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848600.8158Multidrug-resistant plasmid modulates ammonia oxidation efficiency in Nitrosomonas europaea through cyclic di-guanylate and acyl-homoserine lactones pathways. Antibiotic resistance genes present a major public health challenge and have potential implications for global biogeochemical cycles. However, their impacts on biological nitrogen removal systems remain poorly understood. In the ammonia-oxidizing bacteria Nitrosomonas europaea ATCC 19718 harboring the multidrug-resistant plasmid RP4, a significant decrease in ammonia oxidation efficiency was observed, accompanied by markedly elevated levels of cyclic di-guanylate (c-di-GMP) and acyl-homoserine lactones (AHLs), compared to plasmid-free controls. The results demonstrated that c-di-GMP facilitates the secretion of AHLs, while elevated levels of AHLs inhibit the ammonia oxidation efficiency of Nitrosomonas europaea ATCC 19718. These results revealed that RP4 plasmid significantly impaired ammonia oxidation efficiency through the c-di-GMP and AHLs pathways. Our findings indicate that the multidrug-resistant plasmid RP4 adversely affects the nitrogen metabolism of ammonia-oxidizing bacteria, potentially disrupting the nitrogen biogeochemical cycle and posing substantial ecological and environmental risks.202640945801
871610.8075Organophosphorus mineralizing-Streptomyces species underpins uranate immobilization and phosphorus availability in uranium tailings. Phosphate-solubilizing bacteria (PSB) are important but often overlooked regulators of uranium (U) cycling in soil. However, the impact of PSB on uranate fixation coupled with the decomposition of recalcitrant phosphorus (P) in mining land remains poorly understood. Here, we combined gene amplicon sequencing, metagenome and metatranscriptome sequencing analysis and strain isolation to explore the effects of PSB on the stabilization of uranate and P availability in U mining areas. We found that the content of available phosphorus (AP), carbonate-U and Fe-Mn-U oxides in tailings was significantly (P < 0.05) higher than their adjacent soils. Also, organic phosphate mineralizing (PhoD) bacteria (e.g., Streptomyces) and inorganic phosphate solubilizing (gcd) bacteria (e.g., Rhodococcus) were enriched in tailings and soils, but only organic phosphate mineralizing-bacteria substantially contributed to the AP. Notably, most genes involved in organophosphorus mineralization and uranate resistance were widely present in tailings rather than soil. Comparative genomics analyses supported that organophosphorus mineralizing-Streptomyces species could increase soil AP content and immobilize U(VI) through organophosphorus mineralization (e.g., PhoD, ugpBAEC) and U resistance related genes (e.g., petA). We further demonstrated that the isolated Streptomyces sp. PSBY1 could enhance the U(VI) immobilization mediated by the NADH-dependent ubiquinol-cytochrome c reductase (petA) through decomposing organophosphorous compounds. This study advances our understanding of the roles of PSB in regulating the fixation of uranate and P availability in U tailings.202438908177
788020.8051The synergistic mechanism of β-lactam antibiotic removal between ammonia-oxidizing microorganisms and heterotrophs. Nitrifying system is an effective strategy to remove numerous antibiotics, however, the contribution of ammonia-oxidizing bacteria (AOB), ammonia-oxidizing archaea (AOA) and heterotrophs for antibiotic removal are still unclear. In this study, the mechanism of β-lactam antibiotic (cefalexin, CFX) removal was studied in a nitrifying sludge system. Results showed that CFX was synergistically removed by AOB (Nitrosomonas, played a major role) and AOA (Candidatus_Nitrososphaera) through ammonia monooxygenase-mediated co-metabolism, and by heterotrophs (Pseudofulvimonas, Hydrogenophaga, RB41, Thauera, UTCFX1, Plasticicumulans, Phaeodactylibacter) through antibiotic resistance genes (ARGs)-encoded β-lactamases-mediated hydrolysis. Regardless of increased archaeal and heterotrophic CFX removal with the upregulation of amoA in AOA and ARGs, the system exhibited poorer CFX removal performance at 10 mg/L, mainly due to the inhibition of AOB. This study provides new reference for the important roles of heterotrophs and ARGs, opening the possibilities for the application of ARGs in antibiotic biodegradation.202336174754
