We are aiming to understand the mechanisms and structures of multidrug transporters.
Antibiotics, which literally means “against life”, were originally produced by bacteria or
fungi. They are used to attack the specific agent causing the infection, hence helping
the infected host to eliminate the infection. However, extensive use of antibiotics has
raised a serious public health problem due to multidrug resistance, in which bacteria
become resistant to multi-antibiotics.To combat diseases caused by multidrug resistant bacteria, we need to learnmore about the physiology of pathogens to aid in
new drugs and extend the life of antibiotics.
MacA, a membrane fusion protein (MFP), MacB, an inner membrane protein (IMP) and
TolC, an outer membrane protein (OMP), form a tripartite pump to transport macrolide
drugs across the inner and outer membranes, one of the factors to multidrug resistance
in bacteria. The elucidation of dynamics of the assembly of the tripartite pump helps understand how it transports drugs and toxins out of the cell, a requisite for the
rational design of inhibitors that block the pump or its assembly.
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2. Lin HT, Bavro VN, Barrera NP, Frankish HM, Velamakanni S,van Veen HW,
Robinson CV, Borges-Walmsley MI, Walmsley AR.MacB ABC transporter is a dimer
whose ATPase activity and macrolide-binding capacity are regulated by the membrane
fusion protein MacA. J Biol Chem. 2009 Jan 9;284(2):1145-54. (SCI)