Taking the fight to deadly antibiotic-resistant bacteria

The (opens in a new window)World Health Organization (WHO) estimates that by 2050, there could be 50 million deaths annually due to antibiotic resistance. (opens in a new window)Professor Siobhán McClean is fighting to tackle some of these drug-resistant pathogens threatening so many lives. 

In the century since Alexander Fleming discovered the first antibiotic – penicillin – in 1928, the world has benefited from reductions in deaths from pneumonia, tuberculosis, and post-operative infections. Yet the power of antibiotics appears on the wane, as disease-causing bacteria evolve ways to avoid them. 

The implications are severe: commonly performed surgeries are becoming riskier, and cancer patients, in a weakened state, are increasingly vulnerable to infection during their chemotherapy. 
“There is a pressing need for alternative solutions”, said Professor McClean, who has spent her career fighting deadly bacteria. 

Cystic Fibrosis 

Professor McClean has long had an interest in the types of bacteria that infect people with cystic fibrosis (CF), a genetic disorder. In Ireland, there are about 1,400 adults and children living with CF, amounting to the highest prevalence in the world. 

When Prof. McClean set out on her scientific career, the prognosis for CF patients was grim with many people not surviving beyond their twenties. Since then, medical advances mean people with CF can live into their fifties by tackling the bacteria that threaten to negatively impact on the functioning of the lungs and other bodily organs. 

“As CF patients live longer, they face the ongoing threat of chronic infections that diminish their quality of life,” said Prof McClean.

When researching the bacteria that cause problems for people living with CF, Prof McClean noticed something intriguing. “The low oxygen environments of CF lungs make bacteria more resilient,” Prof McClean said. “The bacteria adapt to low oxygen environments by producing molecules that help them to survive. We are studying this process so that we can prevent the bacteria from adapting and so reduce chronic infections”   

Prof McClean pointed to a Danish study showing that hyperbaric oxygen therapy - where oxygen is put under more pressure than normal - reduces bacterial colonisation in CF. “While hyperbaric oxygen therapy is cumbersome it confirms the importance of targeting low oxygen in treating bacterial infections.” 

Non CF Bugs 

McClean's work extends beyond CF to several pathogenic threats identified by the WHO as critical priorities. These include Pseudomonas aeruginosa, a bacteria known for its ability to resist antibiotics and for being a factor causing serious illnesses such as ventilator associated pneumonia and sepsis. Her laboratory group are developing vaccines to protect against these infections. 

Another bacteria of interest to Prof McClean is Burkholderia pseudomallei. This causes melioidosis, a tropical infection that has a 40% mortality rate in parts of Southeast Asia. It is found in the soil and surface groundwater of many tropical regions and causes about 165,000 cases of melioidosis globally per year. 

Prof. McClean and her team developed a vaccine candidate for melioidosis a few years back. In 2022, (opens in a new window)Poolbeg Pharma signed an exclusive license agreement for it through NovaUCD, the hub of start-up and innovation related activities in University College Dublin.
This success is a potential lifeline for communities in Southeast Asia and Northern Australia, where this infection is endemic.

Prof. McClean spends a lot of time seeking funding, patenting her discoveries, and attracting interest from investors. This effort, she said, has been greatly helped by a recent initiative known as the (opens in a new window)Research Ireland Accelerating Research to Commercialisation (ARC) Hub. 

The goal of ARC hub is to support the translation of early-stage research into viable commercial opportunities, she said. UCD is co-leading the ARC Hub for Therapeutics with (opens in a new window)Trinity College Dublin and (opens in a new window)RCSI University of Medicine and Health Sciences.

Targets 

Prof. McClean aims to advance at least one vaccine into human trials in the next five to 10 years, while, in parallel, developing new therapies that target bacterial colonisation mechanisms. 

Vaccines don’t just prevent infections, said Prof. McClean, but they can also tackle the rise of antibiotic resistance. By employing targeted vaccine components, she is aiming to train our immune system to recognise and combat specific bacterial pathogens.

Even though antibiotics may be on the wane, Prof. McClean still sees a role for them in future infection control. “We’ll possibly use vaccines and antibiotics in tandem. Vaccines can stimulate the immune system, which will weaken the bacteria so that they are more susceptible to antibiotics.” 

There are also bacteria that are hard to treat once they infect someone so the goal must be to prevent infection. 
“We want to prevent infections by using vaccines and also develop therapeutic vaccines for the hard-to-treat bacterial infections.” 

The success of Prof McClean’s work against infectious diseases in future is something we all have a stake in, as each breakthrough saves lives, reduces suffering and fortifies our healthcare system. 

In conversation with journalist, Sean Duke