430.8048Bacteria deplete deoxynucleotides to defend against bacteriophage infection. DNA viruses and retroviruses consume large quantities of deoxynucleotides (dNTPs) when replicating. The human antiviral factor SAMHD1 takes advantage of this vulnerability in the viral lifecycle, and inhibits viral replication by degrading dNTPs into their constituent deoxynucleosides and inorganic phosphate. Here, we report that bacteria use a similar strategy to defend against bacteriophage infection. We identify a family of defensive bacterial deoxycytidine triphosphate (dCTP) deaminase proteins that convert dCTP into deoxyuracil nucleotides in response to phage infection. We also identify a family of phage resistance genes that encode deoxyguanosine triphosphatase (dGTPase) enzymes, which degrade dGTP into phosphate-free deoxyguanosine and are distant homologues of human SAMHD1. Our results suggest that bacterial defensive proteins deplete specific deoxynucleotides (either dCTP or dGTP) from the nucleotide pool during phage infection, thus starving the phage of an essential DNA building block and halting its replication. Our study shows that manipulation of the dNTP pool is a potent antiviral strategy shared by both prokaryotes and eukaryotes.202235817891
65340.8046Connecting Algal Polysaccharide Degradation to Formaldehyde Detoxification. Formaldehyde is a toxic metabolite that is formed in large quantities during bacterial utilization of the methoxy sugar 6-O-methyl-d-galactose, an abundant monosaccharide in the red algal polysaccharide porphyran. Marine bacteria capable of metabolizing porphyran must therefore possess suitable detoxification systems for formaldehyde. We demonstrate here that detoxification of formaldehyde in the marine Flavobacterium Zobellia galactanivorans proceeds via the ribulose monophosphate pathway. Simultaneously, we show that the genes encoding the key enzymes of this pathway are important for maintaining high formaldehyde resistance. Additionally, these genes are upregulated in the presence of porphyran, allowing us to connect porphyran degradation to the detoxification of formed formaldehyde.202235561127
787350.8042Wheat straw pyrochar more efficiently decreased enantioselective uptake of dinotefuran by lettuce and dissemination of antibiotic resistance genes than hydrochar in an agricultural soil. Remediation of soils pollution caused by dinotefuran, a chiral pesticide, is indispensable for ensuring human food security. In comparison with pyrochar, the effect of hydrochar on enantioselective fate of dinotefuran, and antibiotic resistance genes (ARGs) profiles in the contaminated soils remain poorly understood. Therefore, wheat straw hydrochar (SHC) and pyrochar (SPC) were prepared at 220 and 500 °C, respectively, to investigate their effects and underlying mechanisms on enantioselective fate of dinotefuran enantiomers and metabolites, and soil ARG abundance in soil-plant ecosystems using a 30-day pot experiment planted with lettuce. SPC showed a greater reduction effect on the accumulation of R- and S-dinotefuran and metabolites in lettuce shoots than SHC. This was mainly resulted from the lowered soil bioavailability of R- and S-dinotefuran due to adsorption/immobilization by chars, together with the char-enhanced pesticide-degrading bacteria resulted from increased soil pH and organic matter content. Both SPC and SHC efficiently reduced ARG levels in soils, owing to lowered abundance of ARG-carrying bacteria and declined horizontal gene transfer induced by decreased dinotefuran bioavailability. The above results provide new insights for optimizing char-based sustainable technologies to mitigate pollution of dinotefuran and spread of ARGs in agroecosystems.202336996986
