Academic Journal
4-Hydroxy-3-Methyl-2-Alkenylquinoline Disrupts Temporospatial Control of Flagellar Assembly and Induces Transcriptomic Remodeling in Bacillus subtilis Consistent with a Short-Circuiting of the Spo0A Phosphorelay.
| Title: | 4-Hydroxy-3-Methyl-2-Alkenylquinoline Disrupts Temporospatial Control of Flagellar Assembly and Induces Transcriptomic Remodeling in Bacillus subtilis Consistent with a Short-Circuiting of the Spo0A Phosphorelay. |
|---|---|
| Authors: | Williams MD; Department of Biology, Texas A&M University, College Station, TX 77843, USA.; Department of Biology, Prairie View A&M University, Prairie View, TX 77446, USA., Smith L; Department of Biology, Texas A&M University, College Station, TX 77843, USA.; Antimicrobial Division, Sano Chemicals Inc., Bryan, TX 77808, USA. |
| Source: | Molecules (Basel, Switzerland) [Molecules] 2026 Sep 12; Vol. 31 (18). Date of Electronic Publication: 2026 Sep 12. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: MDPI Country of Publication: Switzerland NLM ID: 100964009 Publication Model: Electronic Cited Medium: Internet ISSN: 1420-3049 (Electronic) Linking ISSN: 14203049 NLM ISO Abbreviation: Molecules Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Basel, Switzerland : MDPI, c1995- |
| MeSH Terms: | Bacillus subtilis*/drug effects , Bacillus subtilis*/genetics , Bacillus subtilis*/metabolism , Flagella*/drug effects , Flagella*/metabolism , Flagella*/genetics , Bacterial Proteins*/metabolism , Bacterial Proteins*/genetics , Transcription Factors*/metabolism , Transcription Factors*/genetics , Transcriptome*/drug effects , Quinolines*/pharmacology , Quinolines*/chemistry, Gene Expression Regulation, Bacterial/drug effects ; Phosphorylation/drug effects |
| Abstract: | 4-hydroxy-3-methyl-2-alkenylquinolines (HMAQs) belong to an emerging sub-class of naturally synthesized alkaloids with several prominent biological properties. HMAQ-7 is a novel variant recently identified in Burkholderia contaminans MS14 which was previously shown to impede normal cellular behaviors in Bacillus subtilis, including multiple colonization phenotypes such as motility, pellicle formation, and sporulation. While the list of biological and chemical characteristics among HMAQ's and related molecules is extensive, the mechanistic basis of these responses has been far more elusive. Using a combination of RNA-seq and bioinformatics, we have determined that several of the physiological defects induced by HMAQ-7 are strongly correlated with alterations in systems related to phospho-transduction. Specifically, HMAQ-7 augments gene expression in elements associated with late stationary phase growth, including those involved in phosphate assimilation and regulation of the spo0A phosphorelay. We also note that HMAQ-7 promotes dysregulated transcription of flagellar assembly genes which would normally be downregulated during late stationary phase. This study constitutes one of the first extensive investigations into an HMAQ's mode of action, providing vital insight into the ecological dynamics between B. contaminans and B. subtilis. |
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| Grant Information: | R41 AI131792 United States AI NIAID NIH HHS; R42 AI131792 United States AI NIAID NIH HHS; R41AI131792 National Institute of Allergy and Infectious Diseases; R42AI131792 National Institute of Allergy and Infectious Diseases |
| Contributed Indexing: | Keywords: Bacillus subtilis; Burkholderia; Spo0A; alkaloid; anti-biofilm; anti-sporulation; antimicrobial; flagella; quinolone |
| Substance Nomenclature: | 0 (Bacterial Proteins) 0 (Spo0A protein, Bacillus subtilis) 0 (Transcription Factors) 0 (Quinolines) |
| Entry Date(s): | Date Created: 20260926 Date Completed: 20260926 Latest Revision: 20260930 |
| Update Code: | 20260930 |
| PubMed Central ID: | PMC13609334 |
| DOI: | 10.3390/molecules31183226 |
| PMID: | 42796513 |
| Database: | MEDLINE |
