Antibiofilm Activities of Halogenated Pyrimidines Against Enterohemorrhagic Escherichia coli O157:H7.
| Title: | Antibiofilm Activities of Halogenated Pyrimidines Against Enterohemorrhagic Escherichia coli O157:H7. |
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| Authors: | Jeon, Hyejin1 (AUTHOR) hyejin7882@ynu.ac.kr, Kim, Yong-Guy1 (AUTHOR), Lee, Jin-Hyung1 (AUTHOR) jinhlee@ynu.ac.kr, Lee, Jintae1 (AUTHOR) jinhlee@ynu.ac.kr |
| Source: | International Journal of Molecular Sciences. Feb2025, Vol. 26 Issue 3, p1386. 14p. |
| Subject Terms: | *ESCHERICHIA coli O157:H7, *PYRIMIDINE derivatives, *DRUG resistance in bacteria, *PUBLIC health, *ESCHERICHIA coli, *BACTERIAL adhesion |
| Abstract: | Enterohemorrhagic Escherichia coli (EHEC) is a significant public health concern due to its ability to form biofilms, enhancing its resistance to antimicrobials and contributing to its persistence in food processing environments. Traditional antibiotics often fail to target these biofilms effectively, leading to increased bacterial resistance. This study aims to explore the efficacy of novel antibiofilm agents, specifically halogenated pyrimidine derivatives, against EHEC. We screened pyrimidine and 31 halogenated pyrimidine derivatives for their antimicrobial and antibiofilm activities against EHEC using biofilm quantification assays, SEM analysis, motility, and curli production assessments. Our findings reveal that certain halogenated pyrimidine derivatives, notably 2-amino-5-bromopyrimidine (2A5BP), 2-amino-4-chloropyrrolo[2,3-d]pyrimidine (2A4CPP), and 2,4-dichloro-5-iodo-7H-pyrrolo[2,3-d]pyrimidine (2,4DC5IPP) at 50 µg/mL, exhibited significant inhibitory effects on EHEC biofilm formation without affecting bacterial growth, suggesting a targeted antibiofilm action. These compounds effectively reduced curli production and EHEC motility, essential factors for biofilm integrity and development. qRT-PCR analysis revealed that two active compounds downregulated the expression of key curli genes (csgA and csgB), leading to reduced bacterial adhesion and biofilm formation. Additionally, in silico ADME–Tox profiles indicated that these compounds exhibit favorable drug-like properties and lower toxicity compared with traditional pyrimidine. This study highlights the potential of halogenated pyrimidine derivatives as effective antibiofilm agents against EHEC, offering a promising strategy for enhancing food safety and controlling EHEC infections. The distinct mechanisms of action of these compounds, particularly in inhibiting biofilm formation and virulence factors without promoting bacterial resistance, underscore their therapeutic potential. [ABSTRACT FROM AUTHOR] |
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| Items | – Name: Title Label: Title Group: Ti Data: Antibiofilm Activities of Halogenated Pyrimidines Against Enterohemorrhagic Escherichia coli O157:H7. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Jeon%2C+Hyejin%22">Jeon, Hyejin</searchLink><relatesTo>1</relatesTo> (AUTHOR)<i> hyejin7882@ynu.ac.kr</i><br /><searchLink fieldCode="AR" term="%22Kim%2C+Yong-Guy%22">Kim, Yong-Guy</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Lee%2C+Jin-Hyung%22">Lee, Jin-Hyung</searchLink><relatesTo>1</relatesTo> (AUTHOR)<i> jinhlee@ynu.ac.kr</i><br /><searchLink fieldCode="AR" term="%22Lee%2C+Jintae%22">Lee, Jintae</searchLink><relatesTo>1</relatesTo> (AUTHOR)<i> jinhlee@ynu.ac.kr</i> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22International+Journal+of+Molecular+Sciences%22">International Journal of Molecular Sciences</searchLink>. Feb2025, Vol. 26 Issue 3, p1386. 