Selective and suppressive effects of antibiotics on donor and recipient bacterial strains in gut microbiota determine transmission efficiency of bla_NDM-1-bearing plasmids

Objectives: To test whether antibiotics of different functional categories exhibit differential potential in promoting transmission of MDR-encoding plasmids among members of the gut microbiome. 

Methods: Rats inoculated with bla_NDM-1-bearing Klebsiella pneumoniae were subjected to treatment with different types of antibiotics. The structural changes in the gastrointestinal (GI) tract microbiome were determined by 16S rRNA sequencing and analysis. In addition, the efficiency of transmission of bla_NDM-1-bearing plasmids to different subtypes of GI tract Escherichia coli was also confirmed in vitro. 

Results: We showed that drugs that are commonly used to treat Gram-negative bacterial infections, such as ampicillin and amoxicillin, could enrich both carbapenem-resistant Enterobacteriaceae (CRE) and antibiotic-susceptible E. coli in the GI tract, thereby promoting transmission of the bla_NDM-1-bearing plasmid in the gut microbiome. In contrast, meropenemwas found to minimize the population of CRE in the gut microbiome, hence treatment with this drug exhibited drastically lower potential to promote transmission of the bla_NDM-1-bearing plasmid to the recipient strains.We further showed that an increased population size of Proteobacteria due to a suppressive effect on Firmicutes is a key factor in enhancing the efficiency of transmission of the bla_NDM-1-bearing plasmid and hence dissemination of carbapenem-resistant strains. 

Conclusions: This study depicted for the first time the effect of different antibiotics on the structure of the rat GI tract microbiome, which in turn determined the pattern and rate of transmission of the bla_NDM-1-bearing plasmid. Such findings can help establish new guidelines for prudent antibiotic usage to minimize the chance of dissemination of mobile resistance elements among members of the GI tract microbiome.