multidrug-resistant bacteria," Otterlei said. —IANS

Scientists have developed a promising antibiotic candidate against a hospital superbug

Scientists Develop New Antibiotics To Fight Hospital Superbug

New Delhi (The Hawk): An eco-friendly wound dressing material made using banana fibers presents a sustainable solution for wound care. India, the world's largest banana-farming country, has an abundance of banana pseudo stems, discarded after harvest. In a pioneering effort, scientists at the Institute of Advanced Study in Science and Technology (IASST), an autonomous institute under the Department of Science and Technology, have transformed banana pseudo stems, often considered agricultural waste, into an eco-friendly wound dressing material. Led by Prof. Devasish Chowdhury and Prof. (Retd) Rajlakshmi Devi, the research team, including Mridusmita Barman, a research scholar in the IASST-Deakin University Joint PhD programme, have ingeniously combined the banana fibres with biopolymers like chitosan and guar gum to create a multifunctional patch with excellent mechanical strength and antioxidant properties. Taking it a step further, the researchers loaded the patch with an extract from the Vitex negundo L. plant, demonstrating the capabilities of plant extract-loaded banana fibre-biopolymer composite patch in vitro drug release and as antibacterial agents. All the materials used in creating this innovative dressing material are natural and locally available, making the manufacturing process simple, cost-effective, and non-toxic. The wound dressing material presents a sustainable solution for wound care and suggests additional uses for the abundant banana plant, which may benefit farmers and minimize environmental impact. “This investigation opens the door to a new era in wound healing, offering a low-cost, reliable, and environmentally friendly alternative that holds significant potential in biomedical research,” says Prof. Chowdhury. The banana fiber-biopolymer composite dressing could revolutionize wound care with its broad applications and positive impact on health and the environment. Elsevier recently published this work in the International Journal of Biological Macromolecules. The groundbreaking research has recently been published in the International Journal of Biological Macromolecules by Elsevier, further highlighting its significance in the scientific community.

 An eco-friendly wound dressing material made using banana fibers presents a sustainable solution for wound care

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To treat infections, visible light activates molecular machineries: Study

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The Hawk

Tag : Bacterial

To treat infections, visible light activates molecular machineries: Study

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