Impact of lgt mutation on lipoprotein biosynthesis and in vitro phenotypes of Streptococcus agalactiae.
Although Streptococcus agalactiae, the group B Streptococcus, is a leading cause of invasive neonatal disease worldwide the molecular basis of its virulence is still poorly understood. To investigate the role of lipoproteins in the physiology and interaction of this pathogen with host cells, we generated a mutant S. agalactiae strain (A909DeltaLgt) deficient in the Lgt enzyme and thus unable to lipidate lipoprotein precursors (pro-lipoproteins). The loss of pro-lipoprotein lipidation did not affect the viability of S. agalactiae or its growth in several different media, including cation-depleted media. The processing of two well-characterized lipoproteins, but not a non-lipoprotein, was clearly shown to be aberrant in A909DeltaLgt. The mutant strain was shown to be more sensitive to oxidative stress in vitro although the molecular basis of this increased sensitivity was not apparent. The inactivation of Lgt also resulted in changes to the bacterial cell envelope, as demonstrated by reduced retention of both the group B carbohydrate and the polysaccharide capsule and a statistically significant reduction (P=0.0079) in A909DeltaLgt adherence to human endothelial cells of fetal origin. These data confirm that failure to process lipoproteins correctly has pleiotropic effects that may be of significance to S. agalactiae colonization and pathogenesis.
Bray
Beverley A
BA
University of Bradford, West Yorkshire BD7 1DP, UK.
Sutcliffe
Iain C
IC
Northumbria University, Newcastle upon Tyne NE1 8ST, UK.
Harrington
Dean J
DJ
University of Bradford, West Yorkshire BD7 1DP, UK.
D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D042783:Endothelial Cells / Q000382:microbiology; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism*; D009154:Mutation; D018384:Oxidative Stress; D013290:Streptococcal Infections / Q000382:microbiology*; D013292:Streptococcus agalactiae / Q000201:enzymology* / Q000235:genetics / Q000502:physiology; D014166:Transferases / Q000235:genetics* / Q000378:metabolism
D001426:Bacterial Proteins; D008074:Lipoproteins; D014166:Transferases; C042308:phosphatidylglycerol glyceryl transferase