Dissolved Fe(III) defines a stabilizing window for tetracycline resistance evolution under environmentally relevant...

Area of Science:

• Environmental microbiology
• Antimicrobial resistance evolution
• Wastewater treatment

Background:

• Dissolved iron and sub-inhibitory tetracycline are common in aquatic environments and wastewater treatment.
• Understanding iron's role in tetracycline resistance evolution is crucial for managing antimicrobial resistance (AMR).

Purpose of the Study:

• To investigate how dissolved iron concentration affects tetracycline resistance evolution in Escherichia coli.
• To elucidate the mechanisms underlying iron's influence on resistance development.

Main Methods:

• Long-term serial passaging experiments with Escherichia coli MG1655 under co-exposure to Fe(III) and tetracycline.
• Short-term physiological assays and molecular analyses to assess resistance mechanisms.
• Development and application of an exposure-damage-homeostatic cost (E-D-C) framework.

Main Results:

• Resistance evolution exhibited a non-monotonic response to iron concentration, with a stabilizing window (1-4 μM Fe) minimizing evolution.
• Cellular damage was the primary driver of resistance, followed by antibiotic exposure; homeostatic cost had a minor constraining effect.
• Iron limitation favored efflux pumps, while iron overload selected for ribosomal protection or inactivation mechanisms.

Conclusions:

• Dissolved iron concentration critically modulates tetracycline resistance evolution, with a specific range offering a protective effect.
• The E-D-C framework explains resistance patterns, highlighting damage as a key factor.
• Findings underscore the environmental relevance of iron in AMR selection within aquatic systems and wastewater treatment.