type 1 and P fimbriae of uropathogenic Escherichia coli, the major causative agent of urinary tract infections in humans.
A way has been found to stop deadly bacteria from infecting patients. The discovery could lead to a whole new way of treating antibiotic-resistant ‘superbugs’. The Austalian researchers have uncovered what may be an Achilles heel on the bacteria cell membrane that could act as a potential novel drug target. Almost every second woman suffers from a urinary tract infection, UTI during her lifetime, mostly caused by E. coli. It travels along the urethra to the bladder where it triggers painful infections.
In order to infect the bladder (which is constantly being flushed out with urine), the bacteria have developed nanofilaments which effectively anchor the bacteria to the walls of the urinary tract. A team headed by Professor Trevor Lithgow, Monash University, has found a protein – called the TAM – that is crucial to the assembly of these anchoring filaments. The researchers describe how they developed an assay to measure the assembly of the filament forming protein, called usher.
“Using our assay we tested whether blocking TAM had any effect on usher. What we found was that TAM is required for the assembly of usher and therefore for production of the filaments needed to anchor the bacteria to the urinary tract surface,” he said. The assay revealed that, under normal circumstances, E. coli can create filaments within 2 minutes of sensing the urinary tract environment. However, when TAM is blocked, it can take up to 4 hours for the same anchoring process to happen.
This dscovery could be a very important target for drug therapy. “Most antibiotics against E. coli have to get across the bacterial cell membranes in order to kill the invader,” he said. “The TAM is on the bacterial surface, so it is directly accessible to the sorts of drugs that would inhibit its function, and thereby halt the rapid production of these nanofilaments.”
Importantly, other potentially lethal bacteria also use filaments which are controlled through TAM. These include Klebsiella pneumoniae carbapenemase-producing bacteria (KPC) which caused a scare in Victoria last year when Victorian authorities issued an alert that the antibiotic resistant superbug may have contributed to up to 18 deaths over the previous 3 years. http://www.eurekalert.org/pub_releases/2016-05/mu-ep051616.php
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