The Cell Wall Polymer Lipoteichoic Acid Becomes Nonessential in <named-content content-type="genus-species">Staphylococcus aureus</named-content> Cells Lacking the ClpX Chaperone
ABSTRACT Lipoteichoic acid (LTA) is an important cell wall component of Gram-positive bacteria and a promising target for the development of vaccines and antimicrobial compounds against Staphylococcus aureus. Here we demonstrate that mutations in the conditionally essential ltaS (LTA synthase) gene...
Guardado en:
| Autores principales: | , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
American Society for Microbiology
2016
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/81bf6ed8bfd14486bbbac2d2d6e30f94 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:81bf6ed8bfd14486bbbac2d2d6e30f94 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:81bf6ed8bfd14486bbbac2d2d6e30f942021-11-15T15:50:18ZThe Cell Wall Polymer Lipoteichoic Acid Becomes Nonessential in <named-content content-type="genus-species">Staphylococcus aureus</named-content> Cells Lacking the ClpX Chaperone10.1128/mBio.01228-162150-7511https://doaj.org/article/81bf6ed8bfd14486bbbac2d2d6e30f942016-09-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01228-16https://doaj.org/toc/2150-7511ABSTRACT Lipoteichoic acid (LTA) is an important cell wall component of Gram-positive bacteria and a promising target for the development of vaccines and antimicrobial compounds against Staphylococcus aureus. Here we demonstrate that mutations in the conditionally essential ltaS (LTA synthase) gene arise spontaneously in an S. aureus mutant lacking the ClpX chaperone. A wide variety of ltaS mutations were selected, and among these, a substantial portion resulted in premature stop codons and other changes predicted to abolish LtaS synthesis. Consistent with this assumption, the clpX ltaS double mutants did not produce LTA, and genetic analyses confirmed that LTA becomes nonessential in the absence of the ClpX chaperone. In fact, inactivation of ltaS alleviated the severe growth defect conferred by the clpX deletion. Microscopic analyses showed that the absence of ClpX partly alleviates the septum placement defects of an LTA-depleted strain, while other phenotypes typical of LTA-negative S. aureus mutants, including increased cell size and decreased autolytic activity, are retained. In conclusion, our results indicate that LTA has an essential role in septum placement that can be bypassed by inactivating the ClpX chaperone. IMPORTANCE Lipoteichoic acid is an essential component of the Staphylococcus aureus cell envelope and an attractive target for the development of vaccines and antimicrobials directed against antibiotic-resistant Gram-positive bacteria such as methicillin-resistant S. aureus and vancomycin-resistant enterococci. In this study, we showed that the lipoteichoic acid polymer is essential for growth of S. aureus only as long as the ClpX chaperone is present in the cell. Our results indicate that lipoteichoic acid and ClpX play opposite roles in a pathway that controls two key cell division processes in S. aureus, namely, septum formation and autolytic activity. The discovery of a novel functional connection in the genetic network that controls cell division in S. aureus may expand the repertoire of possible strategies to identify compounds or compound combinations that kill antibiotic-resistant S. aureus.Kristoffer T. BækLisa BowmanCharlotte MillershipMia Dupont SøgaardVolkhard KaeverPia SiljamäkiKirsi SavijokiPekka VarmanenTuula A. NymanAngelika GründlingDorte FreesAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 7, Iss 4 (2016) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Microbiology QR1-502 |
| spellingShingle |
Microbiology QR1-502 Kristoffer T. Bæk Lisa Bowman Charlotte Millership Mia Dupont Søgaard Volkhard Kaever Pia Siljamäki Kirsi Savijoki Pekka Varmanen Tuula A. Nyman Angelika Gründling Dorte Frees The Cell Wall Polymer Lipoteichoic Acid Becomes Nonessential in <named-content content-type="genus-species">Staphylococcus aureus</named-content> Cells Lacking the ClpX Chaperone |
| description |
ABSTRACT Lipoteichoic acid (LTA) is an important cell wall component of Gram-positive bacteria and a promising target for the development of vaccines and antimicrobial compounds against Staphylococcus aureus. Here we demonstrate that mutations in the conditionally essential ltaS (LTA synthase) gene arise spontaneously in an S. aureus mutant lacking the ClpX chaperone. A wide variety of ltaS mutations were selected, and among these, a substantial portion resulted in premature stop codons and other changes predicted to abolish LtaS synthesis. Consistent with this assumption, the clpX ltaS double mutants did not produce LTA, and genetic analyses confirmed that LTA becomes nonessential in the absence of the ClpX chaperone. In fact, inactivation of ltaS alleviated the severe growth defect conferred by the clpX deletion. Microscopic analyses showed that the absence of ClpX partly alleviates the septum placement defects of an LTA-depleted strain, while other phenotypes typical of LTA-negative S. aureus mutants, including increased cell size and decreased autolytic activity, are retained. In conclusion, our results indicate that LTA has an essential role in septum placement that can be bypassed by inactivating the ClpX chaperone. IMPORTANCE Lipoteichoic acid is an essential component of the Staphylococcus aureus cell envelope and an attractive target for the development of vaccines and antimicrobials directed against antibiotic-resistant Gram-positive bacteria such as methicillin-resistant S. aureus and vancomycin-resistant enterococci. In this study, we showed that the lipoteichoic acid polymer is essential for growth of S. aureus only as long as the ClpX chaperone is present in the cell. Our results indicate that lipoteichoic acid and ClpX play opposite roles in a pathway that controls two key cell division processes in S. aureus, namely, septum formation and autolytic activity. The discovery of a novel functional connection in the genetic network that controls cell division in S. aureus may expand the repertoire of possible strategies to identify compounds or compound combinations that kill antibiotic-resistant S. aureus. |
