The Staphylococcus aureus cell division protein, DivIC, interacts with the cell wall and controls its biosynthesis

Abstract

Bacterial cell division is a complex, dynamic process that requires multiple protein components to orchestrate its progression. Many division proteins are highly conserved across bacterial species alluding to a common, basic mechanism. Central to division is a transmembrane trimeric complex involving DivIB, DivIC and FtsL in Gram-positives. Here, we show a distinct, essential role for DivIC in division and survival of Staphylococcus aureus. DivIC spatially regulates peptidoglycan synthesis, and consequently cell wall architecture, by influencing the recruitment to the division septum of the major peptidoglycan synthetases PBP2 and FtsW. Both the function of DivIC and its recruitment to the division site depend on its extracellular domain, which interacts with the cell wall via binding to wall teichoic acids. DivIC facilitates the spatial and temporal coordination of peptidoglycan synthesis with the developing architecture of the septum during cell division. A better understanding of the cell division mechanisms in S. aureus and other pathogenic microorganisms can provide possibilities for the development of new, more effective treatments for bacterial infections.

Autolysin-mediated peptidoglycan hydrolysis is required for the surface display of Staphylococcus aureus cell wall-anchored proteins

“…Cell fractionation preparation was performed as previously described ( 43 ), with minor modifications. Strains of interest were assessed in biological triplicate and grown overnight in 3 mL TSB for 18 h at 37 °C.…”

The cell cycle of Staphylococcus aureus: An updated review

“…MurJ is important for the recruitment of PG synthesis from the cell periphery to the septum due to the lipid II‐affinity of the PG biosynthesis proteins (Monteiro et al, 2018 ). DivIB and DivIC are cell wall‐binding proteins that also seem to have distinct functions at this checkpoint (Tinajero‐Trejo et al, 2022 ). Recently it was shown that DivIC has a role in recruiting the PG synthetases PBP2 and FtsW to the division septum, and interestingly, this was shown to depend on the binding of the extracellular domain of DivIC to WTA in the cell wall, suggesting that there may be chemical or architectural characteristics of the cell wall (PG and/or WTA) that is needed to allow further progression of septal synthesis (Tinajero‐Trejo et al, 2022 ).…”

“…DivIB and DivIC are cell wall‐binding proteins that also seem to have distinct functions at this checkpoint (Tinajero‐Trejo et al, 2022 ). Recently it was shown that DivIC has a role in recruiting the PG synthetases PBP2 and FtsW to the division septum, and interestingly, this was shown to depend on the binding of the extracellular domain of DivIC to WTA in the cell wall, suggesting that there may be chemical or architectural characteristics of the cell wall (PG and/or WTA) that is needed to allow further progression of septal synthesis (Tinajero‐Trejo et al, 2022 ). In addition, it was found that the arrival of MurJ to the septum corresponds to the time point during cytokinesis when the Z ring constriction rate increases (Figure 1d,e ).…”

Lipoteichoic acid biosynthesis byStaphylococcus aureusis controlled by the MspA protein through competitive interference

“…Therefore, the lengthening of this division stage likely drives the increase in cell size observed in the mutant, while in a small number of cases (Suppl. A lack of proteins involved in cell division or cell wall synthesis frequently causes an increase in cell size (Cheng, Missiakas and Schneewind, 2014;Do et al, 2020;Tinajero-Trejo et al, 2022;Wacnik et al, 2022). For example, deletion mutants of the genes encoding for UgtP or LtaA, proteins responsible for the lipoteichoic acid (LTA) glycolipid anchor synthesis and flipping (Gründling and Schneewind, 2007a) display longer LTA structures, enlargement of cell size, defects in septa formation and higher susceptibility to lytic enzymes (Hesser, Schaefer, et al, 2020).…”