GpsB is an accessory Z-ring anchor
Authors: Bhattacharya Dipanwita , McKnight Lily , King Asher , Eswara Prahathees J. 
Published: May 2024

AbstractBacterial cytokinesis is a well-coordinated process in which multiple proteins, collectively called the divisome, are recruited to the site of division. A key member of the divisome is FtsZ which forms a ring-like structure (Z-ring) to mark the division site through its association with Z-ring anchors. Synchronized movement of Z-ring filaments and peptidoglycan synthesis along the axis of division help generate a division septum to separate the daughter cells. Thus, FtsZ needs to be linked to the PG synthesis machinery. GpsB is a highly conserved protein among the members of the Firmicutes phylum which has been shown to regulate cell wall synthesis through interaction with penicillin binding proteins. Previously published data from our lab established GpsB as a member of the divisome which directly interacts with FtsZ inStaphylococcus aureus. More specifically, we showed that GpsB binds to FtsZ by recognizing the R-X-X-R sequence in its C- terminal tail (CTT) region. As the GpsB recognition sequence is also present inBacillus subtilis, we speculated that GpsB-FtsZ interaction might occur in this organism as well. In support of our prediction, previous studies reported that disruption ofgpsBandezrAorgpsBandftsAis deleterious. Given that both EzrA and FtsA are known Z-ring anchors, we hypothesized that in the absence of other FtsZ anchors, GpsB can fulfill this role inB. subtilis. Our data, taken together, conclusively shows that GpsB is a Z-ring anchor inB. subtilisand this role of GpsB only becomes apparent in the absence of other FtsZ anchoring proteins. Based on the conserved nature of the R-X-X-R sequence in FtsZ- CTT, we also tested GpsB-FtsZ interaction inEnterococcus faecalisandListeria monocytogenesand show that this recognition motif dependent interaction is present in the former but not the latter. Our results suggest the possibility of C-terminal R-X-X-R independent interaction inL. monocytogenesandStreptococcus pneumoniae. Thus, it appears that GpsB may serve as an accessory Z-ring anchor in multiple organisms.ImportanceCell division is essential for production of offsprings and propagation of life. In bacteria, a key tubulin-like cell division protein FtsZ is brought to the division site by the action of multiple regulators. Arrival of FtsZ and activation of cell wall synthesis are needed to build a division septum to separate the daughter cells. As such, this vital process is controlled by redundant fail-safe mechanisms. For instance, multiple proteins can anchor FtsZ to the membrane at the division site. In this report, we reveal that yet another protein, GpsB, could serve as a back-up FtsZ anchor. GpsB is normally associated with cell wall synthesis in most organisms of the Firmicutes phylum. However, in the absence of other known dedicated FtsZ anchoring factors, GpsB is able to step in to rescue cell division. We provide evidence that this GpsB-FtsZ interaction is present inStaphylococcus aureus,Bacillus subtilis,Enterococcus faecalis,Listeria monocytogenes, and possiblyStreptococcus pneumoniae. As the rapid rise in antibiotic resistance is threatening public health globally, knowledge of unique important cell division factors could be harnessed to develop new antibacterial therapeutics.