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Monounsaturated fatty acid biosynthesis is critical for streptococcal envelope homeostasis and stress tolerance.

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Τίτλος: Monounsaturated fatty acid biosynthesis is critical for streptococcal envelope homeostasis and stress tolerance.
Συγγραφείς: Baker JL; Department of Biomaterial & Biomedical Sciences, OHSU School of Dentistry, Portland, Oregon, USA.; Department of Biomedical Engineering, OHSU School of Medicine, Portland, Oregon, USA., Tang J; Department of Biomaterial & Biomedical Sciences, OHSU School of Dentistry, Portland, Oregon, USA.; KCGIP, Knight Campus for Accelerating Scientific Impact, University of Oregon, Eugene, Oregon, USA., Guo M; Department of Biomaterial & Biomedical Sciences, OHSU School of Dentistry, Portland, Oregon, USA., Farias-da-Silva FF; Department of Biomaterial & Biomedical Sciences, OHSU School of Dentistry, Portland, Oregon, USA.; Department of Public Health, Pediatric Dentistry and Orthodontics, Faculdade de Odontologia de Piracicaba Universidade Estadual de Campinas, Piracicaba, São Paulo, Brazil., Barbisan M; Department of Biomaterial & Biomedical Sciences, OHSU School of Dentistry, Portland, Oregon, USA., Burnside M; Department of Biomaterial & Biomedical Sciences, OHSU School of Dentistry, Portland, Oregon, USA., Crofton K; Department of Biomaterial & Biomedical Sciences, OHSU School of Dentistry, Portland, Oregon, USA.; Department of Biology, Rollins College, Winter Park, Florida, USA., Williams S; Department of Biomaterial & Biomedical Sciences, OHSU School of Dentistry, Portland, Oregon, USA.; Adams School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA., Rao S; Department of Biomaterial & Biomedical Sciences, OHSU School of Dentistry, Portland, Oregon, USA.; Department of Statistics, Santa Clara University, Santa Clara, California, USA., Lee M; Department of Biomaterial & Biomedical Sciences, OHSU School of Dentistry, Portland, Oregon, USA.; Department of Biology, Oregon State University, Corvallis, Oregon, USA., Drucker SG; Department of Biomaterial & Biomedical Sciences, OHSU School of Dentistry, Portland, Oregon, USA.; Department of Biology, Scripps College, Claremont, California, USA., Kim D; Department of Biomaterial & Biomedical Sciences, OHSU School of Dentistry, Portland, Oregon, USA., Higashi D; Department of Biomaterial & Biomedical Sciences, OHSU School of Dentistry, Portland, Oregon, USA., Merritt J; Department of Biomaterial & Biomedical Sciences, OHSU School of Dentistry, Portland, Oregon, USA.; Department of Molecular Microbiology and Immunology, OHSU School of Medicine, Portland, Oregon, USA., Hirose Y; Department of Oral and Molecular Microbiology, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan., Veening J-W; Department of Fundamental Microbiology, Faculty of Biology & Medicine, University of Lausanne, Lausanne, Switzerland., Nizet V; Department of Pediatrics, UC San Diego School of Medicine, La Jolla, California, USA.; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California, USA.
