UhpTE350Q mutation along with the presence of fosA6/5 genes in the genome probably contributes to inherent fosfomycin resistance of Klebsiella pneumoniae / 南方医科大学学报

OBJECTIVE@#To investigate the molecular mechanism underlying inherent fosfomycin resistance of Klebsiella pneumoniae (K. pneumoniae).@*METHODS@#The draft genomic sequences of 14 clinical hypervirulent/hypermucoviscous K. pneumoniae (HvKP/ HmKP) isolates were obtained using the next-generation sequencing technology. The genomic sequences were analyzed using the Resistance Gene Identifier (RGI) software for predicting the resistome based on homology and SNP models in the Comprehensive Antibiotic Resistance Database (CARD) and for identification of the presence of phosphomycin resistancerelated genes uhpt and fosA and their mutations in the bacterial genomes. The results were verified by analyzing a total of 521 full-length genomic sequences of K. pneumonia strains obtained from GenBank.@*RESULTS@#All the 14 clinical isolates of HvKP/ HmKP carried hexose phosphate transporter (UhpT) gene mutation, in which the glutamic acid was mutated to glutamine at 350aa (UhpTE350Q mutation); the presence of fosA6 gene was detected in 12 (85.71%) of the isolates and fosA5 gene was detected in the other 2 (14.29%) isolates. Analysis of the genomic sequences of 521 K. pneumonia strains from GenBank showed that 508 (97.50%) strains carried UhpTE350Q mutation, 439 (84.26%) strains harbored fosA6, and 80 (15.36%) strains harbored fosA5; 507 (97.31%) strains were found to have both UhpTE350Q mutation and fosA6/5 genes in the genome. Only 12 (2.30%) strains carried fosA6/5 genes without UhpTE350Q mutation; 1 (0.19%) strain had only UhpTE350Q mutation without fosA6/5 genes, and another strain contained neither UhpTE350Q mutation nor fosA6/5 genes.@*CONCLUSION@#UhpTE350Q mutation with the presence of fosA6/5 genes are ubiquitous in K. pneumonia genomes, indicating a possible intrinsic mechanism of fosfomycin resistance in the bacterium to limit the use of fosfomycin against infections caused by K. pneumoniae, especially the multi-resistant HvKP/HmKP strains.

Research progress in therapeutic resistance mechanism and therapeutic strategy of cancer stem cells / 国际生物医学工程杂志

Cancer stem cells (CSCs) are a class of cells with self-renewal, differentiation, and tumorigenic potential in tumors. It is currently believed that the resistance of CSCs to chemotherapy and radiotherapy is an important cause of tumor recurrence and metastasis. Researchers have found that related factors in many signaling pathways endow CSCs with the ability to adapt to changes in the microenvironment, including inflammatory factors, hypoxia, low pH, and a lack of nutrients. In recent years, the mechanism of CSCs' resistance to therapy has been studied, mainly including the drug efflux mediated by the ATP-binding cassette transporter, the effect of aldehyde dehydrogenase 1 (ALDH1) activity on tumor stem cells, the enhancement of DNA damage repair and degradation of reactive oxygen species, autophagy, activation of development-related pathways, stimulation of the microenvironment, and EMT. The targeting strategies for CSCs include targeting signaling pathway inhibitors, targeting multidrug resistance, DNA damage repair, ALDH, targeting the tumor microenvironment, immunotherapy, etc. In this review, the research progress in CSCs treatment resistance and related treatment strategies was reviewed.

Current status and progress of the treatment of acute promyelocytic leukemia / 白血病·淋巴瘤

Acute promyelocytic leukemia (APL) is a special type of acute leukemia. The cure rate of APL has been significantly improved in the past decades due to the use of anthracyclines, all-trans retinoic acid and arsenic. Modern stratified treatment of APL further enhances the therapeutic efficacy and reduces the treatment-related toxicity. This article reviews the history of all-trans retinoic acid and arsenic into clinical application, and the characteristics of disease, treatment status of all-trans retinoic acid and arsenic, treatment mechanism and drug resistance mechanism in APL are introduced.

Current status and progress of the treatment of acute promyelocytic leukemia / 白血病·淋巴瘤

Acute promyelocytic leukemia (APL) is a special type of acute leukemia. The cure rate of APL has been significantly improved in the past decades due to the use of anthracyclines, all-trans retinoic acid and arsenic. Modern stratified treatment of APL further enhances the therapeutic efficacy and reduces the treatment-related toxicity. This article reviews the history of all-trans retinoic acid and arsenic into clinical application, and the characteristics of disease, treatment status of all-trans retinoic acid and arsenic, treatment mechanism and drug resistance mechanism in APL are introduced.