The effect of aminoglycosides on horizontal gene transfer in Klebsiella pneumoniae

Abstract

Antibiotic-resistant bacteria represent a global risk to public health. Horizontal gene transfer, a common mechanism for genetic exchange in bacteria, plays an essential role in the acquisition of resistance genes. In this work, we evaluated the effect of sub-lethal concentrations of antibiotics on plasmid transfer by conjugation and transformation in the opportunistic pathogen Klebsiella pneumoniae. Despite not being naturally competent, this bacterium could acquire extracellular DNA from various plasmids at a very low frequency, which increased upon incubating cells with the aminoglycoside antibiotics amikacin and gentamicin. Transfer by conjugation analyzed using a clinical isolate carrying plasmid pNDM-1 also increased in the presence of sub-lethal concentrations of antibiotics. An RNAseq analysis showed differential expression of several genes when cells were incubated in the presence of sub-lethal concentrations of amikacin suggesting metabolic and regulatory changes, as well as alteration of cell envelope components that could affect the uptake of foreign DNA. These results suggest that sub-lethal concentrations of some aminoglycosides, in particular amikacin, can promote the transfer of resistance-bearing genetic elements in K. pneumoniae, which is relevant for understanding the spread of resistance determinants in this human pathogen.

Examining the impact of zinc on horizontal gene transfer in Enterobacterales

“…While ampicillin decreased the conjugation frequencies for S. Infantis and S. London, rifampicin increased frequencies for these strains, although not significantly. Previous studies have shown that sub-inhibitory or sublethal selective pressure by antibiotics such as ciprofloxacin and amikacin can increase conjugation frequencies 8,11 . A possible explanation for these observations was given by Beaber et al 9 .…”

“…Although the effects of antimicrobials and heavy metals on bacterial conjugation are not fully understood, links between antimicrobial and heavy metal use with AMR transfer pose a high risk in settings where their use is common, such as in primary production. Inappropriate excessive use of antimicrobials and heavy metals could promote AMR transfer, thus contributing to the development of multidrug resistant pathogens, which limits treatment options, increases the associated economic burden of treatment costs, and is potentially a hazard to public health 8 .…”

Maximum levels of cross‐contamination for 24 antimicrobial active substances in non‐target feed. Part 2: Aminoglycosides/aminocyclitols: apramycin, paromomycin, neomycin and spectinomycin

“…• Exposure to sublethal levels of spectinomycin (0.5 lg/mL) increased the rate of HGT in Klebsiella pneumoniae (Acosta et al, 2020).…”

“… Exposure to sublethal levels of spectinomycin (0.5 μg/mL) increased the rate of HGT in Klebsiella pneumoniae (Acosta et al., 2020). Sub‐MIC exposure to neomycin, paromomycin, as well as amikacin, gentamicin, kanamycin and netilmicin reduced biofilms of Pseudomonas aeruginosa and also had an attenuating effect on quorum sensing‐mediated virulence (Khan et al.…”

Interplay Between Antimicrobial Resistance and Global Environmental Change

“…Even though antibiotic concentrations in most soil and water habitats fall below reported MICs for bacteria in the laboratory, they still affect bacterial physiology. There are few studies on the effect of low concentrations of antibiotics on natural communities, but studies using pure cultures in the laboratory show that sub-MICs lead to extensive changes in transcription (55,100,114,153), induce changes in the genome, and promote antibiotic resistance (31,59) and gene transfer events (1,71,92). In natural settings, low antibiotic concentrations also change transcription profiles and responses that can alter community ecology and function.…”