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81300.9171Fighting against evolution of antibiotic resistance by utilizing evolvable antimicrobial drugs. Antibiotic resistance is a worldwide public health problem (Bush et al. in Nat Rev Microbiol 9:894-896, 2011). The lack of effective therapies against resistant bacteria globally leads to prolonged treatments, increased mortality, and inflating health care costs (Oz et al. in Mol Biol Evol 31:2387-2401, 2014; Martinez in Science 321:365-367, 2008; Lipsitch et al. in Proc Natl Acad Sci USA 97:1938-1943, 2000; Taubes in Science 321:356-361, 2008; Laxminarayan et al. in Lancet, 2016; Laxminarayan et al. in Lancet Infect Dis 13:1057-1098, 2013). Current efforts towards a solution of this problem can be boiled down to two main strategies: (1) developing of new antimicrobial agents and (2) searching for smart strategies that can restore or preserve the efficacy of existing antimicrobial agents. In this short review article, we discuss the need for evolvable antimicrobial agents, focusing on a new antimicrobial technology that utilizes peptide-conjugated phosphorodiamidate morpholino oligomers to inhibit the growth of pathogenic bacteria by targeting bacterial genes.201728497241
349710.9167Biomarkers of antibiotic resistance genes during seasonal changes in wastewater treatment systems. To evaluate the seasonal distribution of antibiotic resistance genes (ARGs) and explore the reason for their patterns in different seasons and different systems, two wastewater treatment systems were selected and analyzed using high-throughput qPCR. Linear discriminant analysis (LDA) effect size (LEfSe) was used to discover the differential ARGs (biomarkers) and estimate the biomarkers' effect size. We found that the total absolute abundances of ARGs in inflows and excess sludge samples had no obvious seasonal fluctuations, while those in winter outflow samples decreased in comparison with the inflow samples. Eleven differentially abundant ARGs (biomarker genes, BmGs) (aadA5-02, aac-6-II, cmlA1-01, cmlA1-02, blaOXA10-02, aadA-02, tetX, aadA1, ereA, qacEΔ1-01, and blaTEM) in summer samples and 10 BmGs (tet-32, tetA-02, aacC2, vanC-03, aac-6-I1, tetE, ermB, mefA, tnpA - 07, and sul2) in winter samples were validated. According to 16S rRNA gene sequencing, the relative abundance of bacteria at the phylum level exhibited significant seasonal changes in outflow water (OW), and biomarker bacteria (BmB) were discovered at the family (or genus) level. Synechococcus and vadinCA02 are BmB in summer, and Trichococcus, Lactococcus, Pelosinus, Janthinobacterium, Nitrosomonadaceae and Sterolibacterium are BmB in winter. In addition, BmB have good correlations with BmGs in the same season, which indicates that bacterial community changes drive different distributions of ARGs during seasonal changes and that LEfSe is an acute and effective method for finding significantly different ARGs and bacteria between two or more classes. In conclusion, this study demonstrated the seasonal changes of BmGs and BmB at two wastewater treatment systems.201829169020
81420.9150Drown Them in Their Own Garbage: a New Strategy To Reverse Polymyxin Resistance? Purcell and colleagues offer new insights into a major mechanism of polymyxin resistance in Gram-negative bacteria (A. B. Purcell, B. J. Voss, and M. S. Trent, J Bacteriol 204:e00498-21, 2022, https://doi.org/10.1128/JB.00498-21). Inactivating a single lipid recycling enzyme causes accumulation of waste lipid by-products that inhibit a key factor responsible for polymyxin resistance.202234843378
843730.9137Tocopherol polyethylene glycol succinate-modified hollow silver nanoparticles for combating bacteria-resistance. Multiple drug resistance and the increase in the appearance of superbugs together with the exceedingly scant development of new potent antibiotic drugs pose an urgent global medical threat and imminent public security crisis. In the present study, we fabricated well-dispersed tocopherol polyethylene glycol succinate (TPGS)-capped silver nanoparticles (AgNPs) of about 10 nm in size. The hollow structure of the TPGS-capped AgNPs (TPGS/AgNPs) was confirmed and applied to load antibiotics. The TPGS/AgNPs proved to be able to cross the bacterial cell wall and penetrate into bacteria, thereby delivering more of the antibiotic to the interior of bacteria and thus enhancing the in vitro antibacterial effect of the antibiotic, even overcoming the drug-resistance in drug-resistant E. coli