Pseudomonas Acts as a Reservoir of Novel Tigecycline Resistance Efflux Pump tmexC6D6-toprJ1b and tmexCD-toprJ Variants.

Several variants of the plasmid-carried tigecycline resistance gene cluster, tmexCD-toprJ, have been identified. This study characterized another novel variant, tmexC6D6-toprJ1b, located on the chromosome of environmental-origin Pseudomonas mendocina. TMexC6D6-TOprJ1 mediates resistance to multiple drugs, including tigecycline. The promoter activity of tmexC6D6-toprJ1b and negative transcriptional repression by the upstream regulator tnfxB6 are crucial for the expression of tmexC6D6-toprJ1b. tmexC6D6-toprJ1b was found in the plasmids or chromosomes of different Pseudomonas species from six countries. Two genetic backgrounds, class 1 integrons and int-carrying integrase units, were found adjacent to the tmexC6D6-toprJ1b gene cluster and might mediate the transfer of this novel efflux pump gene cluster in Pseudomonas. Further phylogenetic analysis revealed Pseudomonas as the major reservoir of tmexCD-toprJ variants, warranting closer monitoring in the future. IMPORTANCE Tigecycline is one of the treatment options for serious infections caused by multidrug-resistant bacteria, and tigecycline resistance has gained extensive attention. The emergence of a transferable tigecycline resistance efflux pump gene cluster, tmexCD-toprJ, severely challenged the efficiency of tigecycline. In this study, we identified another novel tmexCD-toprJ variant, tmexC6D6-toprJ1b, which could confer resistance to multiple classes of antibiotics, including tigecycline. Although tmexC6D6-toprJ1b was found only in Pseudomonas species, tmexC6D6-toprJ1b might spread to Enterobacteriaceae hosts via mobile genetic elements resembling those of other tmexCD-toprJ variants, compromising the therapeutic strategies. Meanwhile, novel transferable tmexCD-toprJ variants are constantly emerging and mostly exist in Pseudomonas spp., indicating Pseudomonas as the important hidden reservoir and origin of tmexCD-toprJ variants. Continuous monitoring and investigations of tmexCD-toprJ are urgent to control its spread.

High expression of ZNF93 promotes proliferation and migration of ovarian cancer cells and relates to poor prognosis.

Ovarian cancer (OC) is most common type of gynecologic cancer and is frequently lethal. It is important to determine the pathologic mechanisms underlying OC. ZNF93 is a member of the zinc finger protein family. Abnormal expression of ZNF93 has been observed in various tumor cells. However, its clinical significance and biologic function in ovarian cancer remain unclear. In the present study, we established that ZNF93 expression was highly up-regulated in OC samples and was closely correlated with clinical stage, indicating poor prognosis. We then established that ZNF93 promoted OC cell proliferation and migration. The results of our study may provide insight into the use of ZNF93 as a marker of clinical outcome and as a potential therapeutic target in OC.

Inhibition of CTHRC-1 by its specific monoclonal antibody attenuates cervical cancer cell metastasis.

Although combination of surgery and chemo-radiotherapy could cure 80-95% of patients with early cervical cancer, there is still no satisfactory therapeutic strategies for locally advanced and metastatic cervical cancer patients. Our previous study has already investigated that CTHRC-1 is highly expressed not only in the local tissue but also in circulating serum of patients with cervical cancer and played important function on metastasis of cervical cancer cells. In present study, we aimed to see whether circulating specific monoclonal antibody (mAb) to CTHRC-1could inhibit the metastasis of advanced cervical cancer. Therefore, we innovatively generated one specific and sensitive mAb against CTHRC1 and found the CTHRC1 mAb could attenuate the promoting function of rCTHRC-1 on wound healing and invasion of SiHa cell in vitro. In addition, administration of mAb on the lung metastasis mouse model of cervical cancer strongly inhibited the level of metastasis. Taken together, targeting on CTHRC-1 is greatly beneficial not only for diagnosis but also for treatment of cervical cancer, which providing experimental and theoretical basis for developing a novel precise treatment of cervical cancer and improving patient survival rate.