Scientists from IQFR and the Univ of Notre Dame publish in the journal Nature Communications the structure of a key machinery in the process of bacterial division.

A team from the Spanish National Research Council (CSIC) and the University of Notre Dame (United States) has revealed the structure of a key machinery in the process of bacterial division. The conclusions, published in the latest issue of the journal Nature Communications, open the door to the design of a future drug capable of blocking this precise machinery, without which the bacteria become sensitive to the antibiotic effect. Virtually all bacterial species have specialized domains that recognize the bacterial wall (composed of peptidoglycan) at the time of division and allow the correct location in space and time of these proteins during the generation of the two daughter cells from the mother cell. Such is the case of SPOR domains, which are widely present in bacterial proteins that recognize cell-wall peptidoglycan strands stripped of the peptide stems (called "naked" glycans). This type of peptidoglycan is enriched in the septal ring as a product of catalysis by cell-wall amidases that participate in the separation of daughter cells during cell division.
The authors document the binding of synthetic naked glycans to the SPOR domain of the RlpA lytic transglycosylase of Pseudomonas aeruginosa (SPOR-RlpA) by mass spectrometry and structural analysis, which demonstrate that, in fact, the presence of peptide stems in the peptidoglycan abrogates binding. The crystal structures of the SPOR domain at atomic resolution (1.2 Å), in the apo state and in complex with different synthetic glycans, provide insight into the molecular basis for recognition and delineate a conserved pattern in other SPOR domains. The biological and structural observations presented here are followed up by molecular-dynamics simulations and by exploration of the effect on binding of distinct peptidoglycan modifications. These results provides an explanation to an unresolved question since decades: how the SPOR domains, present in almost all bacteria and with very little sequence homology, can all recognize the same type of cell-wall during bacterial division.

Martín Alcorlo, David A. Dik, Stefania De Benedetti, Kiran V. Mahasenan, Mijoon Lee, Teresa Domínguez-Gil, Dusan Hesek, Elena Lastochkin, Daniel López, Bill Boggess, Shahriar Mobashery* & Juan A. Hermoso*. Structural basis of denuded glycan recognition by SPOR domains in bacterial cell division. Nature Communications. (2019), 10, Article number: 5567