<b><i>Objectives:</i></b> The aim of this work is to evaluate the susceptibility profile of the isolates against antifungal drugs and the level of virulent genes and resistant genes mRNA expression of <i>Candida nivariensis</i>. <b><i>Methods:</i></b> We analyzed a collection of 9 <i>C. nivariensis</i> isolates from clinical isolates of <i>Candida glabrata</i> complex isolated from patients with vulvovaginal candidiasis (VVC). Antifungal susceptibilities of the isolates were assayed by using the broth microdilution method. The level of virulent genes and resistant genes mRNA expression was determined by using real-time PCR. <b><i>Results:</i></b> At day 7–14 and day 30–35 follow-up, mycological cure of VVC caused by <i>C. nivariensis</i> was 5 in 9 and 4 in 9 cases. The minimum inhibitory concentration geometric means of caspofungin, fluconazole, itraconazole, and amphotericin B in <i>C. nivariensis</i> isolates were higher than those in <i>Candida albicans</i> ATCC90028 (0.340, 1.852, 0.367, and 1.587 vs. 0.124, 0.140, 0.030, and 0.891 µg/mL; <i>p</i> < 0.05). The level of resistant genes ERG11, CDR1, and CDR2 and virulent genes YPS1, AWP3, and EPA1 mRNA expression was higher in <i>C. nivariensis</i> isolates than that of <i>C. glabrata</i> (2.58 ± 0.78, 9.31 ± 5.19, 11.10 ± 0.76, 13.57 ± 0.54, 11.96 ± 2.93, and 14.40 ± 0.61 vs. 1.05 ± 1.19, 2.22 ± 0.27, 0.85 ± 0.48, 0.30 ± 0.37, 1.90 ± 0.43, and 2.40 ± 0.65). <b><i>Conclusion:</i></b> We conclude that patients infected with <i>C. nivariensis</i> were symptomatic and with a low mycological cure rate when treated with commonly used antifungal agents. Compared with <i>C. albicans</i>, <i>C. nivariensis</i> is more antifungal resistant and virulent.
Mycoplasma genitalium protein of adhesion (MgPa) plays an important role in the process of adhesion and invasion of host cells by M. genitalium, and is thus significant for its pathogenic mechanisms in host cells. Our previous study has demonstrated that cyclophilin A (CypA) is the receptor for MgPa in human urothelial cells (SV-HUC-1) and can, therefore, mediate the adherence and invasion of M. genitalium into host cells by interacting with MgPa. However, the specific pathogenesis of M. genitalium to host cells and the possible pathogenic mechanism involved in the interaction of MgPa and CypA have never been clarified. The study aimed to elucidate the mechanism involved in the pathogenicity of MgPa. Recombinant MgPa (rMgPa) induced extracellular CypA (eCypA) was detected in SV-HUC-1 cells by ELISA, and the interaction between CypA and CD147 was validated using co-localization and co-immunoprecipitation assay. In addition, both extracellular signal-regulated kinases (ERK) phosphorylation and NF-κB activation evoked by rMgPa-induced eCypA were also demonstrated. The findings of this study verified that rMgPa could induce the secretion of eCypA in SV-HUC-1 cells and thus promote the protein and mRNA expression of IL-1β, IL-6, TNF-α and MMP-9 via CypA-CD147 interaction and thus activating ERK-NF-κB pathway, which is beneficial to elucidate the pathogenesis and possible pathogenic mechanism of M. genitalium to host cells.
Cyclophilin A (CypA), a key member of the immunophilin family, is the most abundantly expressed isozyme of the 18 known human cyclophilins. Besides acting as an intracellular receptor for cyclosporine A, CypA plays a vital role in microorganismal infections, cardiovascular diseases, liver diseases, kidney diseases, neurodegeneration, cancer, rheumatoid arthritis, periodontitis, sepsis, asthma, and aging. This review focuses on the pivotal roles of CypA in the infection of etiological agents, which manifests mainly in promoting or inhibiting viral replication based on the host cell type and viral species. CypA can interact with viral proteins and thus regulate the replication cycle of the virus. CypA is involved in pathogenic bacterial infections by regulating the formation of host actin skeleton or membrane translocation of bacterial toxins, or mediated the adhesion of Mycoplasma genitalium during the infection processes by acting as a cellular receptor of M. genitalium. CypA also plays a critical role in infection or the life cycle of certain parasites or host immune regulation. Moreover, we summarized the current understanding of CypA inhibitors acting as hosttargeting antiviral agents, thus opening an avenue for the treatment of multiple viral infections due to their broad antiviral effects and ability to effectively prevent drug resistance. Therefore, the antiviral effect of CypA has the potential to promote CypA inhibitors as host-targeting drugs to CypA-involved etiological agent infections and human diseases. Key points• CypA is involved in the replication and infection of several viruses, pathogenic bacteria, mycoplasma, and parasites.• CypA inhibitors are in a strong position to inhibit the infection of viruses, bacterial, and mycoplasma.
The polyaniline (PANI) was synthesized by chemical oxidation and was conductive media to improve the anaerobic sludge to decolorize the azo dye-containing wastewater in this study. The effect of carbon sources, chemical oxygen demand (COD) concentration and PANI dosage on the decolorization and degradation performance of anaerobic sludge was investigated. The optimized carbon source for decolorization of azo dye by anaerobic sludge was the sucrose in our research. The color removal can be increased by ~20% from the anaerobic system adding with PANI material due to the accelerated degradation of the carbon source by the PANI. Based on the decolorization, the azo dye-containing wastewater treatment could achieve an optimal effect when PANI of 400 mg/L was added in the anaerobic sludge. Finally, the effect of the additional PANI on the microorganism communities in the anaerobic sludge was also investigated.
Tuberculosis caused by Mycobacterium tuberculosis (M. tuberculosis) is the leading cause of death among infectious diseases in the worldwide. Lack of more sensitive and effective diagnostic reagents has increased the awareness of rapid diagnosis for tuberculosis. In this study, T7 phage displayed genomic DNA library of M. tuberculosis was constructed to screen the antigens that specially bind with TB-positive serum from the whole genome of M. tuberculosis and to improve the sensitivity and specificity of tuberculosis serological diagnosis. After three rounds of biopanning, results of DNA sequencing and BLAST analysis showed that 19 positive phages displayed four different proteins and the occurrence frequency of the phage which displayed ribokinase was the highest. The results of indirect ELISA and dot immunoblotting indicated that representative phages could specifically bind to tuberculosis-positive serum. The prokaryotic expression vector containing the DNA sequence of ribokinase gene was then constructed and the recombinant protein was expressed and purified to evaluate the serodiagnosis value of ribokinase. The reactivity of the recombinant ribokinase with different clinical serum was detected and the sensitivities and specificities in tuberculosis serodiagnosis were 90% and 86%, respectively by screening serum from tuberculosis patients (n = 90) and uninfected individuals (n = 90) based on ELISA. Therefore, this study demonstrated that ribokinase had good potential for the serodiagnosis of tuberculosis.
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