Negative regulation of MurZ and MurA underlies the essentiality of GpsB- and StkP-mediated protein phosphorylation in Streptococcus pneumoniae D39
© 2023 The Authors. Molecular Microbiology published by John Wiley & Sons Ltd..
GpsB links peptidoglycan synthases to other proteins that determine the shape of the respiratory pathogen Streptococcus pneumoniae (pneumococcus; Spn) and other low-GC Gram-positive bacteria. GpsB is also required for phosphorylation of proteins by the essential StkP(Spn) Ser/Thr protein kinase. Here we report three classes of frequently arising chromosomal duplications (≈21-176 genes) containing murZ (MurZ-family homolog of MurA) or murA that suppress ΔgpsB or ΔstkP. These duplications arose from three different repeated sequences and demonstrate the facility of pneumococcus to modulate gene dosage of numerous genes. Overproduction of MurZ or MurA alone or overproduction of MurZ caused by ΔkhpAB mutations suppressed ΔgpsB or ΔstkP phenotypes to varying extents. ΔgpsB and ΔstkP were also suppressed by MurZ amino-acid changes distant from the active site, including one in commonly studied laboratory strains, and by truncation or deletion of the homolog of IreB(ReoM). Unlike in other Gram-positive bacteria, MurZ is predominant to MurA in pneumococcal cells. However, ΔgpsB and ΔstkP were not suppressed by ΔclpCP, which did not alter MurZ or MurA amounts. These results support a model in which regulation of MurZ and MurA activity, likely by IreB(Spn), is the only essential requirement for StkP-mediated protein phosphorylation in exponentially growing D39 pneumococcal cells.
| Errataetall: | |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:120 |
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| Enthalten in: |
Molecular microbiology - 120(2023), 3 vom: 01. Sept., Seite 351-383 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Tsui, Ho-Ching Tiffany [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 25.09.2023 Date Revised 04.03.2024 published: Print-Electronic UpdateOf: bioRxiv. 2023 Mar 27;:. - PMID 37034771 Citation Status MEDLINE |
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| doi: |
10.1111/mmi.15122 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 100 | 1 | |a Tsui, Ho-Ching Tiffany |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Negative regulation of MurZ and MurA underlies the essentiality of GpsB- and StkP-mediated protein phosphorylation in Streptococcus pneumoniae D39 |
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| 500 | |a Date Revised 04.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a UpdateOf: bioRxiv. 2023 Mar 27;:. - PMID 37034771 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023 The Authors. Molecular Microbiology published by John Wiley & Sons Ltd. | ||
| 520 | |a GpsB links peptidoglycan synthases to other proteins that determine the shape of the respiratory pathogen Streptococcus pneumoniae (pneumococcus; Spn) and other low-GC Gram-positive bacteria. GpsB is also required for phosphorylation of proteins by the essential StkP(Spn) Ser/Thr protein kinase. Here we report three classes of frequently arising chromosomal duplications (≈21-176 genes) containing murZ (MurZ-family homolog of MurA) or murA that suppress ΔgpsB or ΔstkP. These duplications arose from three different repeated sequences and demonstrate the facility of pneumococcus to modulate gene dosage of numerous genes. Overproduction of MurZ or MurA alone or overproduction of MurZ caused by ΔkhpAB mutations suppressed ΔgpsB or ΔstkP phenotypes to varying extents. ΔgpsB and ΔstkP were also suppressed by MurZ amino-acid changes distant from the active site, including one in commonly studied laboratory strains, and by truncation or deletion of the homolog of IreB(ReoM). Unlike in other Gram-positive bacteria, MurZ is predominant to MurA in pneumococcal cells. However, ΔgpsB and ΔstkP were not suppressed by ΔclpCP, which did not alter MurZ or MurA amounts. These results support a model in which regulation of MurZ and MurA activity, likely by IreB(Spn), is the only essential requirement for StkP-mediated protein phosphorylation in exponentially growing D39 pneumococcal cells | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a GpsB peptidoglycan regulator | |
| 650 | 4 | |a KhpA/B RNA binding protein | |
| 650 | 4 | |a StkP protein kinase | |
| 650 | 4 | |a gene duplication and amplification | |
| 650 | 4 | |a peptidoglycan precursor synthesis | |
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| 700 | 1 | |a Joseph, Merrin |e verfasserin |4 aut | |
| 700 | 1 | |a Zheng, Jiaqi J |e verfasserin |4 aut | |
| 700 | 1 | |a Perez, Amilcar J |e verfasserin |4 aut | |
| 700 | 1 | |a Manzoor, Irfan |e verfasserin |4 aut | |
| 700 | 1 | |a Rued, Britta E |e verfasserin |4 aut | |
| 700 | 1 | |a Richardson, John D |e verfasserin |4 aut | |
| 700 | 1 | |a Branny, Pavel |e verfasserin |4 aut | |
| 700 | 1 | |a Doubravová, Linda |e verfasserin |4 aut | |
| 700 | 1 | |a Massidda, Orietta |e verfasserin |4 aut | |
| 700 | 1 | |a Winkler, Malcolm E |e verfasserin |4 aut | |
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