787960.8040Multidrug-resistant plasmid RP4 increases NO and N(2)O yields via the electron transport system in Nitrosomonas europaea ammonia oxidation. Antibiotic resistance genes (ARGs) have recently become an important public health problem and therefore several studies have characterized ARG composition and distribution. However, few studies have assessed their impact on important functional microorganisms in the environment. Therefore, our study sought to investigate the mechanisms through which multidrug-resistant plasmid RP4 affected the ammonia oxidation capacity of ammonia-oxidizing bacteria, which play a key role in the nitrogen cycle. The ammonia oxidation capacity of N. europaea ATCC25978 (RP4) was significantly inhibited, and NO and N(2)O were produced instead of nitrite. Our findings demonstrated that the decrease in electrons from NH(2)OH decreased the ammonia monooxygenase (AMO) activity, leading to a decrease in ammonia consumption. In the ammonia oxidation process, N. europaea ATCC25978 (RP4) exhibited ATP and NADH accumulation. The corresponding mechanism was the overactivation of Complex Ⅰ, ATPase, and the TCA cycle by the RP4 plasmid. The genes encoding TCA cycle enzymes related to energy generation, including gltA, icd, sucD, and NE0773, were upregulated in N. europaea ATCC25978 (RP4). These results demonstrate the ecological risks of ARGs, including the inhibition of the ammonia oxidation process and an increased production of greenhouse gases such as NO and N(2)O.202337421866
811170.8016Effect of alkaline-thermal pretreatment on biodegradable plastics degradation and dissemination of antibiotic resistance genes in co-compost system. Biodegradable plastics (BDPs) are an eco-friendly alternative to traditional plastics in organic waste, but their microbial degradation and impact on antibiotic resistance genes (ARGs) transmission during co-composting remain poorly understood. This study examines how alkaline-thermal pretreatment enhances BDPs degradation and influences the fate of ARGs and mobile genetic elements (MGEs) in co-composting. Pretreatment with 0.1 mol/L NaOH at 100℃ for 40 minutes increased the surface roughness and hydrophilicity of BDPs while reducing their molecular weight and thermal stability. Incorporating pretreated BDPs film (8 g/kg-TS) into the compost reduced the molecular weight of the BDPs by 59.70 % during the maturation stage, facilitating compost heating and prolonging the thermophilic stage. However, incomplete degradation of BDPs releases numerous smaller-sized microplastics, which can act as carriers for microorganisms, facilitating the dissemination of ARGs across environments and posing significant ecological and public health risks. Metagenomic analysis revealed that pretreatment enriched plastic-degrading bacteria, such as Thermobifida fusca, on BDPs surfaces and accelerated microbial plastic degradation during the thermophilic stage, but also increased ARGs abundance. Although pretreatment significantly reduced MGEs abundance (tnpA, IS19), the risk of ARGs dissemination remained. Three plastic-degrading bacteria (Pigmentiphaga sp002188465, Bacillus clausii, and Bacillus altitudinis) were identified as ARGs hosts, underscoring the need to address the risk of horizontal gene transfer of ARGs associated with pretreatment in organic waste management.202539970645
855880.8006Mitigating the vertical migration and leaching risks of antibiotic resistance genes through insect fertilizer application. The leaching and vertical migration risks of antibiotic resistance genes (ARGs) from fertilized soil to groundwater poses a significant threat to ecological and public safety. Insect fertilizer, particularly black soldier fly organic fertilizer (BOF), renowned for its minimal antibiotic resistance, emerge as a promising alternative for sustainable agricultural fertilization. This study employs soil-column leaching experiments to evaluate the impact of BOF on the leaching behavior of ARGs. Our results reveal that BOF significantly reduces the leaching risks of ARGs by 22.1 %-49.3 % compared to control organic fertilizer (COF). Moreover, BOF promotes the leaching of beneficial Bacillus and, according to random forest analysis, is the most important factor in predicting ARG profiles (3.02 % increase in the MSE). Further network analysis and mantel tests suggest that enhanced nitrogen metabolism in BOF leachates could foster Bacillus biofilm formation, thereby countering antibiotic-resistant bacteria (ARB) and mitigating antibiotic resistance. In addition, linear regression analysis revealed that Bacillus biofilm-associated genes pgaD (biofilm PGA synthesis protein), slrR (biofilm formation regulator), and kpsC (capsular polysaccharide export protein) were identified as pivotal in the elimination of ARGs, which can serve as effective indicators for assessing antibiotic resistance in groundwater. Collectively, this study demonstrates that BOF as an environmentally friendly fertilizer could markedly reduce the vertical migration risks of ARGs and proposes Bacillus biofilm formation related genes as reliable indicators for monitoring antibiotic resistance in groundwater.202540086570
