yneA mRNA instability is involved in temporary inhibition of cell division during the SOS response of Bacillus megaterium

Buchholz, Meike; Nahrstedt, Hannes; Pillukat, Mike H.; Deppe, Veronika Maria; Meinhardt, Friedhelm

doi:10.1099/mic.0.064766-0

Cited by 9 publications

(10 citation statements)

References 48 publications

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“…In this organism, we and others have previously identified lexA and noted an open reading frame (designated sosA) that is divergently transcribed from lexA and controlled by the LexA repressor and the SOS response (Anderson et al, 2006;Cirz et al, 2007;Mesak et al, 2008;Cohn et al, 2011). The location of sosA adjacent to lexA indicated that it might encode a cell division inhibitor, as similar gene synteny has been observed for SOS-induced cell division inhibitors encoded by Gram-positive, rod-shaped bacteria, namely Bacillus subtilis (Kawai et al, 2003), Bacillus megaterium (Buchholz et al, 2013), Listeria monocytogenes (van der Veen et al, 2007;, Mycobacterium tuberculosis (Chauhan et al, 2006) and Corynebacterium glutamicum (Ogino et al, 2008) (Fig. 1A).…”

Section: Introductionsupporting

confidence: 55%

“…Similarly, YneA from B. subtilis was originally reported to be regulated by proteolysis, although by an undefined mechanism, and a point mutation at its extreme C‐terminus generated a stabilized yet functional variant of the cell division inhibitor (Mo and Burkholder, ). In B. megaterium , the temporal expression of a YneA homologue has been suggested to be due to mRNA instability (Buchholz et al , ). We demonstrate that a minor truncation of the C‐terminus of SosA increases cell division inhibitory activity (Fig.…”

Section: Discussionmentioning

confidence: 99%

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SosA inhibits cell division in Staphylococcus aureus in response to DNA damage

Bojer

Wacnik

Kjelgaard

et al. 2019

Molecular Microbiology

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Summary Inhibition of cell division is critical for viability under DNA‐damaging conditions. DNA damage induces the SOS response that in bacteria inhibits cell division while repairs are being made. In coccoids, such as the human pathogen, Staphylococcus aureus, this process remains poorly studied. Here, we identify SosA as the staphylococcal SOS‐induced cell division inhibitor. Overproduction of SosA inhibits cell division, while sosA inactivation sensitizes cells to genotoxic stress. SosA is a small, predicted membrane protein with an extracellular C‐terminal domain in which point mutation of residues that are conserved in staphylococci and major truncations abolished the inhibitory activity. In contrast, a minor truncation led to SosA accumulation and a strong cell division inhibitory activity, phenotypically similar to expression of wild‐type SosA in a CtpA membrane protease mutant. This suggests that the extracellular C‐terminus of SosA is required both for cell division inhibition and for turnover of the protein. Microscopy analysis revealed that SosA halts cell division and synchronizes the cell population at a point where division proteins such as FtsZ and EzrA are localized at midcell, and the septum formation is initiated but unable to progress to closure. Thus, our findings show that SosA is central in cell division regulation in staphylococci.

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Section: Introductionsupporting

confidence: 55%

Section: Discussionmentioning

confidence: 99%

SosA inhibits cell division in Staphylococcus aureus in response to DNA damage

Bojer

Wacnik

Kjelgaard

et al. 2019

Molecular Microbiology

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“…Similarly, an as-yet-unidentified component of the B. subtilis late divisome serves as a target for SOS-induced YneA 131 . SulA acts transiently because it is proteolytically unstable, whereas instability of yneA mRNA ensures transient activity of its gene product 132 . Oxygen and heat stress also modulate FtsZ assembly.…”

Section: Metabolic and Stress Inputsmentioning

confidence: 99%

Splitsville: structural and functional insights into the dynamic bacterial Z ring

Haeusser

Margolin²

2016

Nat Rev Microbiol

299

283

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Preface Bacteria must divide in order to increase in number and colonize their niche. Binary fission is the most widespread means of bacterial cell division, but even this relatively simple mechanism displays many variations on a theme. In most bacteria, the tubulin homolog FtsZ assembles into a ring structure (Z ring) at the site of cytokinesis and recruits additional proteins to form a large protein machine (divisome) that spans the membrane. Here we discuss current insights into the regulation of Z ring assembly and how the divisome drives membrane invagination and septal cell wall growth while still flexibly responding to various cellular inputs.

