The Elongation of Ovococci

Philippe, Jules; Vernet, Thierry; Zapun, André

doi:10.1089/mdr.2014.0032

Cited by 33 publications

(53 citation statements)

References 40 publications

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“…Second, inactivation or depletion of proteins that function late in cell division (e.g., for septum remodeling or closure) are associated with a variety of phenotypes but not cell lysis (39,40,47,60,62,64), whereas those involved in peripheral or septal PG synthesis result in cell lysis, independently of the respective protein's role in cell elongation or cell division (40, 41, 44, 65, 66). This correlation underscores the intimate coordination and chronology between the two PG biosynthetic machineries (34)(35)(36)43). This connection is best illustrated by S. pneumoniae PBP2x (the E. coli PBP3 homolog), which is the essential transpeptidase required to build the cell division septum.…”

Section: Discussionmentioning

confidence: 70%

“…However, genetic evidence for the essential role of the Fts proteins involved in the initial steps of cell division is presently lacking. In particular, it is not yet known how the PG synthetic complex involved in septation (the divisome) is assembled and coordinated with the protein complex involved in peripheral elongation (the elongasome) (7,42), which in S. pneumoniae is also located at midcell (35,36,(43)(44)(45).…”

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Roles of the Essential Protein FtsA in Cell Growth and Division in Streptococcus pneumoniae

et al. 2017

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Streptococcus pneumoniae is an ovoid-shaped Gram-positive bacterium that grows by carrying out peripheral and septal peptidoglycan (PG) synthesis, analogous to model bacilli, such as Escherichia coli and Bacillus subtilis. In the model bacilli, FtsZ and FtsA proteins assemble into a ring at midcell and are dedicated to septal PG synthesis but not peripheral PG synthesis; hence, inactivation of FtsZ or FtsA results in long filamentous cells unable to divide. Here, we demonstrate that FtsA and FtsZ colocalize at midcell in S. pneumoniae and that partial depletion of FtsA perturbs septum synthesis, resulting in elongated cells with multiple FtsZ rings that fail to complete septation. Unexpectedly, complete depletion of FtsA resulted in the delocalization of FtsZ rings and ultimately cell ballooning and lysis. In contrast, depletion or deletion of gpsB and sepF, which in B. subtilis are synthetically lethal with ftsA, resulted in enlarged and elongated cells with multiple FtsZ rings, with deletion of sepF mimicking partial depletion of FtsA. Notably, cell ballooning was not observed, consistent with later recruitment of these proteins to midcell after Z-ring assembly. The overproduction of FtsA stimulates septation and suppresses the cell division defects caused by the deletion of sepF and gpsB under some conditions, supporting the notion that FtsA shares overlapping functions with GpsB and SepF at later steps in the division process. Our results indicate that, in S. pneumoniae, both GpsB and SepF are involved in septal PG synthesis, whereas FtsA and FtsZ coordinate both peripheral and septal PG synthesis and are codependent for localization at midcell.IMPORTANCE Streptococcus pneumoniae (pneumococcus) is a clinically important human pathogen for which more therapies against unexploited essential targets, like cell growth and division proteins, are needed. Pneumococcus is an ovoid-shaped Gram-positive bacterium with cell growth and division properties that have important distinctions from those of rod-shaped bacteria. Gaining insights into these processes can thus provide valuable information to develop novel antimicrobials. Whereas rods use distinctly localized protein machines at different cellular locations to synthesize peripheral and septal peptidoglycans, we present evidence that S. pneumoniae organizes these two machines at a single location in the middle of dividing cells. Here, we focus on the properties of the actin-like protein FtsA as an essential orchestrator of peripheral and septal growth in this bacterium.KEYWORDS FtsA, Gram-positive cocci, Streptococcus pneumoniae, cell division

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Section: Discussionmentioning

confidence: 70%

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Roles of the Essential Protein FtsA in Cell Growth and Division in Streptococcus pneumoniae

et al. 2017

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“…In wild‐type cells, the primary pathway for peripheral PG synthesis is initiated when the TG activity of PBP1a builds a new glycan strand from external Lipid II precursors. The genetic relationships in this article are not easily reconciled with RodA acting exclusively as a peripheral‐PG Lipid II flippase; instead, they suggest that RodA is additionally necessary for PBP2b TP function, possibly by direct interaction, as suggested by biochemical studies (Philippe et al ., ). Functional interaction between RodA and PBP2b is suggested by the observations that Δ pbp1a mutations do not suppress Δ pbp2b or Δ rodA mutations, but suppress Δ mltG , Δ mreCD or Δ rodZ mutations (Fig.…”

