Antibiotic resistance and pathogenicity assessment of various Gardnerella sp. strains in local China.

Gardnerella overgrowth is the primary cause of bacterial vaginosis (BV), a common vaginal infection with incidences as high as 23-29% worldwide. Here, we studied the pathogenicity, drug resistance, and prevalence of varying Gardnerella spp. We isolated 20 Gardnerella strains from vaginal samples of 31 women in local China. Ten strains were then selected via phylogenetic analysis of cpn60 and vly gene sequences to carry out genome sequencing and comparative genomic analysis. Biofilm-formation, sialidase, and antibiotic resistance activities of the strains were characterized. All strains showed striking heterogeneity in genomic structure, biofilm formation and drug resistance. Two of the ten strains, JNFY3 and JNFY15, were classified as Gardnerella swidsinskii and Gardnerella piotii, respectively, according to their phenotypic characteristics and genome sequences. In particular, seven out of the ten strains exhibited super resistance (≥ 128 µg/mL) to metronidazole, which is the first line of treatment for BV in China. Based on the biochemical and genomic results of the strains, we proposed a treatment protocol of prevalent Gardnerella strains in local China, which provides the basis for accurate diagnosis and therapy.

OLFM4 Inhibits Epithelial-Mesenchymal Transition and Metastatic Potential of Cervical Cancer Cells.

OLFM4 has been shown to play an important role in tumor initiation and progression. This study aims to investigate the role of OLFM4 in metastatic cervical cancer and its underlying mechanism. Here we discover that OLFM4 expression is significantly reduced in metastatic cervical cancer. Accordingly, overexpression of OLFM4 inhibits epithelial-mesenchymal transition (EMT), migration, and invasion in human cervical cancer cells. To further explore its molecular mechanisms, we reveal that OLFM4 augmentation interferes with mTOR signaling pathway, and the suppressive effects of OLFM4 on cell migration and invasion are largely weakened by phosphatidic acid (PA)-induced mTOR signal activation, which implicates the potential role of the mTOR pathway in OLFM4-related cervical metastasis. In conclusion, our results confirm OLFM4 as a tumor suppressor that inhibits cervical cancer metastasis by regulating mTOR signal pathway.

Lysyl oxidase genetic variants affect gene expression in cervical cancer.

Lysyl oxidase (LOX) is a copper-dependent amine oxidase that plays important roles in the homeostasis of tumors. The aim of this study was to investigate the association between LOX polymorphisms and cervical cancer, and the effect of these polymorphisms on gene expression. We evaluated two polymorphisms of LOX, rs1800449G/A (G473A) and rs2278226C/G, in 262 cervical cancer cases and 298 healthy controls in the Chinese population. Results showed that the prevalence of rs1800449AA genotype was significantly increased in cases than in controls (p=0.004). Individuals who carried the rs1800449A allele had a 1.56-fold increased risk for cervical cancer than those with the rs1800449G allele (p=0.003). The rs2278226CG genotype also revealed a significantly higher proportion in cases (20.6%) than in controls (7.7%, p<0.001). Interestingly, when analyzing these two polymorphisms with the serum level of LOX, we identified that cervical cancer patients carrying the rs2278226CG genotype had a significantly elevated level of LOX than those with rs2278226CC wild type, whereas the same phenomenon was not observed in controls. The rs1800449 polymorphism did not affect the LOX serum level in either controls or patients. These results suggest that the polymorphisms in the LOX gene may be involved in the development of cervical cancer through various mechanisms.