The roles of GpsB and DivIVA in Staphylococcus aureus growth and division

Sutton, Joshua A. F.; Cooke, Mark; Tinajero-Trejo, Mariana; Wacnik, Katarzyna; Salamaga, Bartłomiej; Portman-Ross, Callum; Lund, Victoria A.; Hobbs, Jamie K.; Foster, Simon J.

doi:10.3389/fmicb.2023.1241249

Cited by 8 publications

(8 citation statements)

References 80 publications

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“…We, therefore, focused on understanding the mechanism by which GpsB regulates cell shape in S. aureus . Interestingly, data concurrent with ours show that gpsB deletion in S. aureus SH1000 also results in more spherical cells ( 47 ).…”

Section: Discussionsupporting

confidence: 85%

“…GpsB is a small coiled-coil protein, which localizes at midcell, previously reported to be essential in S. aureus strain SH1000 ( 44 ). However, a transposon mutant in gpsB is present in the NTML ( 17 ) and in additional reported transposon screenings ( 45 ), and deletion mutants of gpsB have been recently reported ( 46 ) including in SH1000 ( 47 ). We could also easily delete gpsB from both COL and JE2 strains, indicating that gpsB is dispensable for growth in various S. aureus strains.…”

Section: Resultsmentioning

confidence: 99%

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The role of GpsB in Staphylococcus aureus cell morphogenesis

Costa,

Saraiva,

Veiga

et al. 2024

mBio

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Staphylococcus aureus is a Gram-positive clinical pathogen, which is currently the second cause of death by antibiotic-resistant infections worldwide. For decades, S. aureus cells were thought to be spherical and lack the ability to undergo elongation. However, super-resolution microscopy techniques allowed us to observe the minor morphological changes that occur during the cell cycle of this pathogen, including cell elongation. S. aureus elongation is not required for normal growth in laboratory conditions. However, it seems to be essential in the context of some infections, such as osteomyelitis, during which S. aureus cells apparently elongate to invade small channels in the bones. In this work, we uncovered new determinants required for S. aureus cell elongation. In particular, we show that GpsB has an important role in the spatio-temporal regulation of PBP2 and PBP4, two proteins involved in peptidoglycan synthesis, contributing to the maintenance of the correct cell morphology in S. aureus .

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Section: Discussionsupporting

confidence: 85%

Section: Resultsmentioning

confidence: 99%

The role of GpsB in Staphylococcus aureus cell morphogenesis

Costa,

Saraiva,

Veiga

et al. 2024

mBio

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“…While GpsB is dispensable, or conditionally essential in most Firmicutes ( Rismondo et al, 2016 ; Fleurie et al, 2014 ; Claessen et al, 2008 ; Tavares et al, 2008 ), it was reported to be essential for growth in Staphylococcus aureus ( Santiago et al, 2015 ; Gillaspy, 2006 ). However, recent studies indicate that gpsB may not be essential, but nevertheless plays a significant role in maintaining S. aureus cell morphology ( Sutton et al, 2023 ; Bartlett et al, 2023 ; Costa et al, 2023 ). In particular, the importance of S. aureus GpsB ( Sa GpsB) for cell division is underscored by its unique ability to regulate FtsZ polymerization in S. aureus ( Eswara et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Staphylococcus aureus FtsZ and PBP4 bind to the conformationally dynamic N-terminal domain of GpsB

Sacco,

Hammond,

Noor

et al. 2024

eLife

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In the Firmicutes phylum, GpsB is a membrane associated protein that coordinates peptidoglycan synthesis with cell growth and division. Although GpsB has been studied in several bacteria, the structure, function, and interactome of Staphylococcus aureus GpsB is largely uncharacterized. To address this knowledge gap, we solved the crystal structure of the N-terminal domain of S. aureus GpsB, which adopts an atypical, asymmetric dimer, and demonstrates major conformational flexibility that can be mapped to a hinge region formed by a three-residue insertion exclusive to Staphylococci. When this three-residue insertion is excised, its thermal stability increases, and the mutant no longer produces a previously reported lethal phenotype when overexpressed in Bacillus subtilis. In S. aureus, we show that these hinge mutants are less functional and speculate that the conformational flexibility imparted by the hinge region may serve as a dynamic switch to finetune the function of the GpsB complex and/or to promote interaction with its various partners. Furthermore, we provide the first biochemical, biophysical, and crystallographic evidence that the N-terminal domain of GpsB binds not only PBP4, but also FtsZ, through a conserved recognition motif located on their C-termini, thus coupling peptidoglycan synthesis to cell division. Taken together, the unique structure of S. aureus GpsB and its direct interaction with FtsZ/PBP4 provide deeper insight into the central role of GpsB in S. aureus cell division.

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“…Several studies have shown that DivIVA localizes at the division site in various bacterial species and in some cases at the cell poles, including in S. pneumoniae (Cramer et al, 2024; Fadda et al, 2007; Fleurie et al, 2014; Sutton et al, 2023). To further document the localization and dynamics of the pneumococcal DivIVA, we constructed a functional DivIVA-HT fusion at the endogenous divIVA locus (Fig.…”

Section: Resultsmentioning

confidence: 99%

DivIVA controls the dynamics of septum splitting and cell elongation inStreptococcus pneumoniae

Trouve,

Zapun,

Bellard

et al. 2024

Preprint

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Bacterial shape and division rely on the dynamics of cell wall assembly, which involves regulated synthesis and cleavage of the peptidoglycan. In ovococci, these processes are coordinated in an annular mid-cell region with nanometric dimensions. More precisely, the cross-wall that is synthesized by the divisome is split to generate lateral wall, whose expansion is insured by insertion of so-called peripheral peptidoglycan by the elongasome. Septum cleavage and peripheral peptidoglycan synthesis are thus crucial remodeling events for ovococcal cell division and elongation. The structural DivIVA protein has long been known as a major regulator of these processes but its mode of action remains unknown. Here, we integrate click chemistry-based peptidoglycan labeling, direct stochastic optical reconstruction microscopy and in silico modeling, as well as epifluorescence and stimulated emission depletion microscopy to investigate the role of DivIVA inStreptococcus pneumoniaecell morphogenesis. Our work reveals two distinct phases of peptidoglycan remodeling along the cell cycle, that are differentially controlled by DivIVA. In particular, we show that DivIVA ensures homogeneous septum cleavage and peripheral peptidoglycan synthesis around the division site, and their maintenance throughout the cell cycle. Our data additionally suggest that DivIVA impacts the contribution of the elongasome and class A PBPs to cell elongation. We also report the position of DivIVA on either side of the septum, consistent with its known affinity for negatively curved membranes. Finally, we take the opportunity provided by these new observations to propose hypotheses for the mechanism of action of this key morphogenetic protein.

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The roles of GpsB and DivIVA in Staphylococcus aureus growth and division

Cited by 8 publications

References 80 publications

The role of GpsB in Staphylococcus aureus cell morphogenesis

The role of GpsB in Staphylococcus aureus cell morphogenesis

Staphylococcus aureus FtsZ and PBP4 bind to the conformationally dynamic N-terminal domain of GpsB

DivIVA controls the dynamics of septum splitting and cell elongation inStreptococcus pneumoniae

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