Zinc can counteract selection for ciprofloxacin resistance

Antimicrobial resistance (AMR) has emerged as one of the most pressing global threats to public health. AMR evolution occurs in the clinic but also in the environment, where low concentrations of antibiotics and heavy metals can respectively select and co-select for resistance. While the selective potential for AMR of both antibiotics and metals is increasingly well-characterized, studies exploring the combined effect of both types of selective agents 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 an isogenic ciprofloxacin-resistant Escherichia coli MG1655 strain across a gradient of ciprofloxacin concentrations in the presence and absence of Zinc cations (Zn2+). The minimal selective concentration (MSC) for ciprofloxacin resistance significantly increased up to 5-fold in the presence of Zn2+. No such effect on the MSC was found for gentamicin, an antibiotic not known to chelate zinc cations. Environmental pollution usually consists of complex mixtures of antimicrobial agents. Our findings highlight the importance of taking antagonistic as well as additive or synergistic interactions between different chemical compounds into account when considering their effect on bacterial resistance evolution.\n\nGraphical abstract\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=150 SRC=\"FIGDIR/small/780981v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (23K):\norg.highwire.dtl.DTLVardef@9abc9eorg.highwire.dtl.DTLVardef@d54d48org.highwire.dtl.DTLVardef@1c4df88org.highwire.dtl.DTLVardef@2f67f6_HPS_FORMAT_FIGEXP M_FIG C_FIG One sentence summaryThe minimal selective concentration for a ciprofloxacin resistant E. coli strain increases up to 5-fold in the presence of Zinc cations.