# | Rank | Similarity | Title + Abs. | Year | PMID |
|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | 5 |
| 8596 | 0 | 0.9938 | Stringent response-mediated ferroptosis-like death resistance underlies Novosphingobium persistence during ciprofloxacin stress. Antibiotics, as emerging hazardous materials in the environment, pose significant risks to ecosystems and contribute to the spread of antibiotic-resistant bacteria. Although extensive knowledge has been accumulated on antibiotic-resistance mechanisms in individual bacteria, less is understood about how the bacterial communities respond to antibiotic exposure under natural environmental conditions, where nutrient supplies are often limited and fluctuating. Here, we report that Novosphingobium dominated in a wetland bacterial community under 1 µg/mL ciprofloxacin (CIP) exposure and persisted during DL-serine hydroxamate-induced starvation, where the stringent response alarmer (p)ppGpp was detected. Metagenome sequencing revealed that genes associated with siderophore transport, cytochrome c, and glutathione S-transferase were significantly enriched in Novosphingobium, linking its dominance under CIP stress to iron homeostasis and oxidative stress responses. Further study on the survival mechanism of Novosphingobium pentaromativorans US6-1 under 8 µg/mL CIP stress demonstrated that stringent response regulated the growth rate and maintained cell viability by suppressing the TCA cycle and oxidative phosphorylation, deterring the entry of CIP and siderophore into cells, reducing intracellular ferrous iron and malondialdehyde, and balancing cellular redox status, thereby protecting cells from ferroptosis-like death. This study is the first to report Novosphingobium's dominance and persistence in a bacterial community during CIP stress in natural environmental conditions and to propose the stringent response-mediated ferroptosis-like death resistance as one of its key survival mechanisms.IMPORTANCEAntibiotics in the environment are increasingly recognized as a new class of pollutants that accelerate the evolutionary selection of antibiotic-resistant bacteria. However, little is known about how this selection occurs under natural conditions, including how specific bacteria taxa and mechanisms respond to particular antibiotics. This study reveals for the first time the selection effect of CIP on Novosphingobium under nutrient-limited conditions, during which stringent response and iron homeostasis play important roles. An innovative linkage between stringent response and ferroptosis-like death resistance is proposed in N. pentaromativorans US6-1, which serves as the CIP resistance mechanism for Novosphingobium. These findings may help inform strategies to combat antimicrobial resistance in the natural environment. | 2025 | 40952106 |
| 6779 | 1 | 0.9934 | Intestinal flora metabolites indole-3-butyric acid and disodium succinate promote IncI2 mcr-1-carrying plasmid transfer. INTRODUCTION: Plasmid-driven horizontal transfer of resistance genes in bacterial communities is a major factor in the spread of resistance worldwide. The gut microbiome, teeming with billions of microorganisms, serves as a reservoir for resistance genes. The metabolites of gut microorganisms strongly influence the physiology of their microbial community, but the role of the metabolites in the transfer of resistance genes remains unclear. METHODS: A dual-fluorescence conjugation model was established. We assessed the effects of different concentrations of indole-3-butyric acid (IBA) and disodium succinate (DS) on plasmid transfer using conjugation assays. The growth of bacteria (donors, recipients, and transconjugants), the reactive oxygen species (ROS) levels and membrane permeability were measured under IBA and DS exposure. The plasmid copy number, and transcriptional levels of conjugation-related genes (including the related genes of the regulation of ROS production, the SOS response, cell membrane permeability, pilus generation, ATP synthesis, and the type IV secretion system (T4SS) ) were evaluated by qPCR. RESULTS: In this study, we demonstrated that IBA and DS at low concentrations, which can also be ingested through diet, enhance the interspecies transfer ratio of IncI2 mcr-1-carrying plasmid in Escherichia coli. At 20 mg/L, the transfer ratios in the presence of IBA or DS increased by 2.5- and 2.7-fold compared to that of the