52390.7997Sulfide-carbonate-mineralized functional bacterial consortium for cadmium removal in flue gas. Sulfide-carbonate-mineralized functional bacterial consortium was constructed for flue gas cadmium biomineralization. A membrane biofilm reactor (MBfR) using the bacterial consortium containing sulfate reducing bacteria (SRB) and denitrifying bacteria (DNB) was investigated for flue gas cadmium (Cd) removal. Cadmium removal efficiency achieved 90%. The bacterial consortium containing Citrobacter, Desulfocurvus and Stappia were dominated for cadmium resistance-nitrate-sulfate reduction. Under flue gas cadmium stress, ten cadmium resistance genes (czcA, czcB, czcC, czcD, cadA, cadB, cadC, cueR, copZ, zntA), and seven genes related to sulfate reduction, increased in abundance; whereas others, nine genes related to denitrification, decreased, indicating that cadmium stress was advantageous to sulfate reduction in the competition with denitrification. A bacterial consortium could capable of simultaneously cadmium resistance, sulfate reduction and denitrification. Microbial induced carbonate precipitation (MICP) and biological adsorption process would gradually yield to sulfide-mineralized process. Flue gas cadmium could transform to Cd-EPS, cadmium carbonate (CdCO(3)) and cadmium sulfide (CdS) bioprecipitate. The functional bacterial consortium was an efficient and eco-friendly bifunctional bacterial consortium for sulfide-carbonate-mineralized of cadmium. This provides a green and low-carbon advanced treatment technology using sulfide-carbonate-mineralized functional bacterial consortium for the removal of cadmium or other hazardous heavy metal contaminants in flue gas.202439019186
516100.7992Role of Iron-Containing Alcohol Dehydrogenases in Acinetobacter baumannii ATCC 19606 Stress Resistance and Virulence. Most bacteria possess alcohol dehydrogenase (ADH) genes (Adh genes) to mitigate alcohol toxicity, but these genes have functions beyond alcohol degradation. Previous research has shown that ADH can modulate quorum sensing in Acinetobacter baumannii, a rising opportunistic pathogen. However, the number and nature of Adh genes in A. baumannii have not yet been fully characterized. We identified seven alcohol dehydrogenases (NAD(+)-ADHs) from A. baumannii ATCC 19606, and examined the roles of three iron-containing ADHs, ADH3, ADH4, and ADH6. Marker-less mutation was used to generate Adh3, Adh4, and Adh6 single, double, and triple mutants. Disrupted Adh4 mutants failed to grow in ethanol-, 1-butanol-, or 1-propanol-containing mediums, and recombinant ADH4 exhibited strongest activity against ethanol. Stress resistance assays with inorganic and organic hydroperoxides showed that Adh3 and Adh6 were key to oxidative stress resistance. Virulence assays performed on the Galleria mellonella model organism revealed that Adh4 mutants had comparable virulence to wild-type, while Adh3 and Adh6 mutants had reduced virulence. The results suggest that ADH4 is primarily involved in alcohol metabolism, while ADH3 and ADH6 are key to stress resistance and virulence. Further investigation into the roles of other ADHs in A. baumannii is warranted.202134576087
7888110.7990Microecology of aerobic denitrification system construction driven by cyclic stress of sulfamethoxazole. The construction of aerobic denitrification (AD) systems in an antibiotic-stressed environment is a serious challenge. This study investigated strategy of cyclic stress with concentration gradient (5-30 mg/L) of sulfamethoxazole (SMX) in a sequencing batch reactor (SBR), to achieve operation of AD. Total nitrogen removal efficiency of system increased from about 10 % to 95 %. Original response of abundant-rare genera to antibiotics was changed by SMX stress, particularly conditionally rare or abundant taxa (CRAT). AD process depends on synergistic effect of heterotrophic nitrifying aerobic denitrification bacteria (Paracoccus, Thauera, Hypomicrobium, etc). AmoABC, napA, and nirK were functionally co-expressed with multiple antibiotic resistance genes (ARGs) (acrR, ereAB, and mdtO), facilitating AD process. ARGs and TCA cycling synergistically enhance the antioxidant and electron transport capacities of AD process. Antibiotic efflux pump mechanism played an important role in operation of AD. The study provides strong support for regulating activated sludge to achieve in situ AD function.202438710419
