Antibiotic resistance: Sheffield scientists discover new drug combination to tackle antimicrobial resistance

• Breakthrough study involving University of Sheffield academics demonstrates a new approach to the global health crisis of antibiotic resistance
• Experts discover a new combination of antimicrobial compounds that can kill multi-drug resistant bacteria
   

Scientists at the University of Sheffield have demonstrated how a novel combination of drugs could be used to treat infections caused by multi-drug resistant bacteria.

The new research conducted by Professor Robert Poole and Dr Namrata Rana at the University of Sheffield in collaboration with research partners at the University of Surrey and the University of Würzburg, Germany, explored the use of metal complexes as adjuvants to traditional antibiotics that have become ineffective.

Antimicrobial resistance (AMR) is one of the biggest threats to global health. AMR occurs when a bacterium makes antibiotics ineffective. AMR occurs naturally but the misuse of antibiotics in humans and animals is accelerating the process.

The study published in the journal, Microbiology, revealed that the "antibiotic of last resort", colistin, was significantly more effective against a multi-drug resistant Escherichia coli when combined with a triacarbonyl manganese molecule, developed by the University of Würzburg.

The University of Surrey have extended this study, funded by a collaborative Research Council grant, and published in PLoS One. Using a large panel of other strains of multi-drug resistant bacteria, they confirmed Sheffield's findings. Additionally, they found survival rates of 87 per cent in an insect model of infection, when treated with a combination of triacarbonyl manganese molecule and the antibiotic, compared to a 50 per cent survival rate of those given only colistin.

Head author of the study, Professor Robert Poole from the University of Sheffield's Department of Molecular Biology and Biotechnology said: "For many years we have been developing an understanding of the modes of action against pathogens of several metal complexes, but these results are particularly striking.

"Bacterial infections endanger human health worldwide, a threat that is compounded by the slow development of new antibiotics.

"We are approaching an apocalyptic 'post-antibiotic era'. In 2015, researchers identified bacteria resistant to colistin, a drug that is often considered the last resort, in patients and livestock in China."

To meet these ongoing challenges, numerous international initiatives on AMR have been launched, including a World Health Organisation (WHO) global action plan. One important approach is understanding how non-antibiotic antimicrobial agents act and could be used to help established antibiotics, like colistin. Antibiotics that are no longer effective could potentially be reactivated when used with this metal complex, providing medical professionals with more options in treating diseases.

Dr Hannah Southam, postdoctoral researcher from the University of Sheffield said: "Antimicrobial resistance is a global health problem. Public Health England estimates that 5,000 people die every year in England because antibiotics no longer work for some infections. The UK's Chief Medical Officer, Dame Sally Davies, has declared AMR as 'one of the greatest threats we face today'. One of the greatest concerns is that no new class of antibiotic has been developed for clinical use against Gram-negative bacteria like E. coli for over 40 years.

"The lack of antibiotic discovery and development is attributed to many factors such as the high costs incurred by pharmaceutical companies of bringing a new drug to market. Other factors include the limitations and restrictions in the deployment of any potential novel antimicrobial drug brought to market in the attempt to limit resistance to the new drug."

The study was funded by Biotechnology and Biological Sciences Research Council (BBSRC) and the Leverhulme Trust.

This research builds on the University of Sheffield's position at the forefront of world-class research into infectious diseases. Scientists at the University are developing radical solutions to the global threat of disease and antimicrobial resistance as part of signature research projects such as Florey, Imagine and the Sheffield Antimicrobial Resistance Network (SHAMROK).

The University is also training the next generation of highly skilled scientists through its undergraduate and postgraduate programmes to find exciting new approaches to bioscience and tackle some of the world's biggest biomedical problems.

Key facts about antimicrobial resistance (AMR)

• AMR is the ability of a microorganism to resist the effects of a previously effective antimicrobial agent
• The effect of AMR on antibiotics is a global health problem
• Public Health England estimates that 5,000 people die every year in England because antibiotics no longer work against some bacterial infections
• Worldwide, it is estimated that 700,000 people die every year because of multi-drug resistant infections – this figure is predicted to rise to 10 million a year by 2050

ATOMIC FORCE: Dr Muhammad Usman Ghori wins top conference award for ground-breaking drug analysis technique

Research on a ground-breaking new technique for drug analysis has earned University of Huddersfield scientist Dr Muhammad Usman Ghori the top award at an international conference.

Dr Ghori has been working on the use of an ultra-high resolution atomic force microscope (AFM) in order to carry out nano-scale chemical imaging of material surfaces.  

The technique – which has been patented – achieves greater accuracy and analytical power than existing methods of chemical mapping.

In 2015, Dr Ghori was declared Vice-Chancellor’s Research Student of the Year at the University of Huddersfield.  It was in recognition of his recently-completed doctoral thesis plus a sequence of articles covering issues that include oral-controlled drug delivery systems and various aspects of drug release behaviour.

