Alteration of Streptococcus pneumoniae membrane properties by the folate analog methotrexate.
The antifolate compound methotrexate (MTX) is toxic to the gram-positive bacterium Streptococcus pneumoniae. Interaction of MTX with this bacterium resulted in an increase in the electric transmembrane potential (delta psi) and enhanced the delta psi-dependent uptake of isoleucine and MTX. In contrast, delta psi-independent uptake of glutamine was not changed. Folate, a nontoxic analog of MTX, did not exhibit these membrane effects, nor did it prevent the effect of MTX, suggesting that the NH2 in position 4 of the pteridine ring of the MTX molecule is involved in the MTX response. A strain bearing the nonsense mutation amiA9, selected for MTX resistance, did not exhibit increased membrane potential after MTX pretreatment. This suggests that MTX interacts with a specific membrane component in S. pneumoniae. A resulting change in ion permeability could lead to changes in the magnitude of the delta psi. The MTX-sensitive component is altered or absent in mutant amiA9.
D001692:Biological Transport / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D007532:Isoleucine / Q000378:metabolism; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D008727:Methotrexate / Q000378:metabolism / Q000494:pharmacology*; D009154:Mutation; D013045:Species Specificity; D013296:Streptococcus pneumoniae / Q000187:drug effects / Q000378:metabolism*
D007532:Isoleucine; D005973:Glutamine; D008727:Methotrexate