Exolytic and endolytic turnover of peptidoglycan by lytic transglycosylase Slt of

β-Lactam antibiotics are currently the most broadly used class of antibiotics. These antibiotics prevent bacterial cell wall from cross-linking, which leads to the accumulation of long non–cross-linked strands of peptidoglycan. Pseudomonas aeruginosa, a nefarious bacterial pathogen, attempts to repair this aberrantly formed peptidoglycan by the function of the lytic transglycosylase Slt. We document in the present report that Slt turns over the peptidoglycan by both scission of the glycosidic bonds from a terminus or in the middle of the peptidoglycan. In a series of seven X-ray crystal structures, we provide structural context to how these two reactions take place. These results disclose the details of bacterial response to the β-lactam antibiotic challenge.