7875120.7990Phenacetin enhanced the inorganic nitrogen removal performance of anammox bacteria naturally in-situ enriched system. Among the earliest synthetic antipyretic drugs, phenacetin (PNCT) could be used as the novel partial nitrification (PN) inhibitor to effectively inhibit nitrite-oxidizing bacteria (NOB). In practical application, the rapidly starting of PN could provide stable source of nitrite for anaerobic ammonium oxidation (anammox) process. However, impact of PNCT on anaerobic ammonia oxidizing bacteria (AnAOB) and its underlying mechanisms were not clear. In this research, totally 14 times of PNCT aerobic soaking treatment were performed in the AnAOB naturally enrichment system to improve total inorganic nitrogen removal efficiency (TINRE). After once of PNCT treatment, TINRE rose from 61.89 % to 79.93 %. After 14 times of PNCT treatment, NOB Nitrospira relative abundance decreased from 9.82 % to 0.71 %, though Candidatus Brocadia relative abundance also declined, it might gradually adjust to PNCT by converting the leading oligotype species. The activity and relative abundances of NOB were reduced by PNCT via decreasing the abundances of genes amoA and nxrB, enzymes NxrA and NxrB. Moreover, Candidatus Jettenia and Ca. Brocadia might be the potential host of qacH-01 and they played the crucial role in the shaping profile of antibiotic resistance genes (ARGs). The explosive propagation or transmission of ARGs might not take place after PNCT treatment.202439566627
7851130.7987Breaking antibiotic resistance: Sunlight-powered calcium peroxide for dual bactericidal and genetic elimination. Antibiotic-resistant bacteria (ARB) and associated antibiotic resistance genes (ARGs) have emerged as critical waterborne contaminants, posing serious public health risks. This study proposes a disinfection strategy through sunlight powered calcium peroxide (CaO(2)) treatment that simultaneously inactivates ARB and degrades ARGs in aquatic environments. Solar irradiation combined with CaO(2) (3.0 mM) activates dual mechanisms: alkaline-driven microbial inactivation (pH increase from 6.4 to 8.2 within 30 min) and ROS-mediated oxidative damage (ROS: (•)OH, H(2)O(2), (1)O(2) and O(2)(•-)), achieving complete 5-log inactivation of tetracycline and sulfonamides-resistant E. coli (TSRE). ARGs (tetA and sul2) showed 70-80 % reduction in absolute abundance, although the log removal did not exceed 1-log. Compared to sunlight alone, the addition of CaO(2) significantly enhanced disinfection efficiency. Alkaline and ROS-induced oxidative stress caused membrane lipid breakdown, protein denaturation, and suppression of antioxidant enzymes, along with DNA damage, lipid peroxidation, and enzyme inactivation. These effects increased membrane permeability, impaired bacterial recovery by downregulating DNA repair genes, and disrupted cellular integrity, ultimately limiting ARGs persistence. These findings highlight the synergistic effect of alkaline and oxidative stress in effectively inactivating ARB and degrading ARGs, positioning sunlight powered CaO(2) as a promising, highly efficient disinfection strategy for environmental water treatment.202540876436
7874140.7987Phenacetin promoted the rapid start-up and stable maintenance of partial nitrification: Responses of nitrifiers and antibiotic resistance genes. Phenacetin (PNCT) belongs to one of the earliest synthetic antipyretics. However, impact of PNCT on nitrifying microorganisms in wastewater treatment plants and its potential microbial mechanism was still unclear. In this study, PN could be initiated within six days by PNCT anaerobic soaking treatment (8 mg/L). In order to improve the stable performance of PN, 21 times of PNCT aerobic soaking treatment every three days was conducted and PN was stabilized for 191 days. After PN was damaged, ten times of PNCT aerobic soaking treatment every three days was conducted and PN was recovered after once soaking, maintained over 88 days. Ammonia oxidizing bacteria might change the dominant oligotype to gradually adjust to PNCT, and the increase of abundance and activity of Nitrosomonas promoted the initiation of PN. For nitrite-oxidizing bacteria (NOB), the increase of Candidatus Nitrotoga and Nitrospira destroyed PN, but PN could be recovered after once aerobic soaking illustrating NOB was not resistant to PNCT. KEGG and COG analysis suggested PNCT might disrupt rTCA cycle of Nitrospira, resulting in the decrease of relative abundance of Nitrospira. Moreover, PNCT did not lead to the sharp increase of absolute abundances of antibiotic resistance genes (ARGs), and the risk of ARGs transmission was negligible.202438744392
