Resistance to only ertapenem is an unusual phenotype of carbapenem-resistant Klebsiella pneumoniae (CRKP). This study aimed to investigate the molecular epidemiology and underlying mechanism involved in ertapenem resistance of K. pneumoniae strains that are susceptible to meropenem and imipenem. Among the 697 K. pneumoniae strains isolated from 11 grade A hospitals in China, 245 were CRKP strains, of which 18 strains resistant only to ertapenem were isolated. The genotypes, phenotypes, drug resistance homology, and drug sensitivity were analyzed; moreover, the expressions of efflux pump components and outer membrane proteins were assessed. The whole genomes of these 18 strains were sequenced and analyzed for mutations leading to drug resistance. The results revealed that ertapenem resistance may be related to ramR mutation. The function of ramR was confirmed using gene complementation to the original strain to determine the mechanism underlying ertapenem resistance of K. pneumoniae strains. In total, 7.4% of the tested CRKP strains were resistant only to ertapenem. None of these strains contained carbapenemase genes. Of the 18 ertapenem-resistant strains, 17 expressed the efflux pump, and outer membrane protein expression was reduced or absent in 4 strains. Whole-genome sequencing revealed the presence of mutations that introduced premature ramR codons stop in 14 strains (77.78%). When a functional copy of ramR was restored in the 14 strains, the minimum inhibitory concentration of ertapenem decreased, inhibition of efflux pumps was not detected, and the expression of outer membrane protein OmpK35 was either increased or was restored. These findings reveal the existence of ertapenem-resistant K. pneumoniae exhibiting no clonal transmission between strains. Mutations in ramR were demonstrated to cause efflux pump inhibition and over-expression of outer membrane protein OmpK35 in some strains, which is implicated in ertapenem resistance only in K. pneumoniae.

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Background: Although Th17 cells and regulatory T cells play critical roles in autoimmune hepatitis, the balance between them in acute and chronic immune hepatitis is not well-studied. The objective of this study was to explore the role of Th17/Treg balance in autoimmune hepatitis. Methods: Thirty female Wistar rats were randomly divided into the following three groups: acute model (AC), chronic model (CC), and healthy control (HC). Aspartate aminotransferase, alanine aminotransferase, and bilirubin levels were measured. Peripheral blood interleukin (IL)-17, IL-6, IL-10, and transforming growth factor-β cytokine levels were also assessed. Flow cytometry was used to detect changes in the Th17 cell and Treg cell frequency, and the Th17/Treg ratio was calculated. Results: The frequency of Th17 cells and Treg cells were both increased (p < 0.05) and the Th17/Treg ratio was higher in the AC group compared with those in the HC group (p < 0.05). Th17 cell levels were significantly lower and Treg cell levels were significantly higher in the CC group, compared with those in the AC group (p < 0.05). In addition, the Th17/ Treg ratio was lower in the CC group compared with that in the HC group (p < 0.05). Conclusion:The Th17/Treg ratio was increased in the acute immune liver injury model and decreased in the chronic liver injury model. Th17/Treg imbalance may play a critical role in liver injury occurrence and development.K E Y W O R D S α-galcer, autoimmune hepatitis, ConA, Th17 cells, Treg cells Key points• Different liver damage caused by different modeling types will further explain the role of Th17/Treg imbalance in autoimmune hepatitis, and this imbalance has important implications for changes in immune status and disease progression. • In this study, α-galactosylceramide was used to establish the autoimmune hepatitis model, which shows similar pathological manifestations as that in human autoimmune hepatitis.