Πηγή: Journal of bacteriology [J Bacteriol] 2026 Sep 17; Vol. 208 (9), pp. e0002626. Date of Electronic Publication: 2026 Aug 07.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: American Society for Microbiology Country of Publication: United States NLM ID: 2985120R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1098-5530 (Electronic) Linking ISSN: 00219193 NLM ISO Abbreviation: J Bacteriol Subsets: MEDLINE
Imprint Name(s): Original Publication: Washington, DC : American Society for Microbiology
Ιατρικοί όροι (MeSH): Streptococcus mutans*/metabolism , Streptococcus mutans*/genetics , Streptococcus mutans*/physiology , Fatty Acids, Monounsaturated*/metabolism , Streptococcus pneumoniae*/metabolism , Streptococcus pneumoniae*/genetics , Streptococcus pneumoniae*/physiology , Streptococcus pneumoniae*/pathogenicity , Streptococcus pyogenes*/metabolism , Streptococcus pyogenes*/genetics , Streptococcus pyogenes*/physiology , Streptococcus pyogenes*/pathogenicity , Homeostasis* , Stress, Physiological*, Cell Membrane/metabolism ; Humans ; Virulence ; Gene Deletion
Περίληψη: The genus Streptococcus contains some of the most important commensals and pathogens of the human microbiome. To obtain the fatty acids required for cell membranes, Streptococcus either produce fatty acids de novo through the fatty acid biosynthesis (fab) pathway or uptake host fatty acids through the fatty acid kinase (fak) pathway. Although both the fab and fak pathways represent potential therapeutic targets to prevent or treat infection, progress is limited because of an incomplete understanding of taxon-to-taxon variability in streptococcal lipid metabolism. Here, we examined the role of de novo monounsaturated fatty acid (MUFA) synthesis in physiology and virulence-associated traits in Streptococcus mutans, Streptococcus pyogenes, and Streptococcus pneumoniae, three major pathogens that cause disease at distinct body sites. In all three species, deletion of fabM abolished MUFA production and caused severe growth defects, decreased stress tolerance, increased antibiotic susceptibility, and defects in cell viability, morphology, and division. In S. mutans, loss of fabM also markedly reduced competence signaling and production of the mutacin IV bacteriocin. Deletion of fabM increased susceptibility to killing by human neutrophils in S. mutans and S. pneumoniae, but not S. pyogenes. Together, these findings illustrate that MUFA synthesis is broadly important for streptococcal physiology and cell membrane homeostasis, while its contribution to pathogenesis is strongly species- and context-dependent, providing leads to guide the development of novel therapeutic and/or preventative strategies.IMPORTANCEStreptococcus spp. exert profound effects on human health, with several species causing significant morbidity and mortality. Although streptococcal fatty acid biosynthesis and utilization are attractive metabolic targets for development of therapeutics, this opportunity is vexed by an incomplete understanding of taxon-to-taxon variability in lipid metabolism. In this study, the role of de novo monounsaturated fatty acid (MUFA) synthesis in physiology and virulence-associated traits was examined in Streptococcus mutans, Streptococcus pyogenes, and Streptococcus pneumoniae, three major pathogens that cause disease at distinct body sites. MUFA synthesis was important for stress and antibiotic tolerance across all three species, while its impact on virulence was species- and context-dependent. Overall, these discoveries provide leads to guide the development of novel therapeutic and/or preventative strategies.
Competing Interests: The authors declare no conflict of interest.
Σχόλια: Update of: bioRxiv. 2026 Jan 14:2026.01.14.699484. doi: 10.64898/2026.01.14.699484.. (PMID: 41648328)
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Grant Information: R25 GM154345 United States GM NIGMS NIH HHS; R00-DE029228 United States NH NIH HHS; UL1 TR002369 United States TR NCATS NIH HHS; 001 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior; R35-DE028252 United States NH NIH HHS; K99-DE029228 United States NH NIH HHS; R25-DE032536 United States NH NIH HHS; K99 DE029228 United States DE NIDCR NIH HHS; R25 DE032536 United States DE NIDCR NIH HHS; R35 DE028252 United States DE NIDCR NIH HHS; R25-GM154345 United States NH NIH HHS; R00 DE029228 United States DE NIDCR NIH HHS
Contributed Indexing: Keywords: Streptococcus; fatty acid biosynthesis
Substance Nomenclature: 0 (Fatty Acids, Monounsaturated)
Entry Date(s): Date Created: 20260807 Date Completed: 20260917 Latest Revision: 20260919
Update Code: 20260919
PubMed Central ID: PMC13584702
DOI: 10.1128/jb.00026-26
PMID: 42565831
Βάση Δεδομένων: MEDLINE
FullText Text:
  Availability: 0
Header DbId: cmedm
DbLabel: MEDLINE
An: 42565831
AccessLevel: 3
PubType: Academic Journal
PubTypeId: academicJournal
PreciseRelevancyScore: 0
IllustrationInfo
Items – Name: Title
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  Data: Monounsaturated fatty acid biosynthesis is critical for streptococcal envelope homeostasis and stress tolerance.