| format |
article |
| author |
Kristoffer T. Bæk Lisa Bowman Charlotte Millership Mia Dupont Søgaard Volkhard Kaever Pia Siljamäki Kirsi Savijoki Pekka Varmanen Tuula A. Nyman Angelika Gründling Dorte Frees |
| author_facet |
Kristoffer T. Bæk Lisa Bowman Charlotte Millership Mia Dupont Søgaard Volkhard Kaever Pia Siljamäki Kirsi Savijoki Pekka Varmanen Tuula A. Nyman Angelika Gründling Dorte Frees |
| author_sort |
Kristoffer T. Bæk |
| title |
The Cell Wall Polymer Lipoteichoic Acid Becomes Nonessential in <named-content content-type="genus-species">Staphylococcus aureus</named-content> Cells Lacking the ClpX Chaperone |
| title_short |
The Cell Wall Polymer Lipoteichoic Acid Becomes Nonessential in <named-content content-type="genus-species">Staphylococcus aureus</named-content> Cells Lacking the ClpX Chaperone |
| title_full |
The Cell Wall Polymer Lipoteichoic Acid Becomes Nonessential in <named-content content-type="genus-species">Staphylococcus aureus</named-content> Cells Lacking the ClpX Chaperone |
| title_fullStr |
The Cell Wall Polymer Lipoteichoic Acid Becomes Nonessential in <named-content content-type="genus-species">Staphylococcus aureus</named-content> Cells Lacking the ClpX Chaperone |
| title_full_unstemmed |
The Cell Wall Polymer Lipoteichoic Acid Becomes Nonessential in <named-content content-type="genus-species">Staphylococcus aureus</named-content> Cells Lacking the ClpX Chaperone |
| title_sort |
cell wall polymer lipoteichoic acid becomes nonessential in <named-content content-type="genus-species">staphylococcus aureus</named-content> cells lacking the clpx chaperone |
| publisher |
American Society for Microbiology |
| publishDate |
2016 |
| url |
https://doaj.org/article/81bf6ed8bfd14486bbbac2d2d6e30f94 |
| work_keys_str_mv |
AT kristoffertbæk thecellwallpolymerlipoteichoicacidbecomesnonessentialinnamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentcellslackingtheclpxchaperone AT lisabowman thecellwallpolymerlipoteichoicacidbecomesnonessentialinnamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentcellslackingtheclpxchaperone AT charlottemillership thecellwallpolymerlipoteichoicacidbecomesnonessentialinnamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentcellslackingtheclpxchaperone AT miadupontsøgaard thecellwallpolymerlipoteichoicacidbecomesnonessentialinnamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentcellslackingtheclpxchaperone AT volkhardkaever thecellwallpolymerlipoteichoicacidbecomesnonessentialinnamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentcellslackingtheclpxchaperone AT piasiljamaki thecellwallpolymerlipoteichoicacidbecomesnonessentialinnamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentcellslackingtheclpxchaperone AT kirsisavijoki thecellwallpolymerlipoteichoicacidbecomesnonessentialinnamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentcellslackingtheclpxchaperone AT pekkavarmanen thecellwallpolymerlipoteichoicacidbecomesnonessentialinnamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentcellslackingtheclpxchaperone AT tuulaanyman thecellwallpolymerlipoteichoicacidbecomesnonessentialinnamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentcellslackingtheclpxchaperone AT angelikagrundling thecellwallpolymerlipoteichoicacidbecomesnonessentialinnamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentcellslackingtheclpxchaperone AT dortefrees thecellwallpolymerlipoteichoicacidbecomesnonessentialinnamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentcellslackingtheclpxchaperone AT kristoffertbæk cellwallpolymerlipoteichoicacidbecomesnonessentialinnamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentcellslackingtheclpxchaperone AT lisabowman cellwallpolymerlipoteichoicacidbecomesnonessentialinnamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentcellslackingtheclpxchaperone AT charlottemillership cellwallpolymerlipoteichoicacidbecomesnonessentialinnamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentcellslackingtheclpxchaperone AT miadupontsøgaard cellwallpolymerlipoteichoicacidbecomesnonessentialinnamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentcellslackingtheclpxchaperone AT volkhardkaever cellwallpolymerlipoteichoicacidbecomesnonessentialinnamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentcellslackingtheclpxchaperone AT piasiljamaki cellwallpolymerlipoteichoicacidbecomesnonessentialinnamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentcellslackingtheclpxchaperone AT kirsisavijoki cellwallpolymerlipoteichoicacidbecomesnonessentialinnamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentcellslackingtheclpxchaperone AT pekkavarmanen cellwallpolymerlipoteichoicacidbecomesnonessentialinnamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentcellslackingtheclpxchaperone AT tuulaanyman cellwallpolymerlipoteichoicacidbecomesnonessentialinnamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentcellslackingtheclpxchaperone AT angelikagrundling cellwallpolymerlipoteichoicacidbecomesnonessentialinnamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentcellslackingtheclpxchaperone AT dortefrees cellwallpolymerlipoteichoicacidbecomesnonessentialinnamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentcellslackingtheclpxchaperone |
| _version_ |
1718427408898457600 |