Staphylococcus aureus menD and hemB mutants are as infective as the parent strains, but the menadione biosynthetic mutant persists within the kidney.
Small colony variants (SCVs) of Staphylococcus aureus were generated via mutations in menD or hemB, yielding menadione and hemin auxotrophs, respectively, and studied in the rabbit endocarditis model. No differences in the 95% infectious dose occurred between strains with regard to seeding heart valves ( approximately 10(6) cfu) or other target organs. No differences were observed between the response of the hemB mutant to oxacillin therapy and that of the parent strain in any target tissues, and significant reductions in bacterial densities were seen in all tissues (compared with untreated controls). In contrast, oxacillin therapy did not significantly reduce bacterial densities of the menD mutant in either kidney or spleen and significantly reduced densities within vegetations. These data show that SCVs are able to colonize multiple tissues in vivo and that the menD mutation provides the organism with a survival advantage during antimicrobial therapy, compared with its parent strain, in selected target tissues.
Department of Medical Microbiology and Immunology, University of Wisconsin Medical School, Madison, Wisconsin 53706, USA.
Donna M
DM
Bates
Christof
C
von Eiff
Peter J
PJ
McNamara
Georg
G
Peters
Michael R
MR
Yeaman
Arnold S
AS
Bayer
Richard A
RA
Proctor
D000818:Animals; D001798:Blood Proteins / Q000494:pharmacology; D004195:Disease Models, Animal; D024881:Drug Resistance, Bacterial; D004697:Endocarditis, Bacterial / Q000382:microbiology; D005260:Female; D005798:Genes, Bacterial / Q000235:genetics*; D007668:Kidney / Q000382:microbiology*; D008297:Male; D008826:Microbial Sensitivity Tests; D009154:Mutation; D010068:Oxacillin / Q000494:pharmacology; D010406:Penicillins / Q000494:pharmacology; D011817:Rabbits; D013203:Staphylococcal Infections / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects / Q000235:genetics* / Q000472:pathogenicity / Q000502:physiology*; D013997:Time Factors; D024483:Vitamin K 3 / Q000378:metabolism*
D001798:Blood Proteins; D010406:Penicillins; C077150:platelet microbicidal protein, Oryctolagus cuniculus; D024483:Vitamin K 3; D010068:Oxacillin