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HKU scientists pioneer dual trojan horse approach to combat superbugs

In the relentless battle against antibiotic-resistant superbugs, science continues to unveil ingenious strategies to address their vulnerability. Like…



In the relentless battle against antibiotic-resistant superbugs, science continues to unveil ingenious strategies to address their vulnerability. Like other bacteria, superbugs have a unique weakness – their dependence on iron for growth and survival. Iron serves as an essential nutrient that bacteria utilise for various cellular processes, including DNA replication, energy production, and other vital functions. In essence, iron is like a ‘food’ for bacteria.

Credit: Nature Communications

In the relentless battle against antibiotic-resistant superbugs, science continues to unveil ingenious strategies to address their vulnerability. Like other bacteria, superbugs have a unique weakness – their dependence on iron for growth and survival. Iron serves as an essential nutrient that bacteria utilise for various cellular processes, including DNA replication, energy production, and other vital functions. In essence, iron is like a ‘food’ for bacteria.

Building upon this understanding, a research team led by Professor Hongzhe SUN from the Department of Chemistry, The University of Hong Kong (HKU), introduced a ‘Dual Trojan Horse’ strategy, where a metal-based-drug and sideromycins, a class of antibiotic structurally resembling iron, work together in combating antibiotic-resistant bacteria. This approach allows these antibiotics to be delivered into bacterial cells through a pathway that mimics iron uptake. When bacteria encounter sideromycins, they are deceived into believing they are acquiring iron, prompting them to usher these compounds into their cells. This strategy not only enhances the effectiveness of sideromycins but also prolongs their lifespan, marking a significant advancement in our battle against antibiotic resistance. These promising results were successfully replicated in a live mice model, introducing an innovative strategy to combat antimicrobial resistance, offering hope in the fight against superbugs in clinic. These findings have recently been published a in Nature Communications entitled ‘Metallo-sideromycin as a dual functional complex for combating antimicrobial resistance (AMR)’.

‘We are short of new antibiotics, and infection caused by resistant bacteria (i.e. superbugs) may lead to another pandemic. We have uncovered a dual Trojan Horse strategy to restore antibiotics activity, such as cefiderocol, and hope to provide a novel arsenal for combating antimicrobial resistance,’ commented Professor Sun.

Research Background
Antimicrobial resistance (AMR) in bacterial infections has emerged as a significant global health concern. The overuse and misuse of existing antibiotics have accelerated the acquired drug resistance in bacteria, resulting in resistance to almost all antibiotics used in clinical settings across various bacteria strains.

Gram-negative bacterial infections, such as those caused by Pseudomonas aeruginosa, pose significant challenges in treatment due to their complicated structure. For example, the high resistance of P. aeruginosa against conventional antibiotics can be attributed in part to the limited permeability of the outer membrane (OM) and the expression of ‘efflux pump’, specialised proteins within bacteria that actively remove antibiotics, thus reducing their effectiveness. These factors collectively impede the accumulation of antibiotics at the bacterial target site.

Gram-negative bacteria, including Pseudomonas aeruginosa, can cause a range of infections in humans. These infections often affect the respiratory system, leading to pneumonia or lung infections, as well as urinary tract infections. They can also lead to skin and soft tissue infections, bloodstream infections (sepsis), and infections in wounds or surgical sites. In severe cases, these infections can be particularly challenging to treat due to the bacteria’s resistance to antibiotics, making them a significant health concern. For these reasons, there is now an urgent need for both new antibiotic discovery and other modifications or strategies to enhance or prolong the antibacterial activity of existing clinical antibiotics.

Sideromycin is a novel type of antibiotic where the parent antibiotics or prodrug incorporates a siderophore molecule that utlises iron transport system for delivery. This incorporation enables the active transport of the antibiotic into bacterial cell through nutrient pathways. Cefiderocol (FetrojaÒ) is a recently FDA-approved sideromycin antibiotic in 2019. The antibacterial activity of cefiderocol is improved under the iron-deficient condition because of the enhanced uptake of cefiderocol, with a component of catechol, which coordinate with iron and facilitate the transportation of cefiderocol-iron complex in P. aeruginosa.

Although the frequency of resistance of P. aeruginosa to cefiderocol is much lower than its parent antibiotic ceftazidime, the resistance to cefiderocol was developed inevitably in several Gram-negative bacteria strains recently, for example, in Carbapenem-Resistant Escherichia coli strains and Acinetobacter baumannii in the burned infections. Resistance to cefiderocol was related to the production of β-lactamases, siderophore receptor mutations, expression of efflux pump and the combination of these mechanisms.