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| Items | – Name: Title Label: Title Group: Ti Data: 4-Hydroxy-3-Methyl-2-Alkenylquinoline Disrupts Temporospatial Control of Flagellar Assembly and Induces Transcriptomic Remodeling in Bacillus subtilis Consistent with a Short-Circuiting of the Spo0A Phosphorelay. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AU" term="%22Williams+MD%22">Williams MD</searchLink>; Department of Biology, Texas A&M University, College Station, TX 77843, USA.; Department of Biology, Prairie View A&M University, Prairie View, TX 77446, USA.<br /><searchLink fieldCode="AU" term="%22Smith+L%22">Smith L</searchLink>; Department of Biology, Texas A&M University, College Station, TX 77843, USA.; Antimicrobial Division, Sano Chemicals Inc., Bryan, TX 77808, USA. – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22100964009%22">Molecules (Basel, Switzerland)</searchLink> [Molecules] 2026 Sep 12; Vol. 31 (18). <i>Date of Electronic Publication: </i>2026 Sep 12. – Name: TypePub Label: Publication Type Group: TypPub Data: Journal Article – Name: Language Label: Language Group: Lang Data: English – Name: TitleSource Label: Journal Info Group: Src Data: <i>Publisher: </i><searchLink fieldCode="PB" term="%22MDPI%22">MDPI </searchLink><i>Country of Publication: </i>Switzerland <i>NLM ID: </i>100964009 <i>Publication Model: </i>Electronic <i>Cited Medium: </i>Internet <i>ISSN: </i>1420-3049 (Electronic) <i>Linking ISSN: </i><searchLink fieldCode="IS" term="%2214203049%22">14203049 </searchLink><i>NLM ISO Abbreviation: </i>Molecules <i>Subsets: </i>MEDLINE – Name: PublisherInfo Label: Imprint Name(s) Group: PubInfo Data: <i>Original Publication</i>: Basel, Switzerland : MDPI, c1995- – Name: SubjectMESH Label: MeSH Terms Group: Su Data: <searchLink fieldCode="MM" term="%22Bacillus+subtilis%22">Bacillus subtilis*</searchLink>/<searchLink fieldCode="MM" term="%22Bacillus+subtilis+drug+effects%22">drug effects</searchLink> <br /><searchLink fieldCode="MM" term="%22Bacillus+subtilis%22">Bacillus subtilis*</searchLink>/<searchLink fieldCode="MM" term="%22Bacillus+subtilis+genetics%22">genetics</searchLink> <br /><searchLink fieldCode="MM" term="%22Bacillus+subtilis%22">Bacillus subtilis*</searchLink>/<searchLink fieldCode="MM" term="%22Bacillus+subtilis+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Flagella%22">Flagella*</searchLink>/<searchLink fieldCode="MM" term="%22Flagella+drug+effects%22">drug effects</searchLink> <br /><searchLink fieldCode="MM" term="%22Flagella%22">Flagella*</searchLink>/<searchLink fieldCode="MM" term="%22Flagella+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Flagella%22">Flagella*</searchLink>/<searchLink fieldCode="MM" term="%22Flagella+genetics%22">genetics</searchLink> <br /><searchLink fieldCode="MM" term="%22Bacterial+Proteins%22">Bacterial Proteins*</searchLink>/<searchLink fieldCode="MM" term="%22Bacterial+Proteins+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Bacterial+Proteins%22">Bacterial Proteins*</searchLink>/<searchLink fieldCode="MM" term="%22Bacterial+Proteins+genetics%22">genetics</searchLink> <br /><searchLink fieldCode="MM" term="%22Transcription+Factors%22">Transcription Factors*</searchLink>/<searchLink fieldCode="MM" term="%22Transcription+Factors+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Transcription+Factors%22">Transcription Factors*</searchLink>/<searchLink fieldCode="MM" term="%22Transcription+Factors+genetics%22">genetics</searchLink> <br /><searchLink fieldCode="MM" term="%22Transcriptome%22">Transcriptome*</searchLink>/<searchLink fieldCode="MM" term="%22Transcriptome+drug+effects%22">drug effects</searchLink> <br /><searchLink fieldCode="MM" term="%22Quinolines%22">Quinolines*</searchLink>/<searchLink fieldCode="MM" term="%22Quinolines+pharmacology%22">pharmacology</searchLink> <br /><searchLink fieldCode="MM" term="%22Quinolines%22">Quinolines*</searchLink>/<searchLink fieldCode="MM" term="%22Quinolines+chemistry%22">chemistry</searchLink><br /><searchLink fieldCode="MH" term="%22Gene+Expression+Regulation%2C+Bacterial%22">Gene Expression Regulation, Bacterial</searchLink>/<searchLink fieldCode="MH" term="%22Gene+Expression+Regulation%2C+Bacterial+drug+effects%22">drug effects</searchLink> ; <searchLink fieldCode="MH" term="%22Phosphorylation%22">Phosphorylation</searchLink>/<searchLink fieldCode="MH" term="%22Phosphorylation+drug+effects%22">drug effects</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: 4-hydroxy-3-methyl-2-alkenylquinolines (HMAQs) belong to an emerging sub-class of naturally synthesized alkaloids with several prominent biological properties. HMAQ-7 is a novel variant recently identified in Burkholderia contaminans MS14 which was previously shown to impede normal cellular behaviors in Bacillus subtilis, including multiple colonization