Identification of an extensively drug-resistant Escherichia coli clinical strain harboring mcr-1 and bla(NDM-1) in Korea
JOURNAL OF ANTIBIOTICS
Authors: Han, Sunghee; Kim, Jin Seok; Hong, Chae-Kyu; Park, Sang-Hun; Kim, Hee Soon; Yu, Jin Kyung; Park, Jungsun; Kim, Junyoung; Lee, Sang-Me; Oh, Young-Hee
The development of colistin resistance in carbapenem-resistant strains poses a serious public health problem. In this study, we collected 249 carbapenem-resistant Escherichia coli isolates from patients in Seoul in 2018, and screened all isolates for colistin resistance and for the presence of mobile colistin resistance (mcr) genes. Colistin-resistant strains were further analyzed using multilocus sequence typing, antimicrobial susceptibility testing, detection of antibiotic resistance determinants, plasmid transconjugation, and whole-genome sequencing. Three of the 249 carbapenem-resistant isolates were resistant to colistin, and mcr-1 was detected in one isolate (SECR18-0888), which belonged to sequence type 156 and was resistant to all antibiotics tested except tigecycline. The mcr-1.1 gene was located on an similar to 62 kb self-transferable IncI2 plasmid along with the bla(CTX-M-55) gene, and the bla(NDM-1), bla(TEM), qepA1, and rmtB genes were additionally detected in SECR18-0888. As an extensively drug-resistant E. coli strain producing MCR-1 and NDM-1 was identified in Korea for the first time, continued monitoring of colistin resistance in carbapenem-resistant Enterobacteriaceae should be reinforced.
Antibiotic-related gut dysbiosis induces lung immunodepression and worsens lung infection in mice
Authors: Dessein, Rodrigue; Bauduin, Marvin; Grandjean, Teddy; Le Guern, Remi; Figeac, Martin; Beury, Delphine; Faure, Karine; Faveeuw, Christelle; Guery, Benoit; Gosset, Philippe; Kipnis, Eric
Background Gut dysbiosis due to the adverse effects of antibiotics affects outcomes of lung infection. Previous murine models relied on significant depletion of both gut and lung microbiota, rendering the analysis of immune gut-lung cross-talk difficult. Here, we study the effects of antibiotic-induced gut dysbiosis without lung dysbiosis on lung immunity and the consequences on acuteP.aeruginosalung infection. Methods C57BL6 mice received 7 days oral vancomycin-colistin, followed by normal regimen or fecal microbial transplant or Fms-related tyrosine kinase 3 ligand (Flt3-Ligand) over 2 days, and then intra-nasalP.aeruginosastrain PAO1. Gut and lung microbiota were studied by next-generation sequencing, and lung infection outcomes were studied at 24 h. Effects of vancomycin-colistin on underlying immunity and bone marrow progenitors were studied in uninfected mice by flow cytometry in the lung, spleen, and bone marrow. Results Vancomycin-colistin administration induces widespread cellular immunosuppression in both the lung and spleen, decreases circulating hematopoietic cytokine Flt3-Ligand, and depresses dendritic cell bone marrow progenitors leading to worsening ofP.aeruginosalung infection outcomes (bacterial loads, lung injury, and survival). Reversal of these effects by fecal microbial transplant shows that these alterations are related to gut dysbiosis. Recombinant Flt3-Ligand reverses the effects of antibiotics on subsequent lung infection. Conclusions These results show that gut dysbiosis strongly impairs monocyte/dendritic progenitors and lung immunity, worsening outcomes ofP.aeruginosalung infection. Treatment with a fecal microbial transplant or immune stimulation by Flt3-Ligand both restore lung cellular responses to and outcomes ofP.aeruginosafollowing antibiotic-induced gut dysbiosis.