and Acinetobacter baumannii. It was found that the TPGS modification in the TPGS/AgNPs could decrease the activity of the efflux pumps AdeABC and AdeIJK in drug-resistant Acinetobacter baumannii via inhibiting the efflux pump genes adeB and adeJ, thus increasing the accumulation of the delivered antibiotic and overcoming the drug-resistance. Tigecycline delivered by TPGS/AgNPs could effectively antagonize drug-resistance in an acute peritonitis model mice, thereby increasing the survival rate and alleviating the inflammatory response. TPGS/AgNPs were developed as a novel and effective antibiotic delivery system and TPGS was demonstrated to have great potential as a pharmaceutical excipient for use in drug-resistant infection therapy.201930968093
81040.9135Draft genome sequencing and functional annotation and characterization of biofilm-producing bacterium Bacillus novalis PD1 isolated from rhizospheric soil. Biofilm forming bacterium Bacillus novalis PD1 was isolated from the rhizospheric soil of a paddy field. B. novalis PD1 is a Gram-positive, facultatively anaerobic, motile, slightly curved, round-ended, and spore-forming bacteria. The isolate B. novalis PD1 shares 98.45% similarity with B. novalis KB27B. B. vireti LMG21834 and B. drentensis NBRC 102,427 are the closest phylogenetic neighbours for B. novalis PD1. The draft genome RAST annotation showed a linear chromosome with 4,569,088 bp, encoding 6139 coding sequences, 70 transfer RNA (tRNA), and 11 ribosomal RNA (rRNA) genes. The genomic annotation of biofilm forming B. novalis PD1(> 3.6@OD(595nm)) showed the presence of exopolysaccharide-forming genes (ALG, PSL, and PEL) as well as other biofilm-related genes (comER, Spo0A, codY, sinR, TasA, sipW, degS, and degU). Antibiotic inactivation gene clusters (ANT (6)-I, APH (3')-I, CatA15/A16 family), efflux pumps conferring antibiotic resistance genes (BceA, BceB, MdtABC-OMF, MdtABC-TolC, and MexCD-OprJ), and secondary metabolites linked to phenazine, terpene, and beta lactone gene clusters are part of the genome.202134537868
999850.9131mSphere of Influence: Uncovering New Ways To Control Multidrug Resistance by Dissecting Essential Cell Processes. Ana L. Flores-Mireles works in the fields of microbial pathogenesis and development of new therapeutics. In this mSphere of Influence article, she reflects on how the papers "Bacterial cell wall biogenesis is mediated by SEDS and PBP polymerase families functioning semi-autonomously" by H. Cho et al. (Nat Microbiol 1:16172, 2016, https://doi.org/10.1038/nmicrobiol.2016.172) and "A comprehensive, CRISPR-based functional analysis of essential genes in bacteria" by J. M. Peters et al. (Cell 165:1493-1506, 2016, https://doi.org/10.1016/j.cell.2016.05.003) made an impact on her approach to dissecting essential processes to understand microbial pathogenesis in catheter-associated urinary tract infections and generate an effective treatment with reduced likelihood of developing resistance.201931554727
774360.9126Integrated meta-omics study on rapid tylosin removal mechanism and dynamics of antibiotic resistance genes during aerobic thermophilic fermentation of tylosin mycelial dregs. For efficient treatment of tylosin mycelial dregs (TMDs), rapid tylosin removal mechanism and dynamics of ARGs during TMDs fermentation were investigated using integrated meta-omics (genomics, metaproteomics and metabolomics) and qPCR approaches. The results showed that over 86% of tylosin was degraded on day 7 regardless of the type of bulking agents. The rapid removal of tylosin was mainly attributed to de-mycarose reaction (GH3) and esterase hydrolysis (C7MYQ7) of Saccharomonospora, and catalase-peroxidase oxidation of Bacillus (A0A077JB13). In addition, the moisture content and mobile genetic elements were vital to control the rebound of ARGs. The removal efficiency of antibiotic resistant bacteria (Streptomyces, Pseudomonas, norank_f__Sphingobacteriaceae, and Paenalcaligenes) and Intl1 (98.8%) in fermentation treatment TC21 with corncob as the bulking agent was significantly higher than that in other three treatments (88.3%). Thus, appropriate bulking agents could constrain the abundance of antibiotic resistant bacteria and Intl1, which is crucial to effectively reduce the resistance.202235307520
