Article

MprF-mediated biosynthesis of lysylphosphatidylglycerol, an important determinant in staphylococcal defensin resistance.

Cellular and Molecular Microbiology, Medical Microbiology Department, University of Tübingen, Elfriede-Aulhorn-Str. 6, D-72076 Tübingen, Germany.
FEMS Microbiology Letters (impact factor: 2.04). 03/2004; 231(1):67-71. DOI:10.1016/S0378-1097(03)00921-2 pp.67-71
Source: PubMed

ABSTRACT Frequently bacteria are exposed to membrane-damaging cationic antimicrobial molecules (CAMs) produced by the host's immune system (defensins, cathelicidins) or by competing microorganisms (bacteriocins). Staphylococcus aureus achieves CAM resistance by modifying anionic phosphatidylglycerol with positively charged L-lysine, resulting in repulsion of the peptides. Inactivation of the novel S. aureus gene, mprF, which is found in many bacterial pathogens, has resulted in the loss of lysylphosphatidylglycerol (L-PG), increased inactivation by CAM-containing neutrophils, and attenuated virulence. We demonstrate here that expression of mprF is sufficient to confer L-PG production in Escherichia coli, which indicates that MprF represents the L-PG synthase. L-PG biosynthesis was studied in vitro and found to be dependent on phosphatidylglycerol and lysyl-tRNA, two putative substrate molecules. Further addition of cadaverin, a competitive inhibitor of the lysyl-tRNA synthetases, or of RNase A abolished L-PG biosynthesis, thereby confirming the involvement of lysyl-tRNA. This study forms the basis for further detailed analyses of L-PG biosynthesis and its role in bacterial infections.

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Keywords

abolished L-PG biosynthesis
 
attenuated virulence
 
bacterial infections
 
bacterial pathogens
 
CAM resistance
 
CAM-containing neutrophils
 
CAMs
 
competitive inhibitor
 
Escherichia coli
 
host's immune system
 
inactivation
 
L-PG
 
L-PG biosynthesis
 
L-PG production
 
L-PG synthase
 
lysyl-tRNA synthetases
 
membrane-damaging cationic antimicrobial molecules
 
modifying anionic phosphatidylglycerol
 
putative substrate molecules
 
study forms