Whether antibiotic resistance driven by environmental pollutant represents a transient ecological response or a permanent evolutionary shift remains a critical knowledge gap in global health. Here, we tracked the antibiotic tolerance evolution of the primary producer Synechocystis sp. PCC 6803 under chronic exposure (140 d) to environmentally relevant concentrations of copper [Cu(II): 250 μg/L] and the fluoroquinolone antibiotic moxifloxacin [MOX: 20 μg/L], respectively. The evolved cyanobacterial populations acquired high-level tolerance without obvious fitness costs. Notably, this tolerance exhibited dual characteristics: multidrug cross-tolerance was transient and fully reversible upon stressor removal, whereas tolerance to the selective agent itself [Cu(II) or MOX] was stable and heritable. Multi-omics analyses revealed the mechanistic basis for this divergence. Transient tolerance was driven by a highly dynamic form of phenotypic plasticity—manifested as transcriptional reprogramming and large-scale genomic variations that conferred a temporary fitness advantage but were rapidly lost without selective pressures. In contrast, the persistent resistance was cemented by the point mutation in rpoB gene. Our findings demonstrate that pollutants in the environment may drive the antibiotic resistance evolution in cyanobacteria and foster persistent stress tolerance. This highlights the potential risks of primary producers in the aquatic environment as an antibiotic resistance reservoir and vectors for antibiotic resistance dissemination, underscoring the necessity of integrated risk assessment and source control strategies under the “One Health” framework.
Microplastics (MPs) and antibiotics co-occur widely in the environment and pose combined risk to microbial communities. The present study investigated the effects of erythromycin on biofilm formation and resistance mutation of a model bacterium, E. coli , on the surface of pristine and UV-aged polystyrene (PS) MPs sized 1–2 mm. The properties of UV-aged PS were significantly altered compared to pristine PS, with notable increases in specific surface area, carbonyl index, hydrophilicity, and hydroxyl radical content. Importantly, the adsorption capacity of UV-aged PS towards erythromycin was approximately 8-fold higher than that of pristine PS. Biofilms colonizing on UV-aged PS had a greater cell count (5.6 × 10 8 CFU mg −1 ) and a higher frequency of resistance mutation (1.0 × 10 −7 ) than those on pristine PS (1.4 × 10 8 CFU mg −1 and 1.4 × 10 −8 , respectively). Moreover, erythromycin at 0.1 and 1.0 mg L − 1 significantly ( p < 0.05) promoted the formation and resistance mutation of biofilm on both pristine and UV-aged PS. DNA sequencing results confirmed that the biofilm resistance was attributed to point mutations in rpoB segment of the bacterial genome. qPCR results demonstrated that both UV aging and erythromycin repressed the expression levels of a global regulator rpoS in biofilm bacteria, as well as two DNA mismatch repair genes mutS and uvrD , which was likely to contribute to increased resistance mutation frequency.
Xiuyan Han,Changming Chen,Renxiang Zhao,Jing Wu,Shujing Zhang,Yuzhuo Wu,Yufang Ma,Chao Wang,Xiaochi Ma
Euphorbia fischeriana has been traditionally used in Chinese medicine for tuberculosis (TB) treatment since ancient times. In this study, we first report the identification of an abietane-type diterpenoid, 17-hydroxy-jolkinolide B (HJKB), from E. fischeriana , which exhibits potent antimycobacterial activity against both Mycobacterium tuberculosis H37Ra strain and clinical isolates. The minimum inhibitory concentrations (MICs) of HJKB against diverse M. tuberculosis strains range from 1 to 12 μg/mL. Notably, HJKB demonstrates significant bactericidal activity against intracellular M. tuberculosis H37Ra in macrophage models, accompanied by anti-inflammatory effects at concentrations of 2–5 μg/mL. Using a combination of chemoproteomic analysis and pull-down assays, we explored the preliminary antimycobacterial mechanism of HJKB. Results indicate that HJKB interacts with the target proteins RpoB and RpoC in M. tuberculosis H37Ra, a finding further corroborated by molecular docking studies. RpoB and RpoC are essential subunits of the DNA-directed RNA polymerase holoenzyme, which is critical for bacterial ribosomal transcription regulation. In summary, HJKB represents a bioactive constituent of E. fischeriana with anti-TB efficacy, acting as a transcription inhibitor against M. tuberculosis . This study not only elucidates its antimycobacterial mechanism but also provides a preclinical foundation for the development of natural product-based TB therapeutics.
危险品化学品经营许可证（带存储）