8492150.7985Promotion effects and mechanisms of molybdenum disulfide on the propagation of antibiotic resistance genes in soil. The rapid development of nanotechnology has aroused considerable attentions toward understanding the effects of engineered nanomaterials (ENMs) on the propagation of antibiotic resistance. Molybdenum disulfide (MoS(2)) is an extensively used ENM and poses potential risks associated with environmental exposure; nevertheless, the role of MoS(2) toward antibiotic resistance genes (ARGs) transfer remains largely unknown. Herein, it was discovered that MoS(2) nanosheets accelerated the horizontal transfer of RP4 plasmid across Escherichia coli in a dose-dependent manner (0.5-10 mg/L), with the maximum transfer frequency 2.07-fold higher than that of the control. Integration of physiological, transcriptomics, and metabolomics analyses demonstrated that SOS response in bacteria was activated by MoS(2) due to the elevation of oxidative damage, accompanied by cell membrane permeabilization. MoS(2) promoted bacterial adhesion and intercellular contact via stimulating the secretion of extracellular polysaccharides. The ATP levels were maximally increased by 305.7 % upon exposure to MoS(2), and the expression of plasmid transfer genes was up-regulated, contributing to the accelerated plasmid conjugation and increased ARG abundance in soil. Our findings highlight the roles of emerging ENMs (e.g., MoS(2)) in ARGs dissemination, which is significant for the safe applications and risk management of ENMs under the development scenarios of nanotechnology.202337062264
8487160.7985Mechanisms of nano zero-valent iron in enhancing dibenzofuran degradation by a Rhodococcus sp.: Trade-offs between ATP production and protection against reactive oxygen species. Nano zero-valent iron (nZVI) can enhance pollutants biodegradation, but it displays toxicity towards microorganisms. Gram-positive (G(+)) bacteria exhibit greater resistance to nZVI than Gram-negative bacteria. However, mechanisms of nZVI accelerating pollutants degradation by G(+) bacteria remain unclear. Herein, we explored effects of nZVI on a G(+) bacterium, Rhodococcus sp. strain p52, and mechanisms by which nZVI accelerates biodegradation of dibenzofuran, a typical polycyclic aromatic compound. Electron microscopy and energy dispersive spectroscopy analysis revealed that nZVI could penetrate cell membranes, which caused damage and growth inhibition. nZVI promoted dibenzofuran biodegradation at certain concentrations, while higher concentration functioned later due to the delayed reactive oxygen species (ROS) mitigation. Transcriptomic analysis revealed that cells adopted response mechanisms to handle the elevated ROS induced by nZVI. ATP production was enhanced by accelerated dibenzofuran degradation, providing energy for protein synthesis related to antioxidant stress and damage repair. Meanwhile, electron transport chain (ETC) was adjusted to mitigate ROS accumulation, which involved downregulating expression of ETC complex I-related genes, as well as upregulating expression of the genes for the ROS-scavenging cytochrome bd complex and ETC complex II. These findings revealed the mechanisms underlying nZVI-enhanced biodegradation by G(+) bacteria, offering insights into optimizing bioremediation strategies involving nZVI.202539549579
