β-Lactam antibiotics resistant to β-lactamase degradation can be produced by many chemical modifications, but often at the expense of antibacterial activity. Substitution onto several positions in the molecule produces different and often selective resistance; for instance, heavily sterically hindered acyl groups give staphylococcal P-lactamase resistance to penicillins, and resistance to some enzymes from Gram-negative pathogens to both penicillins and cephalosporins. 6-α- or 7-α-substituents respectively confer a broad spectrum of resistance (e.g. cefoxitin), but changes at positions 2 or 3 have only a minor influence on enzyme susceptibility. Changes in the ring condensed with the β-lactam, such as changing ceph-3-em to ceph-2-em may greatly enhance stability. Small improvements can occur when the nuclear sulphur atom is oxidized, but a much better effect is obtained when it is replaced by another atom such as oxygen, as in clavulanic acid. This compound appears to have broad spectrum resistance which is actually due to susceptibility and subsequent product inhibition.
Novel gene Sen2 conferring broad-spectrum resistance to Synchytrium endobioticum mapped to potato chromosome XI