14p. – Name: Subject Label: Subject Terms Group: Su Data: *<searchLink fieldCode="DE" term="%22ESCHERICHIA+coli+O157%3AH7%22">ESCHERICHIA coli O157:H7</searchLink><br />*<searchLink fieldCode="DE" term="%22PYRIMIDINE+derivatives%22">PYRIMIDINE derivatives</searchLink><br />*<searchLink fieldCode="DE" term="%22DRUG+resistance+in+bacteria%22">DRUG resistance in bacteria</searchLink><br />*<searchLink fieldCode="DE" term="%22PUBLIC+health%22">PUBLIC health</searchLink><br />*<searchLink fieldCode="DE" term="%22ESCHERICHIA+coli%22">ESCHERICHIA coli</searchLink><br />*<searchLink fieldCode="DE" term="%22BACTERIAL+adhesion%22">BACTERIAL adhesion</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Enterohemorrhagic Escherichia coli (EHEC) is a significant public health concern due to its ability to form biofilms, enhancing its resistance to antimicrobials and contributing to its persistence in food processing environments. Traditional antibiotics often fail to target these biofilms effectively, leading to increased bacterial resistance. This study aims to explore the efficacy of novel antibiofilm agents, specifically halogenated pyrimidine derivatives, against EHEC. We screened pyrimidine and 31 halogenated pyrimidine derivatives for their antimicrobial and antibiofilm activities against EHEC using biofilm quantification assays, SEM analysis, motility, and curli production assessments. Our findings reveal that certain halogenated pyrimidine derivatives, notably 2-amino-5-bromopyrimidine (2A5BP), 2-amino-4-chloropyrrolo[2,3-d]pyrimidine (2A4CPP), and 2,4-dichloro-5-iodo-7H-pyrrolo[2,3-d]pyrimidine (2,4DC5IPP) at 50 µg/mL, exhibited significant inhibitory effects on EHEC biofilm formation without affecting bacterial growth, suggesting a targeted antibiofilm action. These compounds effectively reduced curli production and EHEC motility, essential factors for biofilm integrity and development. qRT-PCR analysis revealed that two active compounds downregulated the expression of key curli genes (csgA and csgB), leading to reduced bacterial adhesion and biofilm formation. Additionally, in silico ADME–Tox profiles indicated that these compounds exhibit favorable drug-like properties and lower toxicity compared with traditional pyrimidine. This study highlights the potential of halogenated pyrimidine derivatives as effective antibiofilm agents against EHEC, offering a promising strategy for enhancing food safety and controlling EHEC infections. The distinct mechanisms of action of these compounds, particularly in inhibiting biofilm formation and virulence factors without promoting bacterial resistance, underscore their therapeutic potential. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of International Journal of Molecular Sciences is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.3390/ijms26031386 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 14 StartPage: 1386 Subjects: – SubjectFull: ESCHERICHIA coli O157:H7 Type: general – SubjectFull: PYRIMIDINE derivatives Type: general – SubjectFull: DRUG resistance in bacteria Type: general – SubjectFull: PUBLIC health Type: general – SubjectFull: ESCHERICHIA coli Type: general – SubjectFull: BACTERIAL adhesion Type: general Titles: – TitleFull: Antibiofilm Activities of Halogenated Pyrimidines Against Enterohemorrhagic Escherichia coli O157:H7. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Jeon, Hyejin – PersonEntity: Name: NameFull: Kim, Yong-Guy – PersonEntity: Name: NameFull: Lee, Jin-Hyung – PersonEntity: Name: NameFull: Lee, Jintae IsPartOfRelationships: – BibEntity: Dates: – D: 01 M: 02 Text: Feb2025 Type: published Y: 2025 Identifiers: – Type: issn-print Value: 16616596 Numbering: – Type: volume Value: 26 – Type: issue Value: 3 Titles: – TitleFull: International Journal of Molecular Sciences Type: main |
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