A Predicted Helix-Turn-Helix Core Is Critical for Bacteriophage Kil Peptide to Disrupt <i>Escherichia coli</i> Cell Division
<b>Background/objectives</b>: FtsZ, a eukaryotic tubulin homolog and an essential component of the bacterial divisome, is the target of numerous antimicrobial compounds as well as proteins and peptides, most of which inhibit FtsZ polymerization dynamics. We previously showed that the Kil...
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2025-01-01
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| author | Arindam Naha Todd A. Cameron William Margolin |
| author_facet | Arindam Naha Todd A. Cameron William Margolin |
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| description | <b>Background/objectives</b>: FtsZ, a eukaryotic tubulin homolog and an essential component of the bacterial divisome, is the target of numerous antimicrobial compounds as well as proteins and peptides, most of which inhibit FtsZ polymerization dynamics. We previously showed that the Kil peptide from bacteriophage λ inhibits <i>Escherichia coli</i> cell division by disrupting FtsZ ring assembly, and this inhibition requires the presence of the essential FtsZ membrane anchor protein ZipA. <b>Methods</b>: To investigate Kil’s molecular mechanism further, we employed deletions, truncations, and molecular modeling to identify the minimal residues necessary for its activity. <b>Results</b>: Modeling suggested that Kil’s core segment folds into a helix-turn-helix (HTH) structure. Deleting either the C-terminal 11 residues or the N-terminal 5 residues of Kil still allowed the inhibition of <i>E. coli</i> cell division, but removing both termini nearly abolished this activity, indicating that a minimal region within the Kil HTH core is essential for its structure and function. Another Kil-like peptide from a closely related enterobacterial phage also disrupted FtsZ ring assembly and required ZipA for this activity. Consistent with its broader activity against FtsZ, λ Kil was able to efficiently inhibit cell division of a uropathogenic <i>E. coli</i> (UPEC) strain. <b>Conclusions</b>: Understanding the structure and function of Kil and similar peptides can potentially reveal additional ways to target FtsZ for antimicrobial therapies and elucidate how FtsZ functions in bacterial cell division. |
| format | Article |
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| institution | Kabale University |
| issn | 2079-6382 |
| language | English |
| publishDate | 2025-01-01 |
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| spelling | doaj-art-b8c19b5dbaa14b86801de3c6b634f59b2025-01-24T13:18:45ZengMDPI AGAntibiotics2079-63822025-01-011415210.3390/antibiotics14010052A Predicted Helix-Turn-Helix Core Is Critical for Bacteriophage Kil Peptide to Disrupt <i>Escherichia coli</i> Cell DivisionArindam Naha0Todd A. Cameron1William Margolin2Department of Microbiology and Molecular Genetics, UTHealth-Houston, Houston, TX 77030, USADepartment of Microbiology and Molecular Genetics, UTHealth-Houston, Houston, TX 77030, USADepartment of Microbiology and Molecular Genetics, UTHealth-Houston, Houston, TX 77030, USA<b>Background/objectives</b>: FtsZ, a eukaryotic tubulin homolog and an essential component of the bacterial divisome, is the target of numerous antimicrobial compounds as well as proteins and peptides, most of which inhibit FtsZ polymerization dynamics. We previously showed that the Kil peptide from bacteriophage λ inhibits <i>Escherichia coli</i> cell division by disrupting FtsZ ring assembly, and this inhibition requires the presence of the essential FtsZ membrane anchor protein ZipA. <b>Methods</b>: To investigate Kil’s molecular mechanism further, we employed deletions, truncations, and molecular modeling to identify the minimal residues necessary for its activity. <b>Results</b>: Modeling suggested that Kil’s core segment folds into a helix-turn-helix (HTH) structure. Deleting either the C-terminal 11 residues or the N-terminal 5 residues of Kil still allowed the inhibition of <i>E. coli</i> cell division, but removing both termini nearly abolished this activity, indicating that a minimal region within the Kil HTH core is essential for its structure and function. Another Kil-like peptide from a closely related enterobacterial phage also disrupted FtsZ ring assembly and required ZipA for this activity. Consistent with its broader activity against FtsZ, λ Kil was able to efficiently inhibit cell division of a uropathogenic <i>E. coli</i> (UPEC) strain. <b>Conclusions</b>: Understanding the structure and function of Kil and similar peptides can potentially reveal additional ways to target FtsZ for antimicrobial therapies and elucidate how FtsZ functions in bacterial cell division.https://www.mdpi.com/2079-6382/14/1/52cell divisionFtsZbacteriophagedivisomeantibiotic |
| spellingShingle | Arindam Naha Todd A. Cameron William Margolin A Predicted Helix-Turn-Helix Core Is Critical for Bacteriophage Kil Peptide to Disrupt <i>Escherichia coli</i> Cell Division Antibiotics cell division FtsZ bacteriophage divisome antibiotic |
| title | A Predicted Helix-Turn-Helix Core Is Critical for Bacteriophage Kil Peptide to Disrupt <i>Escherichia coli</i> Cell Division |
| title_full | A Predicted Helix-Turn-Helix Core Is Critical for Bacteriophage Kil Peptide to Disrupt <i>Escherichia coli</i> Cell Division |
| title_fullStr | A Predicted Helix-Turn-Helix Core Is Critical for Bacteriophage Kil Peptide to Disrupt <i>Escherichia coli</i> Cell Division |
| title_full_unstemmed | A Predicted Helix-Turn-Helix Core Is Critical for Bacteriophage Kil Peptide to Disrupt <i>Escherichia coli</i> Cell Division |
| title_short | A Predicted Helix-Turn-Helix Core Is Critical for Bacteriophage Kil Peptide to Disrupt <i>Escherichia coli</i> Cell Division |
| title_sort | predicted helix turn helix core is critical for bacteriophage kil peptide to disrupt i escherichia coli i cell division |
| topic | cell division FtsZ bacteriophage divisome antibiotic |
| url | https://www.mdpi.com/2079-6382/14/1/52 |
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