Despite the importance of Lactobacillus iners and its unique characteristics for the study of vaginal adaption, its genome and genomic researches for identifying molecular backgrounds of these specific phenotypes are still limited. In this study, the first complete genome of L. iners was constructed using a cost-effective long-read sequencing platform, Flongle from Oxford Nanopore, and comparative genome analysis was conducted using a total of 1,046 strain genomes from 10 vaginal Lactobacillus species. Single-molecule sequencing using Flongle effectively resolved the limitation of the 2nd generation sequencing technologies in dealing with genomic regions of high GC contents, and comparative genome analysis identified three potential core genes (INY, ZnuA, and hsdR) of L. iners which was related to its specific adaption to the vaginal environment. In addition, we performed comparative prophage analysis for 1,046 strain genomes to further identify the species specificity. The number of prophages in L. iners genomes was significantly smaller than other vaginal Lactobacillus species, and one of the specific genes (hsdR) was suggested as the means for defense against bacteriophage. The first complete genome of L. iners and the three specific genes identified in this study will provide useful resources to further expand our knowledge of L. iners and its specific adaption to the vaginal econiche.

Lactobacillus iners is the most prevalent bacterial species in the human vaginal microbiome, and there have been few reports of its Gram-negative stain appearances despite the fact that the genus Lactobacillus is universally described as Gram-positive. Here, using transmission electron microscopy, we reveal that the thinness of the cell wall (17.39 ± 0.8 nm) gives the Gram-negative stain appearance, which can lead to over-diagnosis of bacterial vaginosis. Moreover, comparative genome analysis identified four genes commonly absent in L. iners genomes that might contribute to this phenotypic difference. We suggest that, along with the several niche-specific attributes identified, this unique feature may contribute to the species’ distinguished capability to thrive as the predominant species in the fluctuating vaginal environment as well.

Endometrial receptivity is a complex process that prepares the uterine endometrium for embryo implantation; insufficient endometrial receptivity is one of the causes of implantation failure. Here, we analyzed the microRNA expression profiles of exosomes derived from both receptive (RL95-2) and non-receptive (AN3-CA) endometrial epithelial cell (EEC) lines to identify exosomal miRNAs closely linked to endometrial receptivity. Among the 466 differentially expressed miRNAs, miR-205-5p was the most highly expressed in exosomes secreted from receptive RL95-2 cells. miR-205-5p, enriched at the adhesive junction, was closely related to endometrial receptivity. ZEB1, a transcriptional repressor of E-cadherin associated with endometrial receptivity, was identified as a direct target of miR-205-5p. miR-205-5p expression was significantly lower in the endometrial tissues of infertile women than in that of non-infertile women. In vivo, miR-205-5p expression was upregulated in the post-ovulatory phase, and its inhibitor reduced embryo implantation. Furthermore, administration of genetically modified exosomes overexpressing miR-205-5p mimics upregulated E-cadherin expression by targeting ZEB1 and improved spheroid attachment of non-receptive AN3-CA cells. These results suggest that the miR-205-5p/ZEB1/E-cadherin axis plays an important role in regulating endometrial receptivity. Thus, the use of exosomes harboring miR-205-5p mimics can be considered a potential therapeutic approach for improving embryo implantation.

Background: Cetuximab has shown clinical benefit in patients with metastatic colorectal cancer (mCRC) harbouring wild-type RAS. HER2 amplification has been suggested as one of the resistant mechanisms of cetuximab treatment. We evaluated association between HER2 amplification and cetuximab efficacy in mCRC patients harbouring extended RAS wild-type.

Shim SH, et al. J Gynecol Oncol. 2024 Jan;35:e66. https://doi.org/10.3802/jgo.2024.35.e66

Kim JY, et al. J Gynecol Oncol. 2023 Oct;35:e18. https://doi.org/10.3802/jgo.2024.35.e18