The cell cycle of <i>Staphylococcus aureus</i>: An updated review

Barbuti, Maria D.; Myrbråten, Ine Storaker; Angeles, Danae Morales; Kjos, Morten

doi:10.1002/mbo3.1338

Cited by 18 publications

(15 citation statements)

References 155 publications

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“…We observed optimal staining of the S. aureus cell wall in these samples at slightly higher concentrations (130 nM), probably because of low-level adsorption to the tissue. Whereas anti-SA stained only the outer surface proteins of S. aureus , Van-JF 669 stained also the septum between two emerging daughter cells, which is an area of the cell wall with particularly active de novo peptidoglycan synthesis (Figure A–C) . These data confirm the identity of Van-JF 669 -positive particles as S. aureus .…”

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confidence: 69%

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A Far-Red Fluorescent Probe to Visualize Gram-Positive Bacteria in Patient Samples

Jantarug,

Tripathi,

Morin

et al. 2024

ACS Infect. Dis.

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Gram-positive bacteria, in particular Staphylococcus aureus (S. aureus), are the leading bacterial cause of death in highincome countries and can cause invasive infections at various body sites. These infections are associated with prolonged hospital stays, a large economic burden, considerable treatment failure, and high mortality rates. So far, there is only limited knowledge about the specific locations where S. aureus resides in the human body during various infections. Hence, the visualization of S. aureus holds significant importance in microbiological research. Herein, we report the development and validation of a far-red fluorescent probe to detect Gram-positive bacteria, with a focus on staphylococci, in human biopsies from deep-seated infections. This probe displays strong fluorescence and low background in human tissues, outperforming current tools for S. aureus detection. Several applications are demonstrated, including fixed-and live-cell imaging, flow cytometry, and super-resolution bacterial imaging.

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supporting

confidence: 69%

“…Whereas anti-SA stained only the outer surface proteins of S. aureus , Van-JF 669 stained also the septum between two emerging daughter cells, which is an area of the cell wall with particularly active de novo peptidoglycan synthesis ( Figure 3 A–C). 22 These data confirm the identity of Van-JF 669 -positive particles as S. aureus .…”

supporting

confidence: 61%

A Far-Red Fluorescent Probe to Visualize Gram-Positive Bacteria in Patient Samples

Jantarug,

Tripathi,

Morin

et al. 2024

ACS Infect. Dis.

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“…In addition to its role in teichoic acid biosynthesis, we found that WalKR controls essential genes involved in the initiation of DNA replication. In S. aureus , DNA replication is initiated by binding of DnaA to AT-rich regions at the origin of replication, oriC 63 . This process is tightly controlled, as mistiming of initiation results in aberrant cell division 64 .…”

Section: Discussionmentioning

confidence: 99%

The two-component regulator WalKR provides an essential link between cell wall homeostasis with DNA replication inStaphylococcus aureus

Sharkey

Guérillot

Walsh

et al. 2023

Preprint

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Among the 16 two-component systems (TCSs) in the opportunistic human pathogen Staphylococcus aureus, only WalKR is essential. Like orthologous systems in other Bacillota, S. aureus WalKR controls autolysins involved in peptidoglycan remodelling and is therefore intimately involved in cell division. However, despite the importance of WalKR in S. aureus, the basis for its essentiality is not understood and the regulon poorly defined. Here, we use a panel of isogenic walKR mutants with a spectrum of activity, combined with functional genomics including ChIP-seq to identify a consensus WalR DNA-binding motif and define the direct WalKR regulon. As previously shown, the direct regulon includes multiple autolysin genes. However, we also show WalR directly regulates at least five essential genes involved in (i) lipoteichoic acid synthesis (ltaS), (ii) translation (rplK), (iii) DNA compaction (hup), (iv) initiation of DNA replication (dnaA, hup) and (v) purine nucleotide metabolism (prs). Thus, WalKR in S. aureus is a polyfunctional regulator with fundamental control over critical cell systems, linking cell wall homeostasis with purine biosynthesis, protein biosynthesis, and DNA replication. Our findings explain the essentiality of this locus and should reignite interest in WalKR as a bona fide target for novel anti-staphylococcal therapeutics.

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“…LtaS has also been demonstrated to mainly accumulate at the septum in S. aureus , indicating that LTA synthesis predominantly occurs at the division site (19). Together this suggest that LTA biosynthesis is tightly coordinated with peptidoglycan synthesis and other processes during the staphylococcal cell cycle (20).…”

Section: Introductionmentioning

confidence: 97%

The function of CozE proteins is linked to lipoteichoic acid biosynthesis inStaphylococcus aureus

Barbuti,

Lambert,

Myrbråten

et al. 2023

Preprint

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To maintain cell integrity and facilitate cell division inStaphylococcus aureus, a well-coordinated interplay between membrane biogenesis, peptidoglycan formation, and teichoic acid synthesis is crucial. However, the molecular mechanisms and regulatory pathways that underpin their coordination are still poorly understood. CozE constitute a conserved family of membrane proteins implicated in cell division via regulation of penicillin binding proteins. It has been shown that the two staphylococcalcozEgenes (cozEaandcozEb) constitute a synthetic lethal gene pair. Depletion of CozEa and CozEb simultaneously inS. aureusresulted in severely defective cell division phenotypes, reminiscent of cell lacking lipoteichoic acid (LTA). Indeed, we demonstrate that there is an intricate interplay between CozE, biosynthesis of LTA, and membrane homeostasis inS. aureus. By screening for potential genetic links, we establish that there is synthetic lethal relationship between CozE and UgtP, the enzyme synthesizing the LTA glycolipid anchor Glc2DAG. On the contrary, in cells lacking LtaA, the flippase of Glc2DAG, the essentiality of CozEa and CozEb was alleviated. Furthermore, by immunoblotting, we found that CozEb plays a unique role in controlling LTA polymer length and stability. Using reconstituted proteoliposomes, we also demonstrated that CozE proteins modulate the glycolipid flipping activity of LtaAin vitro. Together, the results demonstrate a new function of CozE proteins, facilitating proper membrane homeostasis and LTA biosynthesis inS. aureus.

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The cell cycle of Staphylococcus aureus: An updated review

Cited by 18 publications

References 155 publications

A Far-Red Fluorescent Probe to Visualize Gram-Positive Bacteria in Patient Samples

A Far-Red Fluorescent Probe to Visualize Gram-Positive Bacteria in Patient Samples

The two-component regulator WalKR provides an essential link between cell wall homeostasis with DNA replication inStaphylococcus aureus

The function of CozE proteins is linked to lipoteichoic acid biosynthesis inStaphylococcus aureus

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