Metal compounds have been used as promising antimicrobial agents for years and show low resistance frequency since they are multi-targeted modes of action. Bismuth (Bi3+) compounds have exhibited potent antibacterial properties against bacterial that have become resistant to a variety of antibiotics. These bismuth compounds act as versatile inhibitors of a group of enzymes called metallo-β-lactamase inhibitors, which are involved in antibiotic resistance. Gallium(Ga3+) also offers antibacterial activities by disrupting Iron (Fe3+)uptake system and iron homeostasis.

Interestingly, catecholate siderophores exhibit exceptionally high affinity not only to iron (Fe3+), but also to metals like bismuth (Bi3+) and gallium (Ga3+). These metals behave similarly to iron when they link up with catecholate molecules. These special catechol-metal combinations have been observed to do two things: they can compete with iron to get inside bacterial cells, and they can imitate iron in biological systems, disrupting important iron functions. Thus, the team propose a dual ‘Trojan Horse’ strategy to ‘sneak in’ the antibiotic sideromycins and metal ions simultaneously through siderophore receptor, the same pathways that bacteria use to grab nutrients, leading to synergistic effect against bacterial infections.

Key findings
In this study, the team demonstrated a bismuth drug (CBS) could enhance the potency of cefiderocol against P. aeruginosa in both laboratory experiment (in vitro) and live animal test (in vivo). This enhancement included improved efficacy against biofilm formation by cefiderocol, suppression of the development of high-level bacterial resistance to cefiderocol, and restoration of the efficacy of cefiderocol against resistant P. aeruginosa strains, including those isolated from clinical cases involving real patients.

Such phenomena are likely due to the competition of Bi3+ with Fe3+ to cefiderocol, which leads to decreased uptake of Fe3+ and increased uptake of antimicrobial Bi3+/Ga3+. This competition disrupts the integrity of bacterial membrane, making antibiotic more permeable.

The in vitro interaction of Bi3+ with cefiderocol was confirmed by both UV-vis spectroscopy and MS spectrometry, analytical techniques which confirmed the interaction between Bi3+ and cefiderocol, resulting in the formation of a 1:1 complex of Bi3+-cefiderocol. The metallo-sideromycin might not only improve the efficiency of sideromycin, but also prolong the effective life span of this type of antibiotics. Their animal studies have further validated the efficacy of the approach. It is worth of further investigation of other sideromycins and metals, to thoroughly explore the potentials of metallo-sideromycins in treating infections caused by drug-resistant bacterial pathogens. The research team has filed a patient for the discovery.

About the research team
This study was done jointly by the Department of Chemistry, Department of Microbiology and Carol Yu Centre for Infection, The University of Hong Kong. Ms Chenyuan WANG and Dr Yushan XIA are the co-first authors of this paper. Other members of participating in the research include Dr Hongyan LI, Dr Patrick H TOY, Dr Runming WANG, postgraduate student Ms Jingru LI, and Mr Chun-Lung CHAN of Department of Chemistry, Professor Richard Yi-Tsun KAO of Department of Microbiology, Professor Pak-Leung HO of Carol Yu Centre for Infection. This research was supported by the Research Grants Council of Hong Kong SAR (R7070-18, 17308921, 2122-7S04), the Health and Medical Research Fund of the Health Bureau of Hong Kong SAR (CID HKU1-13) and The University of Hong Kong (URC (202107185074) and Norman & Cecilia Yip Foundation).

About Professor Hongzhe Sun
Professor Hongzhe Sun is the Norman & Cecilia Yip Professor in Bioinorganic Chemistry and Chair Professor of Chemistry at The University of Hong Kong. His research focuses on metalloproteomics and metallomics, the discovery of antimicrobial and antiviral agents, and inorganic chemical biology. Dr Hongyan Li is a Research Assistant Professor in the Department of Chemistry at The University of Hong Kong.

To view the research paper ‘Metallo-sideromycin as a dual functional complex for combating antimicrobial resistance’, please visit:

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For media enquiries, please contact Ms Casey To, External Relations Officer (tel: 39174948; email: / Ms Cindy Chan, Assistant Director of Communications of HKU Faculty of Science (tel: 3917 5286; email:

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Guerilla gardening: how you can make your local area greener without getting into trouble

Many people are gardening on land that is not theirs – here are some things to consider to avoid getting into trouble.



What are your rights if you want to become a guerrilla gardener? Goami/Shutterstock

When Richard Reynolds first started gardening around London’s streets, he was so worried he might be arrested that he worked under the cover of darkness. Reynolds was one of the UK’s first modern guerrilla gardeners, a movement that encourages people to nurture and revive land they do not have the legal rights to cultivate.