976270.9126AcrAB-TolC, a major efflux pump in Gram negative bacteria: toward understanding its operation mechanism. Antibiotic resistance (AR) is a silent pandemic that kills millions worldwide. Although the development of new therapeutic agents against antibiotic resistance is in urgent demand, this has presented a great challenge, especially for Gram-negative bacteria that have inherent drug-resistance mediated by impermeable outer membranes and multidrug efflux pumps that actively extrude various drugs from the bacteria. For the last two decades, multidrug efflux pumps, including AcrAB-TolC, the most clinically important efflux pump in Gram-negative bacteria, have drawn great attention as strategic targets for re-sensitizing bacteria to the existing antibiotics. This article aims to provide a concise overview of the AcrAB-TolC operational mechanism, reviewing its architecture and substrate specificity, as well as the recent development of AcrAB-TolC inhibitors. [BMB Reports 2023; 56(6): 326-334].202337254571
537980.9125Membrane-Targeting Triphenylphosphonium Functionalized Ciprofloxacin for Methicillin-Resistant Staphylococcus aureus (MRSA). Multidrug-resistant (MDR) bacteria have become a severe problem for public health. Developing new antibiotics for MDR bacteria is difficult, from inception to the clinically approved stage. Here, we have used a new approach, modification of an antibiotic, ciprofloxacin (CFX), with triphenylphosphonium (TPP, PPh(3)) moiety via ester- (CFX-ester-PPh(3)) and amide-coupling (CFX-amide-PPh(3)) to target bacterial membranes. In this study, we have evaluated the antibacterial activities of CFX and its derivatives against 16 species of bacteria, including MDR bacteria, using minimum inhibitory concentration (MIC) assay, morphological monitoring, and expression of resistance-related genes. TPP-conjugated CFX, CFX-ester-PPh(3), and CFX-amide-PPh(3) showed significantly improved antibacterial activity against Gram-positive bacteria, Staphylococcus aureus, including MDR S. aureus (methicillin-resistant S. aureus (MRSA)) strains. The MRSA ST5 5016 strain showed high antibacterial activity, with MIC values of 11.12 µg/mL for CFX-ester-PPh(3) and 2.78 µg/mL for CFX-amide-PPh(3). The CFX derivatives inhibited biofilm formation in MRSA by more than 74.9% of CFX-amide-PPh(3). In the sub-MIC, CFX derivatives induced significant morphological changes in MRSA, including irregular deformation and membrane disruption, accompanied by a decrease in the level of resistance-related gene expression. With these promising results, this method is very likely to combat MDR bacteria through a simple TPP moiety modification of known antibiotics, which can be readily prepared at clinical sites.202033143023
52290.9124Detoxification of ars genotypes by arsenite-oxidizing bacteria through arsenic biotransformation. The detoxification process of transforming arsenite (As(III)) to arsenate (As(V)) through bacterial oxidation presents a potent approach for bioremediation of arsenic-polluted soils in abandoned mines. In this study, twelve indigenous arsenic-oxidizing bacteria (AOB) were isolated from arsenic-contaminated soils. Among these, Paenibacillus xylanexedens EBC-SK As2 (MF928871) and Ochrobactrum anthropi EBC-SK As11 (MF928880) were identified as the most effective arsenic-oxidizing isolates. Evaluations for bacterial arsenic resistance demonstrated that P. xylanexedens EBC-SK As2 (MF928871) could resist As(III) up to 40 mM, while O. anthropi EBC-SK As11 (MF928880) could resist As(III) up to 25 mM. From these bacterial strains, genotypes of arsenic resistance system (ars) were detected, encompassing ars leader genes (arsR and arsD), membrane genes (arsB and arsJ), and aox genes known to be crucial for arsenic detoxification. These ars genotypes in the isolated AOBs might play an instrumental role in arsenic-contaminated soils with potential to reduce arsenic contamination.202439382695
9025100.9123BING, a novel antimicrobial peptide isolated from Japanese medaka plasma, targets bacterial envelope stress response by suppressing cpxR expression. Antimicrobial peptides (AMPs) have emerged as a promising alternative to small molecule antibiotics. Although AMPs have previously been isolated in many organisms, efforts on the systematic identification of AMPs in fish have been lagging. Here, we collected peptides from the plasma of medaka (Oryzias latipes) fish. By using mass spectrometry, 6399 unique sequences were identified from the isolated peptides, among which 430 peptides were bioinformatically predicted to be potential AMPs. One of them, a thermostable 13-residue peptide named BING, shows a broad-spectrum toxicity against pathogenic bacteria including