– Name: Author
  Label: Authors
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  Data: <searchLink fieldCode="AU" term="%22Baker+JL%22">Baker JL</searchLink>; Department of Biomaterial & Biomedical Sciences, OHSU School of Dentistry, Portland, Oregon, USA.; Department of Biomedical Engineering, OHSU School of Medicine, Portland, Oregon, USA.<br /><searchLink fieldCode="AU" term="%22Tang+J%22">Tang J</searchLink>; Department of Biomaterial & Biomedical Sciences, OHSU School of Dentistry, Portland, Oregon, USA.; KCGIP, Knight Campus for Accelerating Scientific Impact, University of Oregon, Eugene, Oregon, USA.<br /><searchLink fieldCode="AU" term="%22Guo+M%22">Guo M</searchLink>; Department of Biomaterial & Biomedical Sciences, OHSU School of Dentistry, Portland, Oregon, USA.<br /><searchLink fieldCode="AU" term="%22Farias-da-Silva+FF%22">Farias-da-Silva FF</searchLink>; Department of Biomaterial & Biomedical Sciences, OHSU School of Dentistry, Portland, Oregon, USA.; Department of Public Health, Pediatric Dentistry and Orthodontics, Faculdade de Odontologia de Piracicaba Universidade Estadual de Campinas, Piracicaba, São Paulo, Brazil.<br /><searchLink fieldCode="AU" term="%22Barbisan+M%22">Barbisan M</searchLink>; Department of Biomaterial & Biomedical Sciences, OHSU School of Dentistry, Portland, Oregon, USA.<br /><searchLink fieldCode="AU" term="%22Burnside+M%22">Burnside M</searchLink>; Department of Biomaterial & Biomedical Sciences, OHSU School of Dentistry, Portland, Oregon, USA.<br /><searchLink fieldCode="AU" term="%22Crofton+K%22">Crofton K</searchLink>; Department of Biomaterial & Biomedical Sciences, OHSU School of Dentistry, Portland, Oregon, USA.; Department of Biology, Rollins College, Winter Park, Florida, USA.<br /><searchLink fieldCode="AU" term="%22Williams+S%22">Williams S</searchLink>; Department of Biomaterial & Biomedical Sciences, OHSU School of Dentistry, Portland, Oregon, USA.; Adams School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.<br /><searchLink fieldCode="AU" term="%22Rao+S%22">Rao S</searchLink>; Department of Biomaterial & Biomedical Sciences, OHSU School of Dentistry, Portland, Oregon, USA.; Department of Statistics, Santa Clara University, Santa Clara, California, USA.<br /><searchLink fieldCode="AU" term="%22Lee+M%22">Lee M</searchLink>; Department of Biomaterial & Biomedical Sciences, OHSU School of Dentistry, Portland, Oregon, USA.; Department of Biology, Oregon State University, Corvallis, Oregon, USA.<br /><searchLink fieldCode="AU" term="%22Drucker+SG%22">Drucker SG</searchLink>; Department of Biomaterial & Biomedical Sciences, OHSU School of Dentistry, Portland, Oregon, USA.; Department of Biology, Scripps College, Claremont, California, USA.<br /><searchLink fieldCode="AU" term="%22Kim+D%22">Kim D</searchLink>; Department of Biomaterial & Biomedical Sciences, OHSU School of Dentistry, Portland, Oregon, USA.<br /><searchLink fieldCode="AU" term="%22Higashi+D%22">Higashi D</searchLink>; Department of Biomaterial & Biomedical Sciences, OHSU School of Dentistry, Portland, Oregon, USA.<br /><searchLink fieldCode="AU" term="%22Merritt+J%22">Merritt J</searchLink>; Department of Biomaterial & Biomedical Sciences, OHSU School of Dentistry, Portland, Oregon, USA.; Department of Molecular Microbiology and Immunology, OHSU School of Medicine, Portland, Oregon, USA.<br /><searchLink fieldCode="AU" term="%22Hirose+Y%22">Hirose Y</searchLink>; Department of Oral and Molecular Microbiology, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.<br /><searchLink fieldCode="AU" term="%22Veening+J-W%22">Veening J-W</searchLink>; Department of Fundamental Microbiology, Faculty of Biology & Medicine, University of Lausanne, Lausanne, Switzerland.<br /><searchLink fieldCode="AU" term="%22Nizet+V%22">Nizet V</searchLink>; Department of Pediatrics, UC San Diego School of Medicine, La Jolla, California, USA.; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California, USA.
