Altered lipid composition in Streptococcus pneumoniae cpoA mutants.
BACKGROUND
Penicillin-resistance in Streptococcus pneumoniae is mainly due to alterations in genes encoding the target enzymes for beta-lactams, the penicillin-binding proteins (PBPs). However, non-PBP genes are altered in beta-lactam-resistant laboratory mutants and confer decreased susceptibility to beta-lactam antibiotics. Two piperacillin resistant laboratory mutants of Streptococcus pneumoniae R6 contain mutations in the putative glycosyltransferase gene cpoA. The CpoA gene is part of an operon including another putative glycosyltransferase gene spr0982, both of which being homologous to glycolipid synthases present in other Gram-positive bacteria.


RESULTS
We now show that the cpoA mutants as well as a cpoA deletion mutant are defective in the synthesis of galactosyl-glucosyl-diacylglycerol (GalGlcDAG) in vivo consistent with the in vitro function of CpoA as α-GalGlcDAG synthase as shown previously. In addition, the proportion of phosphatidylglycerol increased relative to cardiolipin in cpoA mutants. Moreover, cpoA mutants are more susceptible to acidic stress, have an increased requirement for Mg(2+) at low pH, reveal a higher resistance to lysis inducing conditions and are hypersensitive to bacitracin.


CONCLUSIONS
The data show that deficiency of the major glycolipid GalGlcDAG causes a pleitotropic phenotype of cpoA mutant cells consistent with severe membrane alterations. We suggest that the cpoA mutations selected with piperacillin are directed against the lytic response induced by the beta-lactam antibiotic.
Marina
M
Meiers
Carsten
C
Volz
Jessica
J
Eisel
Patrick
P
Maurer
Bernhard
B
Henrich
Department of Microbiology, University of Kaiserslautern, Gottlieb-Daimler-Strasse, Gebäude 23, D-67663 Kaiserslautern, Germany. hakenb@rhrk.uni-kl.de.
Regine
R
Hakenbeck
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D055786:Gene Knockout Techniques; D016695:Glycosyltransferases / Q000235:genetics / Q000378:metabolism*; D050356:Lipid Metabolism; D008055:Lipids / Q000032:analysis*; D009154:Mutation; D010878:Piperacillin / Q000494:pharmacology; D013296:Streptococcus pneumoniae / Q000737:chemistry / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D018440:beta-Lactam Resistance
D000900:Anti-Bacterial Agents; D008055:Lipids; D016695:Glycosyltransferases; D010878:Piperacillin