drug-resistant strains, at concentrations that presented relatively low toxicity to mammalian cell lines and medaka. Proteomic analysis indicated that BING treatment induced a deregulation of periplasmic peptidyl-prolyl isomerases in gram-negative bacteria. We observed that BING reduced the RNA level of cpxR, an upstream regulator of envelope stress responses. cpxR is known to play a crucial role in the development of antimicrobial resistance, including the regulation of genes involved in drug efflux. BING downregulated the expression of efflux pump components mexB, mexY and oprM in P. aeruginosa and significantly synergised the toxicity of antibiotics towards these bacteria. In addition, exposure to sublethal doses of BING delayed the development of antibiotic resistance. To our knowledge, BING is the first AMP shown to suppress cpxR expression in Gram-negative bacteria. This discovery highlights the cpxR pathway as a potential antimicrobial target.202134108601
6009110.9122Efflux pump inhibitor chlorpromazine effectively increases the susceptibility of Escherichia coli to antimicrobial peptide Brevinin-2CE. Aim: The response of E. coli ATCC8739 to Brevinin-2CE (B2CE) was evaluated as a strategy to prevent the development of antimicrobial peptide (AMP)-resistant bacteria. Methods: Gene expression levels were detected by transcriptome sequencing and RT-PCR. Target genes were knocked out using CRISPR-Cas9. MIC was measured to evaluate strain resistance. Results: Expression of acrZ and sugE were increased with B2CE stimulation. ATCC8739ΔacrZ and ATCC8739ΔsugE showed twofold and fourfold increased sensitivity, respectively. The survival rate of ATCC8739 was reduced in the presence of B2CE/chlorpromazine (CPZ). Combinations of other AMPs with CPZ also showed antibacterial effects. Conclusion: The results indicate that combinations of AMPs/efflux pump inhibitors (EPIs) may be a potential approach to combat resistant bacteria.202438683168
3751120.9121Emerging mechanisms of antimicrobial resistance in bacteria and fungi: advances in the era of genomics. Bacteria and fungi continue to develop new ways to adapt and survive the lethal or biostatic effects of antimicrobials through myriad mechanisms. Novel antibiotic resistance genes such as lsa(C), erm(44), VCC-1, mcr-1, mcr-2, mcr-3, mcr-4, bla (KLUC-3) and bla (KLUC-4) were discovered through comparative genomics and further functional studies. As well, mutations in genes that hitherto were unknown to confer resistance to antimicrobials, such as trm, PP2C, rpsJ, HSC82, FKS2 and Rv2887, were shown by genomics and transcomplementation assays to mediate antimicrobial resistance in Acinetobacter baumannii, Staphylococcus aureus, Enterococcus faecium, Saccharomyces cerevisae, Candida glabrata and Mycobacterium tuberculosis, respectively. Thus, genomics, transcriptomics and metagenomics, coupled with functional studies are the future of antimicrobial resistance research and novel drug discovery or design.201829319341
6359130.9120Drug resistance of oral bacteria to new antibacterial dental monomer dimethylaminohexadecyl methacrylate. Only two reports exist on drug-resistance of quaternary ammonium monomers against oral bacteria; both studies tested planktonic bacteria for 10 passages, and neither study tested biofilms or resins. The objectives of this study were to investigate the drug-resistance of Streptococcus mutans, Streptococcus sanguinis and Streptococcus gordonii against dimethylaminohexadecyl methacrylate (DMAHDM), and to evaluate biofilms on resins with repeated exposures for 20 passages for the first time. DMAHDM, dimethylaminododecyl methacrylate (DMADDM) and chlorhexidine (CHX) were tested with planktonic bacteria. Biofilms were grown on a resin containing 3% DMAHDM. Minimum-inhibitory concentrations were measured. To detect drug-resistance, the survived bacteria from the previous passage were used as inoculum for the next passage for repeated exposures. S. gordonii developed drug-resistance against DMADDM and CHX, but not against DMAHDM. Biofilm colony-forming units (CFU) on DMAHDM-resin was reduced by 3-4 log; there was no difference from passages 1 to 20 (p > 0.1). No drug-resistance to DMAHDM was detected for all three bacterial species. In conclusion, this study showed that DMAHDM induced no drug-resistance, and DMAHDM-resin reduced biofilm CFU by 3-4 log, with no significant change from 1 to 20 passages. DMAHDM with potent antibacterial activities and no drug-resistance is promising for dental applications.201829615732
