The chemotherapeutic options for methicillin-resistant Staphylococcus aureus (MRSA) infections are limited. Due to the multiple resistant MRSA, therapeutic failure has occurred frequently, even using antibiotics belonging to different categories in clinical scenarios, very recently. This study aimed to investigate the interactions between 11 antibiotics representing different mechanisms of action against MRSA strains and provide therapeutic strategies for clinical infections. Susceptibilities for MRSA strains were determined by broth microdilution or agar dilution according to CLSI guideline. By grouping with each other, a total of 55 combinations were evaluated. The potential synergism was detected through drug interaction assays and further investigated for time-killing curves and an in vivo neutropenic mouse infection model. A total of six combinations (vancomycin with rifampicin, vancomycin with oxacillin, levofloxacin with oxacillin, gentamycin with oxacillin, clindamycin with oxacillin, and clindamycin with levofloxacin) showed synergistic activity against the MRSA ATCC 43300 strain. However, antibacterial activity against clinical isolate #161402 was only observed when vancomycin combined with oxacillin or rifampicin in time-killing assays. Next, therapeutic effectiveness of vancomycin/oxacillin and vancomycin/rifampicin was verified by an in vivo mouse infection model inoculated with #161402. Further investigations on antimicrobial synergism of vancomycin plus oxacillin and vancomycin plus rifampicin against 113 wild-type MRSA strains were evidenced by combined antibiotic MICs and bacterial growth inhibition and in vitro dynamic killing profiles. In summary, vancomycin/rifampicin and vancomycin/oxacillin are the most potential combinations for clinical MRSA infection upon both in vitro and in vivo tests. Other synergetic combinations of levofloxacin/oxacillin, gentamycin/oxacillin, clindamycin/oxacillin, and clindamycin/fosfomycin are also selected but may need more assessment for further application.

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The extensive use of tetracycline antibiotics has led to the widespread presence of tetracycline-resistance genes in Gram-negative bacteria and this poses serious threats to human and animal health. In our previous study, we reported a method for rapid detection of Tet(X)-producers using MALDI-TOF MS. However, there have been multiple machineries involved in tetracycline resistance including efflux pump, and ribosomal protection protein. Our previous demonstrated the limitation in probing the non-Tet(X)-producing tetracycline-resistant strains. In this regard, we further developed a MALDI-TOF MS method to detect and differentiate Tet(X)-producers and non-Tet(X)-producing tetracycline-resistant strains. Test strains were incubated with tigecycline and oxytetracycline in separate tubes for 3 h and then analyzed spectral peaks of tigecycline, oxytetracycline, and their metabolite. Strains were distinguished using MS ratio for [metabolite/(metabolite+ tigecycline or oxytetracycline)]. Four control strains and 319 test strains were analyzed and the sensitivity was 98.90% and specificity was 98.34%. This was consistent with the results obtained from LC-MS/MS analysis. Interestingly, we also found that the reactive oxygen species (ROS) produced by tetracycline-susceptible strains were able to promote the degradation of oxytetracycline. Overall, the MALDI Tet(X)-plus test represents a rapid and reliable method to detect Tet(X)-producers, non-Tet(X)-producing tetracycline-resistant strains, and tetracycline-susceptible strains.

Aim. The aim of this study is to demonstrate the expression and clinicopathological significance of complement C1q B chain (C1QB) in cervical cancer. Methods. In total, 120 cervical cancer tissues, as well as 20 samples each of high-grade squamous intraepithelial lesions (HSILs), low-grade squamous intraepithelial lesions (LSILs), and benign cervical tissue, were collected to evaluate the expression of C1QB protein via immunohistochemical staining. We conducted an integrated analysis of C1QB mRNA expression in cervical cancer using public microarrays and RNA-seq data sets by calculating standard mean differences (SMDs). Simultaneously, we explored the relations of C1QB with clinicopathological parameters and the expression of P16, Ki-67, and P53. Results. The expression of C1QB protein was higher in cervical cancer samples than that in benign cervical tissue, LSIL, and HSIL samples ( p < 0.05 ). A combined SMD of 0.65 (95% CI: [0.52, 0.79], p < 0.001 ) revealed upregulation of C1QB mRNA in cervical cancer. C1QB expression may also be related to the depth of infiltration, lymphovascular invasion, and perineural invasion in cervical cancer ( p < 0.05 ). We also found that C1QB protein expression was positively correlated with P16 and Ki-67 expression in cervical cancer ( p < 0.05 ). The gene set enrichment analysis showed that C1QB may participate in apoptosis and autophagy. A relationship was predicted between C1QB expression and drug sensitivity to cisplatin, paclitaxel, and docetaxel. Conclusion. We confirmed the overexpression of C1QB in cervical cancer at both mRNA and protein levels for the first time. C1QB may serve as an oncogene in the tumorigenesis of cervical cancer, but this possibility requires further study.