Zinc can counteract selection for ciprofloxacin resistance

Abstract

Antimicrobial 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.

Environmental drivers and interaction mechanisms of heavy metal and antibiotic resistome exposed to amoxicillin during aerobic composting

“…Comparatively, the concentrations of bio-Cu and bio-Zn in the AMX group were slightly higher than those in the CK group during the early stage of composting. This difference indicated that the addition of AMX likely hindered the passivation process of HMs and, thus, increased the risks of HMs contamination and the co-selection pressure of inducing bacterial resistance, which was also confirmed by previous reports ( Song et al, 2017 ; Vos et al, 2019 ).…”

“…With the overuse, misuse, and abuse of antibiotics in modern medicine and the livestock industry in the last decades ( Yao L. et al, 2020 ; Zhang et al, 2020 ; Zou et al, 2020 ; Wang et al, 2021 ), antimicrobial resistance has developed into one of the most urgent public health crises in recent years ( Zhu et al, 2017a ; Vos et al, 2019 ; Joshi and Kim, 2020 ; Dai et al, 2022 ). According to statistics, the global defined daily doses of antibiotics reached 34.8 billion in 2015 and have increased by 65% since 2000 ( Zhao R. et al, 2019 ).…”

“…These environmental pollutants (HMs, antibiotics, etc.) can release (co-)selection pressure, induce HMs resistome (MRGs) development and mobile genetic elements (including intI1 ) mediated HGT ( Imran et al, 2019 ; Zhao Y. et al, 2019 ; Lu et al, 2020 ) and accelerate the spread of bacterial resistance ( Zhao et al, 2017 ; Vos et al, 2019 ), thereby seriously threatening the environmental health ( Guo et al, 2019 ; Imran et al, 2019 ; Yang et al, 2019 ). Worse still, even HMs of low concentration has high persistence ( Yin et al, 2017 ; Vos et al, 2019 ) and strong selective pressure of antibiotic resistance in certain cases ( Imran et al, 2019 ; Zhang J. et al, 2019 ), among which Cu was shown to be the strongest ability to promote ARGs conjugate transfer ( Ji et al, 2012 ; Guo et al, 2019 ; Zhang R. et al, 2019 ).…”

Photodegradation of Ciprofloxacin-Zinc Complexes Produced at the Interface of ZnO and Cu-Doped ZnO Crystals

“…Thus, in the presence of ZnO and Cu-ZnO, the formation of Cipro-Zn chelates occurred, which are desirable species because they prevent bacterial selection for resistance 57 . In addition, CIPRO-Zn exhibited efficient photodegradation under UV light exposure.…”

Does Environmental Exposure to Pharmaceutical and Personal Care Product Residues Result in the Selection of Antimicrobial‐Resistant Microorganisms, and is this Important in Terms of Human Health Outcomes?

“…Zinc is used in numerous cosmetic products as an antioxidant, antiaging, antimicrobial, and anti-inflammatory agent (Abendrot & Kalinowska-Lis, 2018). In a single-species competition experiment, zinc increased the MSC of ciprofloxacin by fivefold, suggesting that zinc and ciprofloxacin behave antagonistically (Vos et al, 2020).…”