Abstract

Bacterial antibiotic resistance poses a threat to global public health. Restricted usage of antibiotics does not necessarily prevent its continued emergence. Rapid and sensitive screening of triggers, in addition to antibiotic, and exploring the underlying mechanism are still major challenges. Herein, by developing a homogeneous vacuum filtration-based bacterial sample fabrication enabling high surface-enhanced Raman scattering (SERS) reproducibility across multiple bacterial samples and negating interfering spectral variations from inhomogeneous sample geometry and SERS enhancement, SERS was employed to study heavy metal arsenic [As(V)]-mediated antibiotic resistance in a robust, sensitive, and rapid fashion. Independent and robust spectral changes representing phenotypic bacterial responses, combined with multivariate analysis, clearly identified that As(V) enhanced antibiotic resistance to tetracycline (Tet). Similar spectral alteration profile to As(V) and Tet indicated that cross-resistance, whereby As(V)-induced bacterial resistance simultaneously blocked Tet action, could account for the enhanced resistance. The sensitive, robust, and rich phenotypic profile provided by SERS, combined with additional advantages in imposing no need to cultivate bacteria and single-cell sensitivity, can be further exploited to evaluate resistance-intervening factors in real microbiota.

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