Effects of betaines and urine on the antibacterial activity of aminoglycosides.

Urine has long been known to inhibit the activity of aminoglycosides against urinary tract pathogens. Glycine betaine which is present in urine confers resistance against high osmolarity to Gram-negative organisms. We postulated that glycine betaine might contribute to the aminoglycoside resistance found in hypertonic urine. Escherichia coli became extremely resistant to gentamicin (40 x MIC in 0.9 M sodium chloride) when cultured in minimal medium supplemented with 10(-4) M glycine betaine and 0.1-1.0 M sodium chloride. Resistance was increased in the presence of high glucose concentrations but to a lesser extent (3 x MIC in 1.0 M glucose). This effect was not produced by other polyols or urea. These results suggest the observed synergism is mediated by the osmoprotective effects of glycine betaine and the inhibitory effect of sodium chloride or glucose against the aminoglycoside. Other betaines tested had a less marked effect. The betaines in urine permit the expression of increased resistance to aminoglycosides in concentrated urine.