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  Data: <searchLink fieldCode="JN" term="%222985120R%22">Journal of bacteriology</searchLink> [J Bacteriol] 2026 Sep 17; Vol. 208 (9), pp. e0002626. <i>Date of Electronic Publication: </i>2026 Aug 07.
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  Data: <i>Original Publication</i>: Washington, DC : American Society for Microbiology
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  Label: MeSH Terms
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  Data: <searchLink fieldCode="MM" term="%22Streptococcus+mutans%22">Streptococcus mutans*</searchLink>/<searchLink fieldCode="MM" term="%22Streptococcus+mutans+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Streptococcus+mutans%22">Streptococcus mutans*</searchLink>/<searchLink fieldCode="MM" term="%22Streptococcus+mutans+genetics%22">genetics</searchLink> <br /><searchLink fieldCode="MM" term="%22Streptococcus+mutans%22">Streptococcus mutans*</searchLink>/<searchLink fieldCode="MM" term="%22Streptococcus+mutans+physiology%22">physiology</searchLink> <br /><searchLink fieldCode="MM" term="%22Fatty+Acids%2C+Monounsaturated%22">Fatty Acids, Monounsaturated*</searchLink>/<searchLink fieldCode="MM" term="%22Fatty+Acids%2C+Monounsaturated+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Streptococcus+pneumoniae%22">Streptococcus pneumoniae*</searchLink>/<searchLink fieldCode="MM" term="%22Streptococcus+pneumoniae+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Streptococcus+pneumoniae%22">Streptococcus pneumoniae*</searchLink>/<searchLink fieldCode="MM" term="%22Streptococcus+pneumoniae+genetics%22">genetics</searchLink> <br /><searchLink fieldCode="MM" term="%22Streptococcus+pneumoniae%22">Streptococcus pneumoniae*</searchLink>/<searchLink fieldCode="MM" term="%22Streptococcus+pneumoniae+physiology%22">physiology</searchLink> <br /><searchLink fieldCode="MM" term="%22Streptococcus+pneumoniae%22">Streptococcus pneumoniae*</searchLink>/<searchLink fieldCode="MM" term="%22Streptococcus+pneumoniae+pathogenicity%22">pathogenicity</searchLink> <br /><searchLink fieldCode="MM" term="%22Streptococcus+pyogenes%22">Streptococcus pyogenes*</searchLink>/<searchLink fieldCode="MM" term="%22Streptococcus+pyogenes+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Streptococcus+pyogenes%22">Streptococcus pyogenes*</searchLink>/<searchLink fieldCode="MM" term="%22Streptococcus+pyogenes+genetics%22">genetics</searchLink> <br /><searchLink fieldCode="MM" term="%22Streptococcus+pyogenes%22">Streptococcus pyogenes*</searchLink>/<searchLink fieldCode="MM" term="%22Streptococcus+pyogenes+physiology%22">physiology</searchLink> <br /><searchLink fieldCode="MM" term="%22Streptococcus+pyogenes%22">Streptococcus pyogenes*</searchLink>/<searchLink fieldCode="MM" term="%22Streptococcus+pyogenes+pathogenicity%22">pathogenicity</searchLink> <br /><searchLink fieldCode="MM" term="%22Homeostasis%22">Homeostasis*</searchLink> <br /><searchLink fieldCode="MM" term="%22Stress%2C+Physiological%22">Stress, Physiological*</searchLink><br /><searchLink fieldCode="MH" term="%22Cell+Membrane%22">Cell Membrane</searchLink>/<searchLink fieldCode="MH" term="%22Cell+Membrane+metabolism%22">metabolism</searchLink> ; <searchLink fieldCode="MH" term="%22Humans%22">Humans</searchLink> ; <searchLink fieldCode="MH" term="%22Virulence%22">Virulence</searchLink> ; <searchLink fieldCode="MH" term="%22Gene+Deletion%22">Gene Deletion</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: The genus Streptococcus contains some of the most important commensals and pathogens of the human microbiome. To obtain the fatty acids required for cell membranes, Streptococcus