The lytic transglycosilase Slt is critical in the cell wall recycling in Pseudomonas aeruginosa, as well in antibiotic resistance. Our structural work results disclose the details of bacterial response mediated by Slt to the b-lactam antibiotic challenge.

b-lactam antibiotics are currently the most used antibiotics. These antibiotics prevent bacterial cell wall formation, critical for bacterial survive. The cell wall contains the PG which is formed by alternated units of N-acetilglucosamine (NAG) and N-acetilmuramic acid (NAM) with peptide stems attached to NAM. These peptide stems are cross-linked creating a net. B-lactam antibiotics inhibit the transpeptidation process between peptides promoting the accumulation of aberrant long fragments. Pseudomonas aeruginosa attempts to repair this damage by the lytic transglycosilase Slt. In our work we have managed to solve the structure of the enzyme Slt to carry out the study of its catalytic mechanism getting several complexes with analogous of its natural substrate. Slt is able to degrade the PG through both endolytic (in the middle of chain) and exolytic (in one end) cut. Slt can accommodate the PG thanks to a long catalytic throat with up to 10 positions for NAG/NAM units together with certain key residues that interact with the peptide stems. These results disclose the details of bacterial response to the b-lactam antibiotic challenge. This work is a collaborative effort between the group of Juan A. Hermoso at “Rocasolano” Physical-Chemistry Institute and the group of Shahriar Mobashery at University of Notre Dame (USA).

Lee, M, Batuecas, M. T., Tomoshige, S., Domínguez-Gil, T., Mahasenan, K. V., Dik, D. A., Hesek, D., Millán, C., Usón, I., Lastochkin, E., Hermoso, J. A., Mobashery, S. Exolytic and Endolytic Turnover of Peptidoglycan by Lytic Transglycosylase Slt of Pseudomonas aeruginosaPNAS. DOI: 10.1073/pnas.1801298115

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