Section: Discussionmentioning

confidence: 97%

“…Depletion of these regulatory proteins results in elongation or increased sphericity of cells, consistent with roles in septal or peripheral PG synthesis, respectively (Land and Winkler, ; Tsui et al ., ). Corroborated interactions have been demonstrated with some regulatory proteins [e.g., PBP2x and the StkP protein kinase (Morlot et al ., ) and PBP2b and RodA (Philippe et al ., )], but for the most part, the composition, chronology and coordination between the septal and peripheral PG synthesis machines remains speculative (Massidda et al ., ; Philippe et al ., ; Gisch et al ., ). The current model of the peripheral PG synthesis machine (Supporting Information Fig.…”

Section: Introductionmentioning

confidence: 99%

Suppression of a deletion mutation in the gene encoding essential PBP2b reveals a new lytic transglycosylase involved in peripheral peptidoglycan synthesis in Streptococcus pneumoniae D39

Tsui

Zheng

Magallon

et al. 2016

Molecular Microbiology

269

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SUMMARY In ellipsoid-shaped ovococcus bacteria, such as the pathogen Streptococcus pneumoniae (pneumococcus), side-wall (peripheral) peptidoglycan (PG) synthesis emanates from midcells and is catalyzed by the essential class B penicillin-binding protein PBP2b transpeptidase (TP). We report that mutations that inactivate the pneumococcal YceG-domain protein, Spd_1346 (renamed MltG), remove the requirement for PBP2b. ΔmltG mutants in unencapsulated strains accumulate inactivation mutations of class A PBP1a, which possesses TP and transglycosylase (TG) activities. The “synthetic viable” genetic relationship between Δpbp1a and ΔmltG mutations extends to essential ΔmreCD and ΔrodZ mutations that misregulate peripheral PG synthesis. Remarkably, the single MltG(Y488D) change suppresses the requirement for PBP2b, MreCD, RodZ, and RodA. Structural modeling and comparisons, catalytic-site changes, and an interspecies chimera indicate that pneumococcal MltG is the functional homologue of the recently reported MltG endo-lytic transglycosylase of Escherichia coli. Depletion of pneumococcal MltG or mltG(Y488D) increases sphericity of cells, and MltG localizes with peripheral PG synthesis proteins during division. Finally, growth of Δpbp1a ΔmltG or mltG(Y488D) mutants depends on induction of expression of the WalRK TCS regulon of PG hydrolases. These results fit a model in which MltG releases anchored PG glycan strands synthesized by PBP1a for crosslinking by a PBP2b:RodA complex in peripheral PG synthesis.

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“…Finetuning the dynamics of peptidoglycan assembly is essential for proper cell division and shape determination. In ovoid bacteria, the synthesis of peptidoglycan is thought to involve two machineries that allow bacteria to elongate and divide (6,7). A set of six penicillin-binding proteins (PBPs) catalyzes the last step of peptidoglycan assembly in S. pneumoniae.…”

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Mechanism of β-Lactam Action in Streptococcus pneumoniae: the Piperacillin Paradox

Philippe

Gallet

Morlot

et al. 2015

Antimicrob Agents Chemother

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fThe human pathogen Streptococcus pneumoniae has been treated for decades with ␤-lactam antibiotics. Its resistance is now widespread, mediated by the expression of mosaic variants of the target enzymes, the penicillin-binding proteins (PBPs). Understanding the mode of action of ␤-lactams, not only in molecular detail but also in their physiological consequences, will be crucial to improving these drugs and any counterresistances. In this work, we investigate the piperacillin paradox, by which this ␤-lactam selects primarily variants of PBP2b, whereas its most reactive target is PBP2x. These PBPs are both essential monofunctional transpeptidases involved in peptidoglycan assembly. PBP2x participates in septal synthesis, while PBP2b functions in peripheral elongation. The formation of the "lemon"-shaped cells induced by piperacillin treatment is consistent with the inhibition of PBP2x. Following the examination of treated and untreated cells by electron microscopy, the localization of the PBPs by epifluorescence microscopy, and the determination of the inhibition time course of the different PBPs, we propose a model of peptidoglycan assembly that accounts for the piperacillin paradox.

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The Elongation of Ovococci

Cited by 33 publications

References 40 publications

Roles of the Essential Protein FtsA in Cell Growth and Division in Streptococcus pneumoniae

Roles of the Essential Protein FtsA in Cell Growth and Division in Streptococcus pneumoniae

Suppression of a deletion mutation in the gene encoding essential PBP2b reveals a new lytic transglycosylase involved in peripheral peptidoglycan synthesis in Streptococcus pneumoniae D39

Mechanism of β-Lactam Action in Streptococcus pneumoniae: the Piperacillin Paradox

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