either produce fatty acids de novo through the fatty acid biosynthesis (fab) pathway or uptake host fatty acids through the fatty acid kinase (fak) pathway. Although both the fab and fak pathways represent potential therapeutic targets to prevent or treat infection, progress is limited because of an incomplete understanding of taxon-to-taxon variability in streptococcal lipid metabolism. Here, we examined the role of de novo monounsaturated fatty acid (MUFA) synthesis in physiology and virulence-associated traits in Streptococcus mutans, Streptococcus pyogenes, and Streptococcus pneumoniae, three major pathogens that cause disease at distinct body sites. In all three species, deletion of fabM abolished MUFA production and caused severe growth defects, decreased stress tolerance, increased antibiotic susceptibility, and defects in cell viability, morphology, and division. In S. mutans, loss of fabM also markedly reduced competence signaling and production of the mutacin IV bacteriocin. Deletion of fabM increased susceptibility to killing by human neutrophils in S. mutans and S. pneumoniae, but not S. pyogenes. Together, these findings illustrate that MUFA synthesis is broadly important for streptococcal physiology and cell membrane homeostasis, while its contribution to pathogenesis is strongly species- and context-dependent, providing leads to guide the development of novel therapeutic and/or preventative strategies.IMPORTANCEStreptococcus spp. exert profound effects on human health, with several species causing significant morbidity and mortality. Although streptococcal fatty acid biosynthesis and utilization are attractive metabolic targets for development of therapeutics, this opportunity is vexed by an incomplete understanding of taxon-to-taxon variability in lipid metabolism. In this study, the role of de novo monounsaturated fatty acid (MUFA) synthesis in physiology and virulence-associated traits was examined in Streptococcus mutans, Streptococcus pyogenes, and Streptococcus pneumoniae, three major pathogens that cause disease at distinct body sites. MUFA synthesis was important for stress and antibiotic tolerance across all three species, while its impact on virulence was species- and context-dependent. Overall, these discoveries provide leads to guide the development of novel therapeutic and/or preventative strategies.
– Name: Abstract
  Label: Competing Interests
  Group: Ab
  Data: The authors declare no conflict of interest.
– Name: Comment
  Label: Comments
  Group: Commnt
  Data: Update of: bioRxiv. 2026 Jan 14:2026.01.14.699484. doi: 10.64898/2026.01.14.699484.. (PMID: <searchLink fieldCode="PM" term="%2241648328%22">41648328)</searchLink>
– Name: Ref
  Label: References
  Group: RefInfo
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  Data: <i>Keywords: </i>Streptococcus; fatty acid biosynthesis
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      – SubjectFull: Cell Membrane metabolism
        Type: general
      – SubjectFull: Humans
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      – SubjectFull: Virulence
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      – SubjectFull: Streptococcus pneumoniae metabolism
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      – SubjectFull: Streptococcus pneumoniae genetics
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      – TitleFull: Monounsaturated fatty acid biosynthesis is critical for streptococcal envelope homeostasis and stress tolerance.
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              Text: 2026 Sep 17
              Type: published
              Y: 2026
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