Identification of point mutations in clinical Staphylococcus aureus strains that produce small-colony variants auxotrophic for menadione.
Staphylococcus aureus small-colony variants (SCVs) are implicated in chronic and relapsing infections that are difficult to diagnose and treat. Despite many years of study, the underlying molecular mechanisms and virulence effect of the small-colony phenotype remain incompletely understood. We sequenced the genomes of five S. aureus SCV strains recovered from human patients and discovered previously unidentified nonsynonymous point mutations in three genes encoding proteins in the menadione biosynthesis pathway. Analysis of genetic revertants and complementation with wild-type alleles confirmed that these mutations caused the SCV phenotype and decreased virulence for mice.
Center for Molecular and Translational Human Infectious Diseases Research, Houston Methodist Research Institute, Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas, USA.
Melissa A
MA
Dean
Randall J
RJ
Olsen
S Wesley
SW
Long
Adriana E
AE
Rosato
James M
JM
Musser
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D004195:Disease Models, Animal; D016680:Genome, Bacterial; D005839:Gentamicins / Q000494:pharmacology; D051379:Mice; D008826:Microbial Sensitivity Tests; D010641:Phenotype; D017354:Point Mutation; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D013203:Staphylococcal Infections / Q000235:genetics / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D014774:Virulence / Q000235:genetics; D024483:Vitamin K 3 / Q000378:metabolism
D000900:Anti-Bacterial Agents; D005839:Gentamicins; D024483:Vitamin K 3