K. pneumoniae is one of the most frequent Gram-negative bacilli isolated from bloodstream infections worldwide and recent studies have shown an increased rate of carbapenem resistance in China. Among carbapenem-resistant K. pneumoniae (CRKP) diverse clones have been reported, especially the high-risk clone ST11, which also exhibited a multidrug resistant phenotype.

Many antimicrobial resistance genes usually located on transferable plasmids are responsible for multiple antimicrobial resistance among multidrug-resistant (MDR) Gram-negative bacteria. The aim of this study is to characterize a carbapenemase-producing Enterobacter hormaechei 1575 isolate from the blood sample in a tertiary hospital in Wuhan, Hubei Province, China. Antimicrobial susceptibility test showed that 1575 was an MDR isolate. The whole genome sequencing (WGS) and comparative genomics were used to deeply analyze the molecular information of the 1575 and to explore the location and structure of antibiotic resistance genes. The three key resistance genes (blaSFO–1, blaNDM–1, and mcr-9) were verified by PCR, and the amplicons were subsequently sequenced. Moreover, the conjugation assay was also performed to determine the transferability of those resistance genes. Plasmid files were determined by the S1 nuclease pulsed-field gel electrophoresis (S1-PFGE). WGS revealed that p1575-1 plasmid was a conjugative plasmid that possessed the rare coexistence of blaSFO–1, blaNDM–1, and mcr-9 genes and complete conjugative systems. And p1575-1 belonged to the plasmid incompatibility group IncHI2 and multilocus sequence typing ST102. Meanwhile, the pMLST type of p1575-1 was IncHI2-ST1. Conjugation assay proved that the MDR p1575-1 plasmid could be transferred to other recipients. S1-PFGE confirmed the location of plasmid with molecular weight of 342,447 bp. All these three resistant genes were flanked by various mobile elements, indicating that the blaSFO–1, blaNDM–1, and mcr-9 could be transferred not only by the p1575-1 plasmid but also by these mobile elements. Taken together, we report for the first time the coexistence of blaSFO–1, blaNDM–1, and mcr-9 on a transferable plasmid in a MDR clinical isolate E. hormaechei, which indicates the possibility of horizontal transfer of antibiotic resistance genes.

Introduction Vancomycin, teicoplanin, linezolid and daptomycin are four major antibacterials used for methicillin-resistant Staphylococcus aureus (MRSA) infection treatment. However, with the increasing failure of clinical MRSA anti-infective treatment, it is urgent to investigate the status of MRSA sensitivity to these four drugs. Methods In the present study, 407 non-duplicated MRSA isolates from 6 provinces in China were collected from January 2018 to August 2020. The minimum inhibitory concentrations (MICs) of vancomycin, teicoplanin, linezolid and daptomycin were determined by broth microdilution method, and their MIC50, MIC90, and geometric mean MIC were calculated. Results All 407 MRSA strains were sensitive to these four antibacterials. MIC range of vancomycin, teicoplanin, linezolid and daptomycin was 0.25 to 2 mg/L, 0.125 to 4 mg/L, 0.25 to 4 mg/L and 0.06 to 1 mg/L, respectively. Between 2018 and 2020, there was no “MIC creep” in vancomycin, teicoplanin and daptomycin. The geometric mean MIC of linezolid was not increased, but both MIC50 and MIC90 in 2019 and 2020 MRSA isolates were higher than 2018 isolates. Conclusion All MRSA isolates remained sensitivity to vancomycin, teicoplanin, linezolid and daptomycin. The linezolid MIC50 and MIC90 increased have been found in this study.

Asiaticoside (AS) has been reported to have protective effect on pulmonary fibrosis (PF). In this study, we aimed to explore the potential mechanism of the therapeutic role of AS and its relationship with A2AR in PF. Adenosine 2A receptor gene knockout (A2AR −/− ) mice and wild‐type (WT) mice were used to establish bleomycin (BLM)‐induced PF models and were then treated with AS (50 mg/kg/d). Pulmonary inflammation and fibrosis were observed in the PF model with much higher severity in A2AR −/− mice than that in WT mice and AS significantly alleviated lung inflammation and fibrosis; however, it was less effective in A2AR −/− mice than in WT mice via histopathological analysis. Using RNA sequencing analysis, we found up‐regulated differentially expressed genes (DEGs) in BLM group were enriched in immune and inflammation‐associated pathways compared with control group. There were 242 common DEGs between down‐regulated in BLM vs control group and up‐regulated in BLM + AS vs BLM group, which were enriched in cAMP and Rap1 signalling pathways. Furthermore, the expression of five key factors of these two pathways including adenylate cyclase ( ADCY1 , ADCY5 , ADCY8 , cAMP and Rap1) were confirmed up‐regulated by AS with the presence of A2AR. Therefore, AS might attenuate BLM‐induced PF by activating cAMP and Rap1 signalling pathways which is assisted by A2AR, making it a promising therapeutic optional for PF.

Introduction: The ability of Staphylococcus aureus to form biofilms is associated with high mortality and treatment costs. Established biofilms cannot be eradicated by many conventional antibiotics due to the development of antibiotic tolerance by S. aureus. Here we report the synthesis and biological characterization of novel small-molecule compounds with antibiofilm activity. Chromone 5-maleimide substitution compounds (CM3a) showed favorable antibacterial activity against S. aureus. Methods: CM3A with antibacterial activity was synthesized and screened. The minimum inhibitory concentration (MIC) of CM3a were determined by the broth microdilution method. Biofilm eradication assay and colony count methods were used to investigate the effect of CM3a on S. aureus biofilm disruption and killing. Changes in biofilm architecture when subjected to CM3a, were visualized using confocal laser scanning microscopy (CLSM). CCK-8 assay and survival rate of Galleria mellonella larvae were used to test the toxicity of CM3a. Results: The minimum inhibitory concentration (MIC) of CM3a against S. aureus was about 26.4 μM. Biofilm staining and laser scanning confocal microscopy analysis showed that CM3a eradicated S. aureus biofilms by reducing the viability of the constituent bacterial cells. On the other hand, CM3a showed negligible toxicity against mouse alveolar epithelial cells and Galleria mellonella larvae. Conclusion: Chromone derivatives CM3a has therapeutic potential as a safe and effective compound for the treatment of S. aureus infection.