Disarming disease-causing bacteria
New treatments to combat the problem of antibiotic resistance by disarming rather than killing bacteria may be coming soon, according to a recent study reported by Monash University, Australia.
Recent research (published in Nature Structure and Molecular Biology) showed that a protein complex called the Translocation and Assembly Module (TAM), formed a type of molecular pump in bacteria. The Translocation and Assembly Module allows bacteria to shuttle key disease-causing molecules from inside the bacterial cell where they are made, to the outside surface, priming the bacteria for infection.
Lead author Joel Selkrig of the Department of Biochemistry and Molecular Biology at Monash said the work paves the way for future studies to design new drugs that inhibit this process.
" The TAM was discovered in many disease-causing bacteria, from micro-organisms that cause whooping cough and meningitis, to hospital-acquired bacteria that are developing resistance to current antibiotics," said Selkrig.
" It is a good antibacterial target because a drug designed to inhibit TAM function would unlikely kill bacteria, but simply deprive them of their molecular weaponry, and in doing so, disable the disease process.
_ By allowing bacteria to stay alive after antibiotic treatment, we believe we can also prevent the emergence of antibiotic resistance, which is fast becoming a major problem worldwide."
The Monash team, led by Prof Trevor Lithgow from the Department of Biochemistry and Molecular Biology at Monash University, showed that the Translocation and Assembly Module is made of two protein parts, TamA and TamB, which function together to form a machine on a molecular scale. The researchers compared normal virulent bacteria with mutant strains of bacteria engineered to have no Translocation and Assembly Module.
" We noticed that proteins important for disease were missing in the outer membrane of the mutant bacteria," said lead author Joel Selkrig.
" The absent proteins help bacteria to adhere to our bodies and perform disease-related functions."
He added that the next step for the research group was to dissect the molecular mechanism of how the Translocation and Assembly Module complex functions and, in collaboration with researchers at the Monash Institute of Pharmaceutical Sciences, design an antibiotic that inhibits the Translocation and Assembly Module (TAM) in bacteria.
Prof Lithgow led an international team of Monash researchers, and scientists from the Melbourne University, Queensland University, Glasgow University (Scotland) and Birmingham University (England).
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Source: Monash University, Melbourne, Australia.