Silver
nanoparticles (AgNPs) are effective antimicrobial substances
that show promise in combatting multidrug resistance. The potential
application and release of AgNPs into the environment may neutralize
the selective advantage of antibiotic resistance. Systemic knowledge
regarding the effect of NPs on the evolution of antibiotic resistance
is lacking. Our results showed that bacteria slowly developed adaptive
tolerance to ciprofloxacin (CIP) under cyclic CIP and silver ion (Ag+) cotreatment, and no resistance/tolerance was discernible
when CIP and AgNP exposure was alternated. In contrast, rapid CIP
resistance was induced under continuous selection by treatment with
only CIP. To combat the effects of CIP and Ag+, bacteria
developed convergent evolutionary strategies with similar adaptive
mechanisms, including anaerobic respiration transitioning (to reduce
oxidative stress) and stringent response (to survive harsh environments).
Alternating AgNP exposure impeded evolutionary resistance by accelerating
B12-dependent folate and methionine cycles, which reestablished DNA
synthesis and partially offset high oxidative stress levels, in contrast
with the effect of CIP-directed evolutionary pressure. Nevertheless,
CIP/AgNP treatment was ineffective in attenuating virulence, and CIP/Ag+ exposure even induced the virulence-critical type III secretion
system. Our results increase the basic understanding of the impacts
of NPs on evolutionary biology and suggest prospective nanotechnology
applications for arresting evolutionary antibiotic resistance.
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