Gardening, in general, offers physical and mental health benefits. But as many as one in eight British households have no access to a garden or outdoor space of their own.

This issue is particularly pronounced among city dwellers, ethnic minorities and young people. A 2021 survey conducted in England revealed that those aged 16-24 were more than twice as likely to lack access to a garden or allotment compared to those aged over 65.

Quarter life, a series by The Conversation

This article is part of Quarter Life, a series about issues affecting those of us in our twenties and thirties. From the challenges of beginning a career and taking care of our mental health, to the excitement of starting a family, adopting a pet or just making friends as an adult. The articles in this series explore the questions and bring answers as we navigate this turbulent period of life.

You may be interested in:

How community gardening could ease your climate concerns

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Guerrilla gardening is a particularly good option for these groups of people. It can involve planting herbs or vegetables for a whole community to enjoy, spreading seeds or plants, tidying weeds, or even something as simple as picking up litter.

But if you’re considering becoming a guerilla gardener, it’s important to understand your rights. Could you be arrested for it? And should you wait until after dark?

Can you be prosecuted?

It’s important to remember that much of the unused or abandoned land that is potentially suitable for guerilla gardening in towns and cities throughout the UK is owned by local councils. Common examples of such locations include broken pavements with missing slabs, wasteland and the central areas of roundabouts.

Although much of this land is already open for the public to walk over, actively gardening on it would become an act of trespass.

The law of trespass sounds scary. However, gardening on this land would be a breach of civil law rather than a crime. This means that most guerrilla gardeners are unlikely to receive a fine or a criminal record.

Landowners do have the legal right to use “reasonable force” to remove trespassers from their land. But, fortunately, it seems most councils have ignored guerrilla gardeners, having neither the time, money or inclination to bring legal action against them.

Colchester Council, for example, were unable to track down the identity of the “human shrub”, a mysterious eco-activist who restored the flowers in the city’s abandoned plant containers in 2009. The shrub returned again in 2015 and sent a gift of seeds to a local councillor.

In other areas of the UK, the work of guerilla gardeners has been cautiously welcomed by local councils. In Salford, a city in Greater Manchester, there is a formal requirement to submit an application and obtain permission to grow on vacant spots in the city. But the local authority tends not to interfere with illegal grow sites.

There seems to be an unwritten acceptance that people can garden wherever they want, given the abundance of available space and the lack of active maintenance. This also offers the additional advantage of saving both time and money for the local council.

You should still be careful about where you trespass though. In some areas, guerrilla gardening can lead to unwelcome attention. During the May Day riots of 2000, for example, guerrilla gardeners were accused of planting cannabis seeds in central London’s Parliament Square.

Gardening at night may draw the wrong attention too, particularly if you are carrying gardening tools that might be misunderstood by the police as threatening weapons.

How can you start?

There are many different types of guerrilla gardening that you could get involved in, from planting native plant species that benefit pollinators and other wildlife to tidying derelict land to create safer places for the local community.

One of the simplest forms of guerilla gardening is planting seeds. Some environmental projects circulate “seed bombs” and others use biodegradable “seed balloons” that are filled with helium and deflate after a day, distributing seeds by air.

Whatever you try, as a guerrilla gardener you shouldn’t harm the environment or spoil other people’s enjoyment of the space around you. Remember that weeds and wilderness have an environmental value too. And think carefully about the species you are going to plant so that you can protect local plants and wildlife.

A man dropping a seed bomb on the ground in front of a grey building.
Some projects circulate seed bombs. Miriam Doerr Martin Frommherz/Shutterstock

The most attractive species to humans might not provide the best home or food for wildlife. Some can even outcompete native plants and drive them towards extinction. Planting certain harmful, invasive or poisonous species like ragwort, knotweed or Himalayan balsam is even prohibited by law.

That said, some guerrilla gardeners have used social media to organise “balsam bashing” events, where people come together to pull up this harmful invasive plant.

Guerrilla gardening takes many forms and can bring great benefits for people and the environment. You’re unlikely to be arrested for planting and growing trees and other greenery in public spaces. But remember that these spaces should be shared with everyone, including your local wildlife.

Ben Mayfield does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.