phenotypes such as motility, pellicle formation, and sporulation. While the list of biological and chemical characteristics among HMAQ's and related molecules is extensive, the mechanistic basis of these responses has been far more elusive. Using a combination of RNA-seq and bioinformatics, we have determined that several of the physiological defects induced by HMAQ-7 are strongly correlated with alterations in systems related to phospho-transduction. Specifically, HMAQ-7 augments gene expression in elements associated with late stationary phase growth, including those involved in phosphate assimilation and regulation of the spo0A phosphorelay. We also note that HMAQ-7 promotes dysregulated transcription of flagellar assembly genes which would normally be downregulated during late stationary phase. This study constitutes one of the first extensive investigations into an HMAQ's mode of action, providing vital insight into the ecological dynamics between B. contaminans and B. subtilis. – Name: Ref Label: References Group: RefInfo Data: Antibiotics (Basel). 2021 Feb 02;10(2):. (PMID: <searchLink fieldCode="PM" term="%2233540653%22">33540653)</searchLink><br />J Nat Prod. 2013 Feb 22;76(2):150-6. (PMID: <searchLink fieldCode="PM" term="%2223394257%22">23394257)</searchLink><br />Chem Biol. 2007 Jan;14(1):87-96. (PMID: <searchLink fieldCode="PM" term="%2217254955%22">17254955)</searchLink><br />Proc Natl Acad Sci U S A. 2010 May 4;107(18):8486-91. (PMID: <searchLink fieldCode="PM" term="%2220404177%22">20404177)</searchLink><br />Mol Microbiol. 2015 Apr;96(2):325-48. 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(PMID: <searchLink fieldCode="PM" term="%221569009%22">1569009)</searchLink> – Name: GrantInfo Label: Grant Information Group: Grant Data: R41 AI131792 United States AI NIAID NIH HHS; R42 AI131792 United States AI NIAID NIH HHS; R41AI131792 National Institute of Allergy and Infectious Diseases; R42AI131792 National Institute of Allergy and Infectious Diseases – Name: SubjectMinor Label: Contributed Indexing Group: Data: <i>Keywords: </i>Bacillus subtilis; Burkholderia; Spo0A; alkaloid; anti-biofilm; anti-sporulation; antimicrobial; flagella; quinolone – Name: NumberCAS Label: Substance Nomenclature Group: ID Data: 0 (Bacterial Proteins)<br />0 (Spo0A protein, Bacillus subtilis)<br />0 (Transcription Factors)<br />0 (Quinolines) – Name: DateEntry Label: Entry Date(s) Group: Date Data: <i>Date Created: </i>20260926 <i>Date Completed: </i>20260926 <i>Latest Revision: </i>20260930 – Name: DateUpdate Label: Update Code Group: Date Data: 20260930 – Name: PubmedCentralID Label: PubMed Central ID Group: ID Data: PMC13609334 – Name: DOI Label: DOI Group: ID Data: 10.3390/molecules31183226 – Name: AN Label: PMID Group: ID Data: 42796513 |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.3390/molecules31183226 Languages: – Code: eng Text: English Subjects: – SubjectFull: Gene Expression Regulation, Bacterial drug effects Type: general – SubjectFull: Phosphorylation drug effects Type: general – SubjectFull: Bacillus subtilis drug effects Type: general – SubjectFull: Bacillus subtilis genetics Type: general – SubjectFull: Bacillus subtilis metabolism Type: general – SubjectFull: Flagella drug effects Type: general – SubjectFull: Flagella metabolism Type: general – SubjectFull: Flagella genetics Type: general – SubjectFull: Bacterial Proteins metabolism Type: general – SubjectFull: Bacterial Proteins genetics Type: general – SubjectFull: Transcription Factors metabolism Type: general – SubjectFull: Transcription Factors genetics Type: general – SubjectFull: Transcriptome drug effects Type: general – SubjectFull: Quinolines pharmacology Type: general – SubjectFull: Quinolines chemistry Type: general Titles: – TitleFull: 4-Hydroxy-3-Methyl-2-Alkenylquinoline Disrupts Temporospatial Control of Flagellar Assembly and Induces Transcriptomic Remodeling in Bacillus subtilis Consistent with a Short-Circuiting of the Spo0A Phosphorelay. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Williams MD – PersonEntity: Name: NameFull: Smith L IsPartOfRelationships: – BibEntity: Dates: – D: 12 M: 09 Text: 2026 Sep 12 Type: published Y: 2026 Identifiers: – Type: issn-electronic Value: 1420-3049 Numbering: – Type: volume Value: 31 – Type: issue Value: 18 Titles: – TitleFull: Molecules (Basel, Switzerland) Type: main |
| ResultId | 1 |