SmdA is a Novel Cell Morphology Determinant in Staphylococcus aureus
ABSTRACT Cell division and cell wall synthesis in staphylococci need to be precisely coordinated and controlled to allow the cell to multiply while maintaining its nearly spherical shape. The mechanisms ensuring correct placement of the division plane and synthesis of new cell wall have been studied...
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2022-04-01
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| Series: | mBio |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mbio.03404-21 |
| _version_ | 1818115851790843904 |
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| author | Ine Storaker Myrbråten Gro Anita Stamsås Helena Chan Danae Morales Angeles Tiril Mathiesen Knutsen Zhian Salehian Volha Shapaval Daniel Straume Morten Kjos |
| author_facet | Ine Storaker Myrbråten Gro Anita Stamsås Helena Chan Danae Morales Angeles Tiril Mathiesen Knutsen Zhian Salehian Volha Shapaval Daniel Straume Morten Kjos |
| author_sort | Ine Storaker Myrbråten |
| collection | DOAJ |
| description | ABSTRACT Cell division and cell wall synthesis in staphylococci need to be precisely coordinated and controlled to allow the cell to multiply while maintaining its nearly spherical shape. The mechanisms ensuring correct placement of the division plane and synthesis of new cell wall have been studied intensively. However, hitherto unknown factors and proteins are likely to play key roles in this complex interplay. Here, we identified and investigated a protein with a major influence on cell morphology in Staphylococcus aureus. The protein, named SmdA (for staphylococcal morphology determinant A), is a membrane protein with septum-enriched localization. By CRISPRi knockdown and overexpression combined with different microscopy techniques, we demonstrated that proper levels of SmdA were necessary for cell division, including septum formation and cell splitting. We also identified conserved residues in SmdA that were critical for its functionality. Pulldown and bacterial two-hybrid interaction experiments showed that SmdA interacted with several known cell division and cell wall synthesis proteins, including penicillin-binding proteins (PBPs) and EzrA. Notably, SmdA also affected susceptibility to cell wall targeting antibiotics, particularly in methicillin-resistant S. aureus (MRSA). Together, our results showed that S. aureus was dependent on balanced amounts of membrane attached SmdA to carry out proper cell division. IMPORTANCE Staphylococcus aureus is an important human and animal pathogen. Antibiotic resistance is a major problem in the treatment of staphylococcal infections, and cell division and cell wall synthesis factors have previously been shown to modulate susceptibility to antibiotics in this species. Here, we investigated the function of a protein named SmdA, which was identified based on its septal localization and knockdown phenotype resulting in defective cellular morphologies. We demonstrated that this protein was critical for normal cell division in S. aureus. Depletion of SmdA sensitized resistant staphylococci to β-lactam antibiotics. This work revealed a new staphylococcal cell division factor and a potential future target for narrow-spectrum antimicrobials or compounds to resensitize antibiotic-resistant staphylococcal strains. |
| first_indexed | 2024-12-11T04:13:12Z |
| format | Article |
| id | doaj.art-2dc7f34423ac42c8b81a061254a52612 |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-12-11T04:13:12Z |
| publishDate | 2022-04-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-2dc7f34423ac42c8b81a061254a526122022-12-22T01:21:18ZengAmerican Society for MicrobiologymBio2150-75112022-04-0113210.1128/mbio.03404-21SmdA is a Novel Cell Morphology Determinant in Staphylococcus aureusIne Storaker Myrbråten0Gro Anita Stamsås1Helena Chan2Danae Morales Angeles3Tiril Mathiesen Knutsen4Zhian Salehian5Volha Shapaval6Daniel Straume7Morten Kjos8Faculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, Ås, NorwayFaculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, Ås, NorwayStructural Cellular Biology Unit, Okinawa Institute of Science and Technology, Okinawa, JapanFaculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, Ås, NorwayFaculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, Ås, NorwayFaculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, Ås, NorwayFaculty of Science and Technology, Norwegian University of Life Sciences, Ås, NorwayFaculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, Ås, NorwayFaculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, Ås, NorwayABSTRACT Cell division and cell wall synthesis in staphylococci need to be precisely coordinated and controlled to allow the cell to multiply while maintaining its nearly spherical shape. The mechanisms ensuring correct placement of the division plane and synthesis of new cell wall have been studied intensively. However, hitherto unknown factors and proteins are likely to play key roles in this complex interplay. Here, we identified and investigated a protein with a major influence on cell morphology in Staphylococcus aureus. The protein, named SmdA (for staphylococcal morphology determinant A), is a membrane protein with septum-enriched localization. By CRISPRi knockdown and overexpression combined with different microscopy techniques, we demonstrated that proper levels of SmdA were necessary for cell division, including septum formation and cell splitting. We also identified conserved residues in SmdA that were critical for its functionality. Pulldown and bacterial two-hybrid interaction experiments showed that SmdA interacted with several known cell division and cell wall synthesis proteins, including penicillin-binding proteins (PBPs) and EzrA. Notably, SmdA also affected susceptibility to cell wall targeting antibiotics, particularly in methicillin-resistant S. aureus (MRSA). Together, our results showed that S. aureus was dependent on balanced amounts of membrane attached SmdA to carry out proper cell division. IMPORTANCE Staphylococcus aureus is an important human and animal pathogen. Antibiotic resistance is a major problem in the treatment of staphylococcal infections, and cell division and cell wall synthesis factors have previously been shown to modulate susceptibility to antibiotics in this species. Here, we investigated the function of a protein named SmdA, which was identified based on its septal localization and knockdown phenotype resulting in defective cellular morphologies. We demonstrated that this protein was critical for normal cell division in S. aureus. Depletion of SmdA sensitized resistant staphylococci to β-lactam antibiotics. This work revealed a new staphylococcal cell division factor and a potential future target for narrow-spectrum antimicrobials or compounds to resensitize antibiotic-resistant staphylococcal strains.https://journals.asm.org/doi/10.1128/mbio.03404-21cell biologycell divisioncell wallsubcellular localization |
| spellingShingle | Ine Storaker Myrbråten Gro Anita Stamsås Helena Chan Danae Morales Angeles Tiril Mathiesen Knutsen Zhian Salehian Volha Shapaval Daniel Straume Morten Kjos SmdA is a Novel Cell Morphology Determinant in Staphylococcus aureus mBio cell biology cell division cell wall subcellular localization |
| title | SmdA is a Novel Cell Morphology Determinant in Staphylococcus aureus |
| title_full | SmdA is a Novel Cell Morphology Determinant in Staphylococcus aureus |
| title_fullStr | SmdA is a Novel Cell Morphology Determinant in Staphylococcus aureus |
| title_full_unstemmed | SmdA is a Novel Cell Morphology Determinant in Staphylococcus aureus |
| title_short | SmdA is a Novel Cell Morphology Determinant in Staphylococcus aureus |
| title_sort | smda is a novel cell morphology determinant in staphylococcus aureus |
| topic | cell biology cell division cell wall subcellular localization |
| url | https://journals.asm.org/doi/10.1128/mbio.03404-21 |
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