Long-term and excessive use of antibiotics has caused the spread of antibiotic resistance. The time- and cost-consuming process of new antibiotic development results in the much slower emergence of new antibacterial drugs than that of bacterial resistance. The emergence of superbugs has been growing to become a dominant challenge in human health. Tigecycline is regarded as the last line of defense to combat multidrug-resistant Klebsiella pneumoniae. However, increasing utilization has led to rising drug resistance and treatment failure. Tigecycline resistance of Klebsiella pneumoniae remains a global problem that urgently needs to be solved.
First, the researchers prepared the tigecycline-loaded TPGS-modified and S-thanatin peptide-functionalized nanorods, Ts-TPGS/Cap/TIG (TTCT), and characterized the properties of TTCT. They found that the prepared Ts-TPGS/Cap nanorods could effectively encapsulate TIG and achieve sustained drug release. The TTCT with particle size of ~25 nm would not disassemble in circulation and displayed excellent stability at room temperature.
Next, the researchers evaluated the antibacterial activity of TTCT and explored the underlying mechanisms of overcoming resistance. They found that Ts-TPGS/Cap exhibited targeting and enhanced accumulation in both Klebsiella pneumonia (KPN) and TRKP through the binding between Ts and LPS. TPGS could exert its inhibitory capacity on the activity of efflux pumps and the expression of acrA, acrB and ramA in TRKP. In this way, the TIG concentration inside bacteria was significantly higher in the TTCT group than other groups. The synergistic antibacterial capacity between Ts and TIG further enhanced the antibacterial activity TTCT, thus overcoming the drug resistance of TRKP.
In mice with pneumonia, Ts-TPGS/Cap specifically accumulated in the lungs. TTCT administration could significantly reduce the white blood cells and neutrophil counts in blood samples, and decrease the total cell and C reactive protein (CRP) levels in bronchoalveolar lavage fluid (BALF). Moreover, TTCT was capable of ameliorating neutrophil infiltration in the lungs and reducing bacterial colonies from BALF, thus apparently increasing the survival rates of mice with pneumonia caused by TRKP.
Overall, a TPGS-based and Ts-modified nanodrug delivery system was designed. The prepared nanorods can enhance tigecycline accumulation in bacteria via the inhibitory effect on efflux pumps exerted by TPGS and the targeting capacity of S-thanatin to bacteria. The synergistic antibacterial capacity between S-thanatin and tigecycline further enhances the antibacterial activity, thus overcoming the tigecycline resistance of TRKP. The findings provide a therapeutic strategy for infections diseases caused by MDR gram-negative bacteria.
News
AI therapy may help with mental health, but innovation should never outpace ethics
Mental health services around the world are stretched thinner than ever. Long wait times, barriers to accessing care and rising rates of depression and anxiety have made it harder for people to get timely help. As a result, governments and health care providers are [...]
Global life expectancy plunges as WHO warns of deepening health crisis Post-COVID
The World Health Organization (WHO) has sounded the alarm on the long-term health repercussions of the COVID-19 pandemic in its newly released World Health Statistics Report 2025. The report reveals a staggering decline in global [...]
Researchers map brain networks involved in word retrieval
How are we able to recall a word we want to say? This basic ability, called word retrieval, is often compromised in patients with brain damage. Interestingly, many patients who can name words they [...]
Melting Ice Is Changing the Color of the Ocean – Scientists Are Alarmed
Melting sea ice changes not only how much light enters the ocean, but also its color, disrupting marine photosynthesis and altering Arctic ecosystems in subtle but profound ways. As global warming causes sea ice in the [...]
Your Washing Machine Might Be Helping Antibiotic-Resistant Bacteria Spread
A new study reveals that biofilms in washing machines may contain potential pathogens and antibiotic resistance genes, posing possible risks for laundering healthcare workers’ uniforms at home. Washing healthcare uniforms at home could be [...]
Scientists Discover Hidden Cause of Alzheimer’s Hiding in Plain Sight
Researchers found the PHGDH gene directly causes Alzheimer’s and discovered a drug-like molecule, NCT-503, that may help treat the disease early by targeting the gene’s hidden function. A recent study has revealed that a gene previously [...]
How Brain Cells Talk: Inside the Complex Language of the Human Mind
Introduction The human brain contains nearly 86 billion neurons, constantly exchanging messages like an immense social media network, but neurons do not work alone – glial cells, neurotransmitters, receptors, and other molecules form a vast [...]
Oxford study reveals how COVID-19 vaccines prevent severe illness
A landmark study by scientists at the University of Oxford, has unveiled crucial insights into the way that COVID-19 vaccines mitigate severe illness in those who have been vaccinated. Despite the global success of [...]
Annual blood test could detect cancer earlier and save lives
A single blood test, designed to pick up chemical signals indicative of the presence of many different types of cancer, could potentially thwart progression to advanced disease while the malignancy is still at an early [...]
How the FDA opens the door to risky chemicals in America’s food supply
Lining the shelves of American supermarkets are food products with chemicals linked to health concerns. To a great extent, the FDA allows food companies to determine for themselves whether their ingredients and additives are [...]
Superbug crisis could get worse, killing nearly 40 million people by 2050
The number of lives lost around the world due to infections that are resistant to the medications intended to treat them could increase nearly 70% by 2050, a new study projects, further showing the [...]
How Can Nanomaterials Be Programmed for Different Applications?
Nanomaterials are no longer just small—they are becoming smart. Across fields like medicine, electronics, energy, and materials science, researchers are now programming nanomaterials to behave in intentional, responsive ways. These advanced materials are designed [...]
Microplastics Are Invading Our Arteries, and It Could Be Increasing Your Risk of Stroke
Higher levels of micronanoplastics were found in carotid artery plaque, especially in people with stroke symptoms, suggesting a potential new risk factor. People with plaque buildup in the arteries of their neck have been [...]
Gene-editing therapy shows early success in fighting advanced gastrointestinal cancers
Researchers at the University of Minnesota have completed a first-in-human clinical trial testing a CRISPR/Cas9 gene-editing technique to help the immune system fight advanced gastrointestinal (GI) cancers. The results, recently published in The Lancet Oncology, show encouraging [...]
Engineered extracellular vesicles facilitate delivery of advanced medicines
Graphic abstract of the development of VEDIC and VFIC systems for high efficiency intracellular protein delivery in vitro and in vivo. Credit: Nature Communications (2025). DOI: 10.1038/s41467-025-59377-y. https://www.nature.com/articles/s41467-025-59377-y Researchers at Karolinska Institutet have developed a technique [...]
Brain-computer interface allows paralyzed users to customize their sense of touch
University of Pittsburgh School of Medicine scientists are one step closer to developing a brain-computer interface, or BCI, that allows people with tetraplegia to restore their lost sense of touch. While exploring a digitally [...]
