Lytic Transglycosylase Deficiency Increases Susceptibility to β-lactam Antibiotics But Reduces Susceptibility to Vancomycin in Escherichia coli

In Staphylococcus aureus, a gram-positive pathogen, vancomycin-resistant strains become susceptible to β-lactam antibiotics, referred to as the “seesaw effect.” However, in gram-negative bacteria, the phenomenon is less clear. Here, we analyzed the gene-knockout effects of eight lytic transglycosylases (slt, mltA, mltB, mltC, mltD, mltE, mltF, mltG) on antibiotic sensitivity in Escherichia coli. Knockout of both slt and mltG increased sensitivity to β-lactam antibiotics and reduced sensitivity to vancomycin. The β-lactam antibiotic sensitivity and vancomycin resistance of the slt-knockout mutant were abolished by the introduction of the wild-type slt gene but remained unchanged by the introduction of the mutant slt gene encoding an amino acid substitution variant of the transglycosylase catalytic centre. The double-knockout strain for slt and mltB was more sensitive to ampicillin and more resistant to vancomycin than each single-knockout strain. The double-knockout strain for slt and mltG was more sensitive to ampicillin and more resistant to vancomycin than each single-knockout strain. These results suggest that loss of lytic transglycosylase activity causes β-lactam antibiotic sensitivity and vancomycin resistance in E. coli.