Urinary tract infections are both very common and potentially very dangerous. More than half of all Australian women will suffer from a UTI in their lifetime, and nearly one in three women will have an infection requiring treatment with antibiotics before the age of 24.
Uropathogenic E. coli filaments expressing Green Fluorescent Protein (GFP) after exfoliation from bladder cells, captured using epi fluorescence microscopy. Credit: Australian Institute for Microbiology and Infection, UTS
Around 80 per cent of UTIs are caused by uropathogenic E. coli (UPEC), which is increasingly resistant to antibiotics. E. coli-related death due to antimicrobial resistance is the leading cause of bacterial fatalities worldwide.
In a bid to aid discovery of new treatment options, researchers at the University of Technology Sydney (UTS) are using state-of-the-art microscopy to pinpoint how these bacteria spread and multiply.
Dr Bill Söderström and Associate Professor Iain Duggin, of the Australian Institute for Microbiology and Infection at UTS, said their latest research examined the shapeshifting behaviour of UPEC. During a UTI infection cycle, the bacteria form spaghetti-like filaments hundreds of times their normal lengths before reverting to their original form.
The study, which is published in Nature Communications, used a human bladder cell infection model to generate the filaments, and look at their reversal back to rod shape.
By giving the first clues into how the reversal of filamentation is regulated during infection, we may be laying the foundation for identifying new ways to combat UTIs.
Dr Bill Söderström
“While we don’t fully understand why they do this extreme lifestyle make-over, we know they must revert to their original size before they can reinfect new bladder cells,” Dr Söderström said.
“We used advanced microscopy to follow two key cell division proteins and their localisation dynamics during reversal. We found that the normal rules for regulation of cell division in bacteria does not fully apply in filaments,” Dr Söderström said.
“By giving the first clues into how the reversal of filamentation is regulated during infection, we may be laying the foundation for identifying new ways to combat UTIs.”
The devastating eruption of these bacteria from the cells of the bladder probably contributes to the extensive damage and pain experienced during a UTI.
Associate Professor Iain Duggin
Associate Professor Duggin said the long filaments formed by the bacteria appeared to break open the infected human cells, through a previously unknown mechanism called infection-related filamentation (IRF).
“The devastating eruption of these bacteria from the cells of the bladder that they invade probably contributes to the extensive damage and pain experienced during a UTI,” Associate Professor Duggin said.
“Our goal is to identify why and how the bacteria do this remarkable feat in the hope of enabling alternative treatments or preventions.”
The paper Assembly dynamics of FtsZ and DamX during infection-related filamentation and division in uropathogenic E. coli is published by Nature Communications. Authors are Bill Söderström, Matthew J. Pittorino, Daniel O. Daley and Iain G. Duggin.
FACTS ABOUT URINARY TRACT INFECTIONS
● Around 250,000 Australians develop a UTI each year
● Aboriginal and Torres Strait Islander people are at higher risk of UTIs
● Around 50-60 per cent of all women will have a UTI during their lifetime
● One in four women who have had a UTI will experience another within 12 months
● Nearly 1 in 3 women will develop a UTI that needs treatment with antibiotics before the age of 24
● More than one course of antibiotics is often needed due to increased antibiotic resistance in bacteria
● Urinary tract infections acquired in hospital (eg, through catheters) account for 380,000 extra hospital bed days a year
● Complicated UTIs have a mortality rate as high as one in three