9097140.9118Antimicrobial peptides with symmetric structures against multidrug-resistant bacteria while alleviating antimicrobial resistance. In response to the dramatically increasing antimicrobial resistance, a series of new symmetric peptides were designed and synthesized in this study by a "WWW" motif as the symmetric center, arginine as the positive charge amino acid and the terminus symmetrically tagged with hydrophobic amino acids. Amongst the new symmetric peptide FRRW (FRRWWWRRF-NH(2)) presented the highest cell selectivity for bacteria over mammalian cell and exerted excellent antimicrobial potential against a broad of bacteria, especially difficult-to-kill multidrug-resistant strains clinical isolates. FRRW also displayed perfect stability in physiological salt ions and rapid killing speed as well as acted on multiple mechanisms including non-receptor mediated membrane and intra-molecular mechanisms. Importantly, FRRW emerged a low tendency of resistance in contrast to traditional antibiotics ciprofloxacin and gentamicin. What's more, FRRW could resist or alleviate or even reverse the ciprofloxacin- and gentamicin-resistance by changing the permeability of bacterial membrane and inhibiting the efflux pumps of bacteria. Furthermore, FRRW exhibited remarkable effectiveness and higher safety in vivo than polymyxin B. In summary, the new symmetric peptide FRRW was promised to be as a new antimicrobial candidate for overcoming the increasing bacterial resistance.202133610592
746150.9116Novel antimicrobial 3-phenyl-4-phenoxypyrazole derivatives target cell wall lipid intermediates with low mammalian cytotoxicity. The growing crisis of antimicrobial resistance (AMR) underscores the critical need for innovative antimicrobial discoveries. Novel antibiotics targeting the bacterial cell wall remain an attractive area of research, due to their conservation and essentiality in bacteria and their absence in eukaryotic cells. Antibiotics targeting lipid II are of special interest due to the reduced potential for target modification of lipid components and their surface accessibility to inhibitors. In this study, we identified 3-phenyl-4-phenoxypyrazole analogues named PYO12 and PYO12a with bactericidal activity against gram-positive bacteria and low cytotoxicity for different types of mammalian cells. Gram-negative bacteria were resistant to PYO12 activity through extrusion of this compound via efflux pumps. Exposure to PYO12 induces expression of genes involved in resistance to antimicrobials targeting the cell wall, suggesting that PYO12 acts via binding to lipid II or other lipid intermediates involved in peptidoglycan or teichoic acid biosynthesis. Antagonism of PYO12 antibacterial activity by undecaprenyl-pyrophosphate supports the idea that PYO12 may bind to the lipid moiety of lipid II blocking the shuttling of peptidoglycan precursors across the cytoplasmic membrane. These findings open opportunities to further develop these compounds as antibiotics targeting bacterial cell wall synthesis.202541083642
9026160.9116Citral and its derivatives inhibit quorum sensing and biofilm formation in Chromobacterium violaceum. With an upsurge in multidrug resistant bacteria backed by biofilm defence armours, there is a desperate need of new antibiotics with a non-traditional mechanism of action. Targeting bacteria by misguiding them or halting their communication is a new approach that could offer a new way to combat the multidrug resistance problem. Quorum sensing is considered to be the achilles heel of bacteria that has a lot to offer. Since, both quorum sensing and biofilm formation have been related to drug resistance and pathogenicity, in this study we synthesised new derivatives of citral with antiquorum sensing and biofilm disrupting properties. We previously reported antimicrobial and antiquorum sensing activity of citral and herein we report the synthesis and evaluation of citral and its derivatives (CD1-CD3) for antibacterial, antibiofilm and antiquorum sensing potential against Chromobacterium violaceum using standard methods. Preliminary results revealed that CD1 is the most active of all the derivatives. Qualitative and quantitative evaluation of antiquorum sensing activity at sub-inhibitory concentrations of these compounds also revealed high activity for CD1 followed by CD2, CD3 and citral. These compounds also inhibit biofilm formation at subinhibitory concentrations without causing any bacterial growth inhibition. These results were replicated by RT-qPCR with down regulation of the quorum sensing genes when C. violaceum was treated with these test compounds. Overall, the results are quite encouraging, revealing that biofilm and quorum sensing are interrelated processes and also indicating the potential of these derivatives to impede bacterial communication and biofilm formation.202133392626
