Xia Xiao,Quanmin Huan,Yanhu Huang,Yuan Liu,Ruichao Li,Xilan Xu,Zhiqiang Wang
Tigecycline (TIG) is one of the last effective options against multidrug resistance bacteria. Recently, the RND (resistance–nodulation–division) efflux pump gene cluster,tmexCD1-toprJ1, and the tetracycline-efflux pumptet(A) mutation were reported to mediate high level resistance to TIG in clinically important pathogens, weakening the efficacy of TIG. In this study, we report the potent synergistic effect of the antidiabetic drug metformin in combination with TIG againsttet(A) mutant andtmexCD1-toprJ1positiveK. pneumoniae. The fractional inhibitory concentration index (FICI) of TIG and metformin were less than 0.05 for all the tested isolates. The time–kill curve assay showed that the combination of TIG and metformin exhibited much better antimicrobial effect than TIG alone. The synergistic effect was also confirmed in vivo using a well-studiedGalleria mellonellalarvae model. Mechanistic studies demonstrated that metformin disrupted the important component of proton motive force, the electric potential (Δψ) and the function of efflux pump, thereby increasing the intracellular concentration of TIG. This finding revealed that metformin might be a possible adjuvant of TIG for combating with superbugs carrying thetet(A) mutant andtmexCD1-toprJ1genes.Keywords:tigcycline;metformin;tmexCD1-toprJ1;tet(A);synergy
Direct discharge of aquaculture wastewater may have toxic effects, due to the presence of heavy metals, antibiotics, and even resistant pathogens , but little attention has been given. Here, tanks simulating a wild ecosystem were built to study the effects of long-term exposure to duck wastewater containing oxytetracycline (OTC) and/or arsenic (As) on the growth, physiological function, and gut microbiota evolution of Xenopus tropicalis . The results showed that duck wastewater had no apparent impact on X. tropicalis , but the impact increased significantly ( P < 0.05) with exposure to OTC and/or As, especially the impact on body weight and growth rate. Biochemical indicators revealed varying degrees of oxidative stress damage, hepatotoxicity (inflammation, necrosis, and sinusoids), and collagen fibrosis of X. tropicalis in all treated groups after 72 days of exposure, which indirectly inhibited X. tropicalis growth. Moreover, 16S rDNA amplicon sequencing results showed that the gut microbiota structure and metabolic function were perturbed after chronic exposure, which might be the leading cause of growth inhibition. Interestingly, the abundance of intestinal resistance genes (RGs) increased with exposure time owing to the combined direct and indirect effects of stress factors in duck wastewater. Moreover, once the RGs were expressed, the resistance persisted for at least 24 days, especially that conferred by tet A. These results provide evidence of the toxic effects of DW containing OTC (0.1–4.0 mg/L) and/or As (0.3–3.5 µg/L) on amphibians and indicate that it is vital to limit the usage of heavy metals and antibiotics on farms to control the biotoxicity of wastewater.
Boru Gao,Mengmeng Dou,Jin Wang,Shuming Li,Dongying Wang,Lin Ci,Yao Fu
Contaminants such as antibiotics and the resulting antibiotic-resistant bacteria (ARB) and antibiotic-resistant genes (ARGs) have become a hot topic in the field of wastewater purification. In this study, a method was proposed to simultaneously remove antibiotics and reduce ARB and ARGs with C–(N) 3 defect carbon nitride-coupled persulfates (CN-C V2 /PS). The location of the C–(N) 3 defects was determined by a combination of spectroscopic techniques and electron spin resonance tests. Based on photoluminescence and electrochemical tests, and deformation charge density calculations, electron traps were generated at defect sites resulting in enhanced electron–hole separation. The mineralization rates of CN-C V2 /PS for six typical antibiotics were 11–17% and 21–28% higher than those of CN-C V2 and conventional CN , respectively. Over the same reaction time, the inactivation rates of CN-C V2 /PS for E. coli and E. faecalis screened from wastewater treatment plants were 3.6 and 2.7 log higher than that of CN-C V2 . In addition, CN-C V2 /PS showed a reduction rate of more than 2.5 log for tet A and intI 1. DFT calculation showed that due to the formation of defects, the adsorption energy between the PS and catalysts increased from –8.924 eV (CN) to –18.340 eV (CN-C V2 ). At the same time, the effective stretch of peroxide bond of PS changed from 1.505 Å to 1.519 Å. Both results indicated that the activation of PS was significantly enhanced in the presence of the modified CN-C V2 . The synergetic effect of CN-C V2 /PS is expected to remove the antibiotics, resistant bacteria and genes efficiently in future wastewater advanced treatment.
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