Abstract
ABSTRACTAntimicrobial resistance (AMR) has emerged as one of the most pressing threats to public health. AMR evolution occurs in the clinic but also in the environment, where antibiotics and heavy metals can select and co-select for AMR. While the selective potential of both antibiotics and metals is increasingly well-characterized, experimental studies exploring their combined effects on AMR evolution are rare. It has previously been demonstrated that fluoroquinolone antibiotics such as ciprofloxacin can chelate metal ions. To investigate how ciprofloxacin resistance is affected by the presence of metals, we quantified selection dynamics between a ciprofloxacin-susceptible and a ciprofloxacin-resistant Escherichia coli strain across a gradient of ciprofloxacin concentrations in presence and absence of zinc. The presence of zinc reduced growth of both strains, while ciprofloxacin inhibited exclusively the susceptible one. When present in combination zinc retained its inhibitory effect, while ciprofloxacin inhibition of the susceptible strain was reduced. Consequently, the minimal selective concentration for ciprofloxacin resistance increased up to five-fold in the presence of zinc. Environmental pollution usually comprises complex mixtures of antimicrobial agents. In addition to the usual focus on additive or synergistic interactions in complex selective mixtures, our findings highlight the importance of antagonistic selective interactions when considering resistance evolution.
Highlights
The emergence and spread of antimicrobial resistance (AMR) genes in bacterial pathogens constitutes a major threat to human health (WHO 2014)
To investigate how ciprofloxacin resistance is affected by the presence of metals, we quantified selection dynamics between a ciprofloxacin-susceptible and a ciprofloxacin-resistant Escherichia coli strain across a gradient of ciprofloxacin concentrations in presence and absence of zinc
Recent studies utilising both single species (Gullberg et al 2011, 2014; Liu et al 2011; Klumper et al 2019b) and complex microbial communities (Lundstrom et al 2016; Kraupner et al 2018; Murray et al 2018) have demonstrated that selection for Antimicrobial resistance (AMR) can occur at antibiotic concentrations much lower than those preventing the growth of susceptible bacteria
Summary
The emergence and spread of antimicrobial resistance (AMR) genes in bacterial pathogens constitutes a major threat to human health (WHO 2014). Recent studies utilising both single species (Gullberg et al 2011, 2014; Liu et al 2011; Klumper et al 2019b) and complex microbial communities (Lundstrom et al 2016; Kraupner et al 2018; Murray et al 2018) have demonstrated that selection for AMR can occur at antibiotic concentrations much lower than those preventing the growth of susceptible bacteria. These studies highlight the importance of considering the minimal selective concentration (MSC) in addition to the minimal inhibitory concentration (MIC) for assessing risks associated with antibiotic concentrations in the environment. Heavy metals such as copper (Cu) and zinc (Zn) may even constitute stronger selective agents for antibiotic resistance than antibiotics (Song et al 2017)
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