Vancomycin-intermediate Staphylococcus aureus strains have impaired acetate catabolism: implications for polysaccharide intercellular adhesin synthesis and autolysis.
The most common mechanism by which Staphylococcus aureus gains resistance to vancomycin is by adapting its physiology and metabolism to permit growth in the presence of vancomycin. Several studies have examined the adaptive changes occurring during the transition to vancomycin-intermediate resistance, leading to a model of vancomycin resistance in which decreased cell wall turnover and autolysis result in increased cell wall thickness and resistance to vancomycin. In the present study, we identified metabolic changes common to vancomycin-intermediate S. aureus (VISA) strains by assessing the metabolic and growth characteristics of two VISA strains (vancomycin MICs of 8 microg/ml) and two isogenic derivative strains with vancomycin MICs of 32 microg/ml. Interestingly, we observed the parental strains had impaired catabolism of nonpreferred carbon sources (i.e., acetate), and this impairment became more pronounced as vancomycin resistance increased. To determine if acetate catabolism impairment is common to VISA strains, we assessed the ability of VISA and vancomycin-sensitive S. aureus (VSSA) clinical isolates to catabolize acetate. As expected, a significantly greater percentage of VISA strains (71%) had impaired acetate catabolism relative to VSSA (8%). This is an important observation because staphylococcal acetate catabolism is implicated in growth yield and antibiotic tolerance and in regulating cell death and polysaccharide intercellular adhesin synthesis.
Nelson
Jennifer L
JL
Department of Veterinary and Biomedical Sciences, University of Nebraska, 155 VBS, East Campus Loop, Lincoln, NE 68583-0905, USA.
Rice
Kelly C
KC
Slater
Sean R
SR
Fox
Paige M
PM
Archer
Gordon L
GL
Bayles
Kenneth W
KW
Fey
Paul D
PD
Kreiswirth
Barry N
BN
Somerville
Greg A
GA
D000085:Acetates / Q000378:metabolism; D001433:Bacteriolysis; D008660:Metabolism; D011135:Polysaccharides, Bacterial / Q000096:biosynthesis*; D013045:Species Specificity; D013211:Staphylococcus aureus / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D014640:Vancomycin / Q000378:metabolism*; D020713:Vancomycin Resistance
D000085:Acetates; D011135:Polysaccharides, Bacterial; C113579:polysaccharide intercellular adhesin; D014640:Vancomycin