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The high-glucose-induced cytotoxicity in diabetes has been widely recognized.  Staphylococcus aureus  is the most frequent pathogen isolated from diabetic foot ulcers, but the properties of this bacterium under high glucose conditions remain unclear.  S. aureus  grew in medium usually forms weak biofilm, and which was significantly increased by addition of glucose. However, extracellular DNA (eDNA), an important component of biofilms, was markedly decreased in presence of 15 mM glucose. The reduced eDNA content was not caused by degradation, because the nuclease activity of biofilm supernatants with glucose was significantly decreased due to the acidic pH of the medium. Under planktonic state, the growth of  S. aureus  was significantly decreased in the Luria-Bertani (LB) medium supplemented with 25 mM glucose, and the reduced growth of  S. aureus  by glucose was dose-dependent. Except for glucose, the growth of planktonic  S. aureus  was also markedly decreased by fructose or sucrose. Amounts of acid metabolites were produced under high glucose conditions, but the survival of planktonic  S. aureus  was unaffected by these acidic conditions. Cells of  S. aureus  from the culture medium with glucose had a thinner cell wall and highly resistant to lysostaphin compared with the bacteria cultured in LB medium. mRNA expression of genes encoding pentaglycine bridges, the substrate of lysostaphin, was significantly decreased in  S. aureus  by glucose. In addition to  S. aureus , the growth of  Staphylococcus haemolyticus  and  Staphylococcus epidermidis  was also significantly decreased by an excess of glucose, but strains of  Enterococcus faecalis ,  Escherichia coli , and  Pseudomonas aeruginosa  were unaffected by glucose. In conclusion, the reduced growth of  S. aureus  under high glucose conditions is due to impairment of the unique cell-wall structure, pentaglycine bridges.

Reduced Growth of Staphylococcus aureus Under High Glucose Conditions Is Associated With Decreased Pentaglycine Expression