Before he relocated to the UK and embarked on research at the University of Huddersfield, Dr Ghori had already been awarded a Doctor of Pharmacy degree in his native Pakistan.  He was awarded a scholarship to carry out PhD research at the University of Huddersfield, where his supervisor was the Head of Pharmacy, Professor Barbara Conway.  

After completing his PhD at the University of Huddersfield, Dr Ghori was appointed as a Research Fellow on a project to develop 3D nano-scale chemical imaging using AFM, working with Professor Mike Reading, a renowned scientist in thermal analysis and Professor Conway, who is an expert on pharmaceutical formulations.

When Dr Ghori attended the Atomic Force Microscope conference and User Meeting, held at University of Cambridge from 13-14 December 2016, he displayed a poster and presented a paper describing the nano-scale imaging technique he has assisted to develop.  The conference had 200 participants from around the world and all were invited to vote for the best poster presentation.

Dr Ghori came top of the poll and received a Platinum Award from conference organisers, Bruker Nano-surfaces UK. Researchers at the universities of Cambridge and Oxford took second and third places.

Million pound drug dealers jailed

Duo locked up after police seize huge haul of Class A drugs

Two Bradford men have been sentenced to over 16 years in prison after a massive drugs bust in the city in June.　

GUILTY: Kamran Hanif and Matthew Hurd were sentenced to 16 years in prison

Kamran Hanif, 35, of Sewell Road, and Matthew Hurd, 24, of Woodview Terrace, were both arrested on 17th June after an organised police operation.

After officers saw Hanif leave a property on Woodview Terrace and get into a taxi, they acted quickly to arrest him in the vehicle where they found him carrying 15 kg of heroin.

With an average purity of 55 per cent, the Class A drugs had an estimated street value of around £937,500.　

Following Hanif’s arrest, officers then returned to the property and saw Hurd running away.

He was later arrested in a nearby public house. Officers then searched the property and found 55kg of mixing agent worth £13,834 and 271g of Cannabis worth £2,810.　

Both men admitted, at Bradford Crown Court, a charge of Conspiracy to Supply Class A drugs.

DANGEROUS: Hanif was caught with 15kg of heroin on him when he was arrested in Bradford earlier this year

Hurd also admitted possession with intent to supply cannabis with the duo sentenced on Wednesday 7th December.

Detective Chief Inspector Warren Stevenson said the lengthy prison sentences handed out to both men should be a warning to other dealers in the city.

“The impact of drug dealing can be devastating, often being the catalyst for other offending and ripping the heart out of communities,” he said.

“I hope that the sentences passed to Hurd and Hanif reassures the public that we continue to be committed to tackling drug dealing across West Yorkshire, as well as a stark warning to those blighting our neighbourhoods by dealing drugs that we will do everything within our power to bring you to justice.”　

Anyone concerned about drug dealing in their area are asked to contact their local Neighbourhood Policing Team via 101.

101-years in jail for drug gang downed by West Midlands Police

A century behind bars

A drugs gang supplying heroin, cocaine and cannabis on an ‘industrial scale’ in Birmingham have been jailed for more than 100 years after West Midlands Police brought down their network.

Detectives uncovered drug safe houses, cannabis factories and an extensive chain of dealer phones allocated names such as ‘The T Line’ used to take orders and even issue text advertisements.

GUILTY: Shaymas Ulhaq was identified as the ‘kingpin’ of a sophisticated drug network in the West Midlands

Shaymas Ulhaq, from Weston Road in Handsworth, was identified as the kingpin who oversaw six cannabis grows – including one with a £150,000 yield operating from the back of a tyre firm in Erdington – and managed a group of drug runners and farmers.

When officers stopped the 32-year-old in a car on 22nd July 2014 he was wearing a diamond encrusted ring and a jewel-laden Audemars Piguet watch, while £1,000 in cash was found in one of his pockets.

He claimed to be a successful car dealer – but analysis of his phone showed regular contact with other numbers linked to the cartel including texts issuing orders and instructions showing he was directing the enterprise.

Other lead players in the network – which police proved had operated for at least 14 months from March 2014 to May 2015 – included Masoud Ali, Mohammed Rahman-Harries, brothers Narinder and Sandeep Kandola, Azim Thakur and Wayne O Connor.

Officers working on the case carried out a series of car stops and house raids netting drugs, dealer paraphernalia and tens of phones that were connected through shared messages relating to drug dealing and supply.

And at Birmingham Crown Court this week, 15 people were jailed for a total of 101 years for drug dealing, including an 18-year term for Ulhaq who was found guilty by a jury of conspiracy to supply heroin, cocaine and cannabis.

Detective Inspector Ben West, from West Midlands Police Force CID, said: “This was a sophisticated system of drug trafficking featuring a chain of command… it turned over hundreds of thousands of pounds in the space of 14 months.

“The judge commented that distribution of such drugs can have ‘catastrophic results’ and ruin countless lives.

“Ulhaq and his co-conspirators were making huge sums of money out of other people’s misery and flaunting that wealth. When Ulhaq was stopped he was wearing a watch valued in excess of what many hard-working people would fail to earn in a year.”