7887170.7984Double-edged sword effects of sulfate reduction process in sulfur autotrophic denitrification system: Accelerating nitrogen removal and promoting antibiotic resistance genes spread. This study proposed the double-edged sword effects of sulfate reduction process on nitrogen removal and antibiotic resistance genes (ARGs) transmission in sulfur autotrophic denitrification system. Excitation-emission matrix-parallel factor analysis identified the protein-like fraction in soluble microbial products as main endogenous organic matter driving the sulfate reduction process. The resultant sulfide tended to serve as bacterial modulators, augmenting electron transfer processes and mitigating oxidative stress, thereby enhancing sulfur oxidizing bacteria (SOB) activity, rather than extra electron donors. The cooperation between SOB and heterotroph (sulfate reducing bacteria (SRB) and heterotrophic denitrification bacteria (HDB)) were responsible for advanced nitrogen removal, facilitated by multiple metabolic pathways including denitrification, sulfur oxidation, and sulfate reduction. However, SRB and HDB were potential ARGs hosts and assimilatory sulfate reduction pathway positively contributed to ARGs spread. Overall, the sulfate reduction process in sulfur autotrophic denitrification system boosted nitrogen removal process, but also increased the risk of ARGs transmission.202439122125
518180.7983Bacitracin and nisin resistance in Staphylococcus aureus: a novel pathway involving the BraS/BraR two-component system (SA2417/SA2418) and both the BraD/BraE and VraD/VraE ABC transporters. Two-component systems (TCSs) are key regulatory pathways allowing bacteria to adapt their genetic expression to environmental changes. Bacitracin, a cyclic dodecylpeptide antibiotic, binds to undecaprenyl pyrophosphate, the lipid carrier for cell wall precursors, effectively inhibiting peptidoglycan biosynthesis. We have identified a novel and previously uncharacterized TCS in the major human pathogen Staphylococcus aureus that we show to be essential for bacitracin and nisin resistance: the BraS/BraR system (Bacitracin resistance associated; SA2417/SA2418). The braRS genes are located immediately upstream from genes encoding an ABC transporter, accordingly designated BraDE. We have shown that the BraSR/BraDE module is a key bacitracin and nisin resistance determinant in S. aureus. In the presence of low antibiotic concentrations, BraSR activate transcription of two operons encoding ABC transporters: braDE and vraDE. We identified a highly conserved imperfect palindromic sequence upstream from the braDE and vraDE promoter sequences, essential for their transcriptional activation by BraSR, suggesting it is the likely BraR binding site. We demonstrated that the two ABC transporters play distinct and original roles in antibiotic resistance: BraDE is involved in bacitracin sensing and signalling through BraSR, whereas VraDE acts specifically as a detoxification module and is sufficient to confer bacitracin and nisin resistance when produced on its own. We show that these processes require functional BraD and VraD nucleotide-binding domain proteins, and that the large extracellular loop of VraE confers its specificity in bacitracin resistance. This is the first example of a TCS associated with two ABC transporters playing separate roles in signal transduction and antibiotic resistance.201121696458
8571190.7983Efficient elimination of antibiotics and antibiotic resistance genes in hyperthermophilic sludge composting. Composting is widely applied in recycling ever-increasing sewage sludge. However, the insufficient elimination of antibiotics and antibiotic resistance genes (ARGs) in conventional compost fertilizer poses considerable threat to agriculture safety and human health. Here we investigated the efficacy and potential mechanisms in the removal of antibiotics and ARGs from sludge in hyperthermophilic composting (HTC) plant. Our results demonstrated that the HTC product was of high maturity. HTC led to complete elimination of antibiotics and potential pathogens, as well as removal of 98.8 % of ARGs and 88.1 % of mobile genetic elements (MGEs). The enrichment of antibiotic-degrading candidates and related metabolic functions during HTC suggested that biodegradation played a crucial role in antibiotic removal. Redundancy analysis (RDA) and structural equation modelling (SEM) revealed that the reduction of ARGs was attributed to the decline of ARG-associated bacteria, mainly due to the high-temperature selection. These findings highlight the feasibility of HTC in sludge recycling and provide a deeper understanding of its mechanism in simultaneous removal of antibiotics and ARGs.202439217943