|
| Status |
Public on Jun 26, 2024 |
| Title |
Vaginal Lactobacillus fatty acid response mechanisms reveal a metabolite-targeted strategy for bacterial vaginosis treatment |
| Organisms |
Lactobacillus gasseri; Lactobacillus crispatus; Lactobacillus jensenii |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Bacterial vaginosis (BV), a common syndrome characterized by Lactobacillus-deficient vaginal microbiota, is associated with adverse health outcomes. BV often recurs after standard antibiotic therapy in part because antibiotics promote microbiota dominance by Lactobacillus iners instead of Lactobacillus crispatus, which has more beneficial health associations. Strategies to promote L. crispatus and inhibit L. iners are thus needed. We show that oleic acid (OA) and similar long-chain fatty acids simultaneously inhibit L. iners and enhance L. crispatus growth. These phenotypes require OA-inducible genes conserved in L. crispatus and related lactobacilli, including an oleate hydratase (ohyA) and putative fatty acid efflux pump (farE). FarE mediates OA resistance, while OhyA is robustly active in the vaginal microbiota and enhances bacterial fitness by biochemically sequestering OA in a derivative form only ohyA-harboring organisms can exploit. OA promotes L. crispatus dominance more effectively than antibiotics in an in vitro BV model, suggesting a metabolite-based treatment approach.
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| Overall design |
We hypothesized that non-iners female genital tract (FGT) Lactobacillus species’ similar uLCFA growth responses reflected a shared response mechanism. We therefore assessed L. crispatus, L. gasseri, and L. jensenii transcriptional responses to oleic acid (OA), linoleic acid (LOA), and palmitoleic acid (POA).
|
| Web link |
https://www.biorxiv.org/content/10.1101/2023.12.30.573720v1
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| |
|
| Contributor(s) |
Zhu M, Blainey P, Bloom S, Kwon D |
| Citation(s) |
38234804, 39163861 |
| |
| Submission date |
Jun 24, 2024 |
| Last update date |
Oct 10, 2024 |
| Contact name |
Douglas S Kwon |
| E-mail(s) |
[email protected]
|
| Organization name |
Ragon Institute
|
| Lab |
Kwon
|
| Street address |
600 Main ST
|
| City |
Cambridge |
| State/province |
MA |
| ZIP/Postal code |
02141 |
| Country |
USA |
| |
|
| Platforms (3) |
| GPL34634 |
Illumina NovaSeq 6000 (Lactobacillus crispatus) |
| GPL34635 |
Illumina NovaSeq 6000 (Lactobacillus gasseri) |
| GPL34636 |
Illumina NovaSeq 6000 (Lactobacillus jensenii) |
|
| Samples (36)
|
|
| Relations |
| BioProject |
PRJNA1127587 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE270628_DESeq2_results_FGT-85-Lg-1LOA_vs_Lg-1CTRL_LRT_3_3_GCF_022456925.1_ASM2245692v1_genomic_All.txt.gz |
375.0 Kb |
(ftp)(http) |
TXT |
| GSE270628_DESeq2_results_FGT-85-Lg-1OA_vs_Lg-1CTRL_LRT_3_3_GCF_022456925.1_ASM2245692v1_genomic_All.txt.gz |
371.5 Kb |
(ftp)(http) |
TXT |
| GSE270628_DESeq2_results_FGT-85-Lg-1POA_vs_Lg-1CTRL_LRT_3_3_GCF_022456925.1_ASM2245692v1_genomic_All.txt.gz |
378.5 Kb |
(ftp)(http) |
TXT |
| GSE270628_DESeq2_results_FGT-85-Lj-1LOA_vs_Lj-1CTRL_LRT_3_3_GCF_022456915.1_ASM2245691v1_genomic_All.txt.gz |
325.3 Kb |
(ftp)(http) |
TXT |
| GSE270628_DESeq2_results_FGT-85-Lj-1OA_vs_Lj-1CTRL_LRT_3_3_GCF_022456915.1_ASM2245691v1_genomic_All.txt.gz |
319.7 Kb |
(ftp)(http) |
TXT |
| GSE270628_DESeq2_results_FGT-85-Lj-1POA_vs_Lj-1CTRL_LRT_3_3_GCF_022456915.1_ASM2245691v1_genomic_All.txt.gz |
328.1 Kb |
(ftp)(http) |
TXT |
| GSE270628_DESeq2_results_FGT88B-Lc-12LOA_vs_Lc-12CTRL_LRT_3_3_GCF_022455535.1_ASM2245553v1_genomic_All.txt.gz |
265.7 Kb |
(ftp)(http) |
TXT |
| GSE270628_DESeq2_results_FGT88B-Lc-12OA_vs_Lc-12CTRL_LRT_3_3_GCF_022455535.1_ASM2245553v1_genomic_All.txt.gz |
262.0 Kb |
(ftp)(http) |
TXT |
| GSE270628_DESeq2_results_FGT88B-Lc-12POA_vs_Lc-12CTRL_LRT_3_3_GCF_022455535.1_ASM2245553v1_genomic_All.txt.gz |
258.6 Kb |
(ftp)(http) |
TXT |
| GSE270628_FGT-85_GCF_022456915.1_ASM2245691v1_genomic_all_counts.tsv.gz |
199.2 Kb |
(ftp)(http) |
TSV |
| GSE270628_FGT-85_GCF_022456925.1_ASM2245692v1_genomic_all_counts.tsv.gz |
222.0 Kb |
(ftp)(http) |
TSV |
| GSE270628_FGT88B_GCF_022455535.1_ASM2245553v1_genomic_all_counts.tsv.gz |
222.9 Kb |
(ftp)(http) |
TSV |
| GSE270628_GCF_022455535.1_ASM2245553v1_translated_cds.fasta.gz |
354.7 Kb |
(ftp)(http) |
FASTA |
| GSE270628_GCF_022456915.1_ASM2245691v1_translated_cds.fasta.gz |
348.2 Kb |
(ftp)(http) |
FASTA |
| GSE270628_GCF_022456925.1_ASM2245692v1_translated_cds.fasta.gz |
423.7 Kb |
(ftp)(http) |
FASTA |
SRA Run Selector |
| Raw data are available in SRA |
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