221170.9116Aminoglycosides versus bacteria--a description of the action, resistance mechanism, and nosocomial battleground. Since 1944, we have come a long way using aminoglycosides as antibiotics. Bacteria also have got them selected with hardier resistance mechanisms. Aminoglycosides are aminocyclitols that kill bacteria by inhibiting protein synthesis as they bind to the 16S rRNA and by disrupting the integrity of bacterial cell membrane. Aminoglycoside resistance mechanisms include: (a) the deactivation of aminoglycosides by N-acetylation, adenylylation or O-phosphorylation, (b) the reduction of the intracellular concentration of aminoglycosides by changes in outer membrane permeability, decreased inner membrane transport, active efflux, and drug trapping, (c) the alteration of the 30S ribosomal subunit target by mutation, and (d) methylation of the aminoglycoside binding site. There is an alarming increase in resistance outbreaks in hospital setting. Our review explores the molecular understanding of aminoglycoside action and resistance with an aim to minimize the spread of resistance.200817657587
6379180.9116Shotgun metagenome guided exploration of anthropogenically driven resistomic hotspots within Lonar soda lake of India. Anthropogenic activities mediated antibiotic resistance genes (ARGs) in the pristine aquatic bodies (lakes) is raising concern worldwide. Long read shotgun sequencing was used to assess taxonomic diversity, distribution of ARGs and metal resistance genes (MRGs) and mobile genetic elements (MGEs) in six sites within hypersaline Lonar soda lake (India) prone to various anthropogenic activities. Proteobacteria and Euryarchaeota were dominant phyla under domain Bacteria and Archaea respectively. Higher abundance of Bacteroidetes was pragmatic at sites 18LN5 and 18LN6. Functional analysis indicated 26 broad-spectrum ARGs types, not reported earlier in this ecosystem. Abundant ARG types identified were multidrug efflux, glycopepetide, bacitracin, tetracycline and aminogylcoside resistance. Sites 18LN1 and 18LN5 depicted 167 and 160 different ARGs subtypes respectively and rpoB2, bcrA, tetA(48), mupA, ompR, patA, vanR and multidrug ABC transporter genes were present in all samples. The rpoB2 gene was dominant in 18LN1, whereas bcrA gene in 18LN2-18LN6 sites. Around 24 MRGs types were detected with higher abundance of arsenic in 18LN1 and copper in 18LN2-18LN6, signifying metal contamination linked to MRGs. The bacterial taxa Pseudomonas, Thioalkalivibrio, Burkholderia, Clostridium, Paenibacillus, Bacillus and Streptomyces were significantly associated with ARGs. This study highlights the resistomic hotspots in the lake for deploying policies for conservation efforts.202032155479
7742190.9115The dissimilarity of antibiotic and quorum sensing inhibitor on activated sludge nitrification system: Microbial communities and antibiotic resistance genes. Effects of antibiotics (azithromycin, AZM, 1-40 mg/L) and quorum sensing inhibitor (QSI, 2(5H)-furanone, 1-40 mg/L) combined pollution with environmental concentration of copper on bacterial/archaeal community and antibiotic resistance genes (ARGs) in activated sludge system were explored. QSI inhibited nitrification more obviously than AZM. AZM and QSI were synergistic inhibitions on bacterial diversity, and AZM inhibited bacterial compositions more than QSI. While, QSI had more impacts on archaeal diversity/compositions. Less interactions among bacteria and archaea communities with Aquimonas as keystone genus. Functional differences in bacteria/archaea communities were little, and AZM had more effects on metabolism. AZM mainly affected nitrifying bacteria (Candidatus Nitrospira nitrificans and Nitrosomonas). Specific denitrifying bacteria were enriched by AZM (Brevundimonas, 1.76-31.69%) and QSI (Comamonas, 0.61-9.61%), respectively. AZM enriched ARGs more easily than QSI and they were antagonistic to proliferation of ARGs. Bacteria were main hosts of ARGs (macrolide-lincosamide-streptogramin B, other/efflux, etc.) and archaea (Methanosphaerula, Methanolobus) carried multiple ARGs.202235306131