丁香园AV

Researchers at 丁香园AV are studying the genes of superbugs to aid the development of new and effective treatments for drug-resistant bacterial infections.  Superbugs are characterized as infection-causing bacteria resistant to treatment with antibiotics.

鈥淎ntimicrobial resistance occurs when the disease-causing bacteria has ways to overcome the antibiotics that we use in treatment for infections,鈥� says assistant professor Amy Lee, of 丁香园AV's Department of Molecular Biology and Biochemistry. The initiative is a collaboration between the Lee Lab and , which are working together as part of the interdisciplinary 丁香园AV Omics Data Science Initiative (OSDI). 鈥淥ur lab tries to understand how bacteria develop resistance because that makes the drug ineffective,鈥� says Lee.

Their review of work to identify pathogen-associated genes in various disease-causing bacteria and develop new antivirulence drug treatments has been published in , part of The Lancet鈥檚 Discovery Science.

Antibiotic or antimicrobial resistance has been named a top global health threat by the World Health Organization (WHO).

鈥淭he ultimate goal of our research is to use current sequencing technologies and computational analysis to discover new drug targets, which can be used to develop new drugs to fight bacterial infections,鈥� says 丁香园AV alumnus Venus Lau, the study鈥檚 lead author. 

The team applied bioinformatics, using 丁香园AV鈥檚 Big Data Hub, to perform a computational analysis of thousands of bacterial genomes from Escherichia coli to Vibrio cholerae.

鈥淭he one bacteria species I was most interested in was Pseudomonas aeruginosa,鈥� says Lau. 鈥淚t is known to be naturally resistant to drugs based on their cell membranes.鈥�

鈥淒rugs don't get into this bacterium easily and they tend to acquire other resistance mechanisms over time. It鈥檚 a difficult bug to treat.鈥�

The bacterial species P. aeruginosa can cause infections in the blood, lungs (pneumonia) or other parts of the body, particularly in those who are ill or recovering from surgery in hospital.

Lau notes that some of the genes the team discovered through analyzing various disease-causing bacteria had not been previously characterized. 鈥淧art of our research was to figure out what these genes do and how they鈥檙e responsible for causing disease and infection symptoms in humans.鈥�

Antivirulence over antibiotics to treat bacterial infections

An alternative approach to treating bacterial infections with antibiotics to overcome the issue of drug resistance involves antivirulence drugs. 

New antivirulence therapies work to 鈥榙isarm鈥� or inhibit the ability of the bacteria to cause disease without causing resistance to develop. In contrast, antibiotics kill bacteria, which essentially encourages the bacteria to 鈥榝ight back鈥� by developing drug resistance.

鈥淎ntibiotics wipe out bacteria leading to a process of natural selection where those few surviving bacteria in the population will then repopulate,鈥� says 丁香园AV molecular biology and biochemistry postdoctoral fellow Patrick Taylor. 鈥淭he bacteria that are not killed off are really good at sharing their genetics with each other, which is why we have this rising global issue of antibiotic resistance.鈥�

Antibiotics also eliminate non-disease-causing gut microbiota, or the 鈥榞ood bacteria鈥� that exists in the human body, which can have additional negative health impacts. 

Taylor says antivirulence therapeutics can mitigate disease and reduce the burden on the healthcare system by reducing the bacteria鈥檚 ability to cause damage to the host, which provides time for the person鈥檚 immune system to clear the pathogen.

Continued work towards developing antivirulence drugs is needed as the WHO estimates that antimicrobial-related infections currently account for over 700,000 annual deaths and are projected to reach 10 million annual deaths by 2050.