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Fractyl Health’s GLP-1 gene therapy spurs 25% weight loss in obese mice, clinical trials slated for 2024

One of the biggest problems facing the burgeoning class of weight loss drugs is that people must take them day after day, week after week. When the injections…



One of the biggest problems facing the burgeoning class of weight loss drugs is that people must take them day after day, week after week. When the injections of semaglutide — the ingredient in Ozempic and Wegovy — stop coming, so do the benefits. Lost weight is regained.

But researchers at Fractyl Health, a Lexington, MA-based biotech, believe they have a solution to that problem: a one-time gene therapy injected into the pancreas that lets the body make its own GLP-1 agonists in perpetuity.

New data slated to be presented today at a diabetes conference in Germany suggest that obese mice injected with the therapy lost nearly 25% of their body weight after just two weeks, according to a copy of the company’s presentation obtained by Endpoints News.

The results leave many questions unanswered, including how safe and effective the approach will be beyond the first two weeks, although the presentation indicated that such studies are ongoing. Fractyl declined requests for an interview.

The company previously announced plans to begin testing the treatment in people with diabetes and obesity in 2024. It’s a bold step towards moving gene therapy beyond the rare diseases typically pursued by biotech companies.

Randy Seeley

“It’s hard to get people to take injections once a week, and if we can figure out how to do something closer to one and done, that would be a big step for patients,” Randy Seeley, who directs an obesity research center at the University of Michigan School of Medicine, told Endpoints in an interview.

“But how permanent this will be can’t really be answered in a mouse,” he added. Seeley is a consultant to Fractyl, and the company supports research in his lab.

Fractyl was originally just developing the GLP-1 gene therapy for type 2 diabetes. In a diabetic mouse model, human pancreatic islets and human beta cell lines, the treatment significantly enhanced glucose-stimulated insulin secretion, improving blood sugar levels.

GLP-1 needs to act on receptors in the brain for its weight loss effects, and since the therapy is injected directly into the pancreas, the company didn’t expect the diabetic mice would lose weight, Seeley said. But surprisingly, they did, shedding 23% of their mass after four weeks compared to a control group.

Those results spurred the company to test its gene therapy in a diet-induced obesity mouse model. Twenty mice were fed a high fat diet for 25 weeks before half of them got a single injection of the gene therapy while the other half received daily injections of semaglutide.

Both groups of mice began losing weight a day after the injections. Within five days, the mice who got the gene therapy were losing weight faster and shed 24.8% of their body weight after just two weeks, even as they maintained their high fat diet. The mice on semaglutide lost 18.4% of their weight, according to the data presented at the European Association for the Study of Diabetes Scientific Congress.

“The most surprising part of the data is how much weight these animals lose,” Seeley said. “it’s better than semaglutide, and it’s not exactly clear how that occurs.”

Given the uncertain long-term effects of taking GLP-1 drugs for weight loss, a potentially permanent gene therapy approach is sure to raise many questions.

“If you’re taking your once-a-week version, if something goes wrong, we can turn it off and we just take it away,” Seeley said. “But with gene therapy, there’s no way to turn it off. It’s unknown what happens, and so it is going to take both some careful thought.”

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Trans To Be Banned From Female Hospital Wards In UK

Trans To Be Banned From Female Hospital Wards In UK

Authored by Steve Watson via Summit News,

The UK Health Secretary is to issue a proposal…



Trans To Be Banned From Female Hospital Wards In UK

Authored by Steve Watson via Summit News,

The UK Health Secretary is to issue a proposal to ban trans patients from female hospital wards in the UK, as well as reinstating ‘sex specific’ language in National Health Service materials, according to reports.

The Daily Mail reports that “Steve Barclay will unveil the plans to push back against ‘wokery’ in the health service amid concerns that women’s rights are being sidelined.”

The proposal would see only people of the same biological sex sharing wards, with care coming from doctors and nurses of the same sex, when it comes to intimate health matters.

“We need a common-sense approach to sex and equality issues in the NHS. That is why I am announcing proposals for clearer rights for patients,” Barlcay stated, adding “It is vital that women’s voices are heard in the NHS and the privacy, dignity and safety of all patients are protected.”

He added “And I can confirm that sex-specific language has now been fully restored to online health advice pages about cervical and ovarian cancer and the menopause.”

As we previously highlighted, the word ‘women’ was removed from such materials and replaced with non-gendered terms to be “more inclusive”:

A source close to the Health Secretary told the Telegraph that “The Secretary of State is fed up with this agenda and the damage it’s causing, language like “chestfeeding”, talking about pregnant “people” rather than women. It exasperates the majority of people, and he is determined to take action.”

“He is concerned that women’s voices should be heard on healthcare and that too often wokery and ideological dogma is getting in the way of this,” the source added.


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