Mycobacterial porins--new channel proteins in unique outer membranes.
Mycobacteria protect themselves with an outer lipid bilayer, which is the thickest biological membrane hitherto known and has an exceptionally low permeability rendering mycobacteria intrinsically resistant to many antibiotics. Pore proteins spanning the outer membrane mediate the diffusion of hydrophilic nutrients. Mycobacterium tuberculosis possesses at least two porins in addition to the low activity channel protein OmpATb. OmpATb is essential for adaptation of M. tuberculosis to low pH and survival in macrophages and mice. The channel activity of OmpATb is likely to play a major role in the defence of M. tuberculosis against acidification within the phagosome of macrophages. MspA is the main porin of Mycobacterium smegmatis. It forms a tetrameric complex with a single central pore of 10 nm length and a cone-like structure. This structure differs clearly from that of the trimeric porins of Gram-negative bacteria, which form one 4 nm long pore per monomer. The 45-fold lower number of porins compared to Gram-negative bacteria and the exceptional length of the pores are two major determinants of the low permeability of the outer membrane of M. smegmatis for hydrophilic solutes. The importance of the synergism between slow transport through the porins and drug efflux or inactivation for the development of drugs against M. tuberculosis is discussed.
Niederweis
Michael
M
Lehrstuhl für Mikrobiologie, Friedrich-Alexander-Universität Erlangen-Nürnberg, Staudtstr. 5, 91058 Erlangen, Germany. mnieder@biologie.uni-erlangen.de
D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002463:Cell Membrane Permeability; D006863:Hydrogen-Ion Concentration; D008264:Macrophages; D051379:Mice; D009161:Mycobacterium / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020102:Mycobacterium smegmatis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D018272:Porins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011487:Protein Conformation
D001426:Bacterial Proteins; C113302:OmpATb protein, Mycobacterium tuberculosis; D018272:Porins; C121838:mspA protein, Mycobacterium smegmatis