Contribution of β-lactamase production to the resistance of mycobacteria to β-lactam antibiotics

Mycobacterium fallax (M. fallax) is naturally sensitive to many β-lactam antibiotics (MIC <2 μg/ml) and devoid of β-lactamase activity. In this paper, we show that the production of the β-lactamase of Mycobacterium for fortuitum by Mf. fallax significantly increased the MIC values for good substrates of the enzyme, whereas the potency of poor substrates or transient inactivators was not modified. The rates of diffusion of β-lactams through the mycolic acid layer mere low, but for all studied compounds the half-equilibration times mere such that they would only marginally affect the MIC values in the absence of β-lactamase production. These results emphasize the importance of enzymatic degradation as a major factor in the resistance of mycobacteria to penicillins.