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“…subtilis was reported to be regulated by proteolysis (36), while in B. megaterium, the temporal expression of a YneA homologue has been suggested to be due to mRNA instability (25). We demonstrated that a minor truncation of the C-terminus of SosA yields a hyper-potent cell-division inhibitor (Fig.…”

Section: Endogenous Cell-division Inhibition Must Be Stringently Regumentioning

confidence: 63%

“…and noted an open reading frame (designated sosA) that is divergently transcribed from lexA and is controlled by the LexA repressor and the SOS response (20)(21)(22)(23). The location of sosA adjacent to lexA indicated that it might encode a cell division inhibitor as similar gene synteny has been observed for cell division inhibitors encoded by Gram-positive, rod shaped bacteria namely Bacillus subtilis (24), Bacillus megaterium (25), Listeria monocytogenes (26,27), Mycobacterium tuberculosis (28) and Corynebacterium glutamicum (29) (Fig. 1A).…”

Section: Introductionmentioning

confidence: 81%

SosA inhibits cell division inStaphylococcus aureusin response to DNA damage

Bojer

Wacnik

Kjelgaard

et al. 2018

Preprint

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Inhibition of cell division is critical for cell viability under DNA damaging conditions. In bacterial cells, DNA damage induces the SOS response, a process that inhibits cell division while repairs are being made. In coccoid bacteria, such as the human pathogen Staphylococcus aureus, the process remains poorly understood. Here we have characterized an SOS-induced cell-division inhibitor, SosA, in S. aureus. We find that in contrast to the wildtype, sosA mutant cells continue division under DNA damaging conditions with decreased viability as a consequence. Conversely, overproduction of SosA leads to cell division inhibition and reduced growth. The SosA protein is localized in the bacterial membrane and mutation of an extracellular amino acid, conserved between homologs of other staphylococcal species, abolished the inhibitory activity as did truncation of the C-terminal 30 amino acids. In contrast, C-terminal truncation of 10 amino acids lead to SosA accumulation and a strong cell division inhibitory activity. A similar phenotype was observed upon expression of wildtype SosA in a mutant lacking the membrane protease, CtpA. Thus, the extracellular C-terminus of SosA is required both for cell-division inhibition and for turnover of the protein. Functional studies showed that SosA is likely to interact with one or more divisome components and, without interfering with early cell-division events, halts cell division at a point where septum formation is initiated yet being unable to progress to septum closure. Our findings provide important insights into cell-division regulation in staphylococci that may foster development of new classes of antibiotics targeting this essential process.ImportanceStaphylococcus aureus is a serious human pathogen and a model organism for cell-division studies in spherical bacteria. We show that SosA is the DNA-damage-inducible cell-division inhibitor in S. aureus that upon expression causes cell swelling and cessation of the cell cycle at a characteristic stage post septum initiation but prior to division plate completion. SosA appears to function via an extracellular activity and is likely to do so by interfering with the essential membrane-associated division proteins, while at the same time being negatively regulated by the membrane protease CtpA. This report represents the first description of the process behind cell-division inhibition in coccoid bacteria. As several pathogens are included in this category, uncovering the molecular details of SosA activity and control can lead to identification of new targets for development of valuable anti-bacterial drugs.

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yneA mRNA instability is involved in temporary inhibition of cell division during the SOS response of Bacillus megaterium

Cited by 9 publications

References 48 publications

SosA inhibits cell division in Staphylococcus aureus in response to DNA damage

SosA inhibits cell division in Staphylococcus aureus in response to DNA damage

Splitsville: structural and functional insights into the dynamic bacterial Z ring

SosA inhibits cell division inStaphylococcus aureusin response to DNA damage

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