control, respectively. Exposure to this concentration of IBA or DS increased the production of reactive oxygen species (ROS), the SOS response, cell membrane permeability, and plasmid copy number. The transcription of genes of the related pathways and of pilus, ATP, and the T4SS was upregulated. DISCUSSION: Our findings revealed that low-dose gut microbiota metabolites-particularly those with dietary origins-promote plasmid-mediated resistance gene dissemination through multifaceted mechanisms involving oxidative stress, SOS activation, and conjugation machinery enhancement. This highlights potential public health risks associated with microbiota metabolites, especially those utilized in food production. | 2025 | 40529306 |
| 6724 | 2 | 0.9932 | A symbiotic bacterium regulates the detoxification metabolism of deltamethrin in Aedes albopictus. The mosquito Aedes albopictus is an important vector of dengue, chikungunya, and Zika; and is a globally distributed invasive mosquito with increasing resistance to insecticides, thereby posing a serious risk to global public health. Symbiotic gut bacteria have been shown to be related to insecticide resistance, but knowledge is still limited for A. albopictus. Here, we explored the role of Serratia marcescens, a gut symbiotic bacterium, in the resistance of A. albopictus to the insecticide deltamethrin. Using 16S-rRNA sequencing we found that S. marcescens was significantly enriched in A. albopictus after deltamethrin exposure, and that resistance increased after S. marcescens enrichment. The enzymatic activities of mixed-function oxidase (MFO) and glutathione S-transferase (GST), two important detoxification enzymes, were higher in the bacteria-enriched mosquitoes. The expressions of ABCG4 and GSTD1, two genes related to detoxification metabolism, were up-regulated following S. marcescens infection and after deltamethrin exposure, as assayed using RNA-seq. The up-regulation of these two genes was most significant in midgut and Malpighian tubules. Our results suggest that S. marcescens infection could enhance deltamethrin resistance in A. albopictus by increasing detoxification metabolism; of interest for designing more efficient mosquito control measures. | 2025 | 40500053 |
| 8603 | 3 | 0.9932 | Ketoprofen promotes the conjugative transfer of antibiotic resistance among antibiotic resistant bacteria in natural aqueous environments. The emergence and spread of antibiotic resistance in the environment pose a serious threat to global public health. It is acknowledged that non-antibiotic stresses, including disinfectants, pharmaceuticals and organic pollutants, play a crucial role in horizontal transmission of antibiotic resistance genes (ARGs). Despite the widespread presence of non-steroidal anti-inflammatory drugs (NSAIDs), notably in surface water, their contributions to the transfer of ARGs have not been systematically explored. Furthermore, previous studies have primarily concentrated on model strains to investigate whether contaminants promote the conjugative transfer of ARGs, leaving the mechanisms of ARG transmission among antibiotic resistant bacteria in natural aqueous environments under the selective pressures of non-antibiotic contaminants remains unclear. In this study, the Escherichia coli (E. coli) K12 carrying RP4 plasmid was used as the donor strain, indigenous strain Aeromonas veronii containing rifampicin resistance genes in Taihu Lake, and E. coli HB101 were used as receptor strains to establish inter-genus and intra-genus conjugative transfer systems, examining the conjugative transfer frequency under the stress of ketoprofen. The results indicated that ketoprofen accelerated the environmental spread of ARGs through several mechanisms. Ketoprofen promoted cell-to-cell contact by increasing cell surface hydrophobicity and reducing cell surface charge, thereby mitigating cell-to-cell repulsion. Furthermore, ketoprofen induced increased levels of reactive oxygen species (ROS) production, activated the DNA damage-induced response (SOS), and enhanced cell membrane permeability, facilitating ARG transmission in intra-genus and inter-genus systems. The upregulation of outer membrane proteins, oxidative stress, SOS response, mating pair formation (Mpf) system, and DNA transfer and replication (Dtr) system related genes, as well as the inhibition of global regulatory genes, all contributed to higher transfer efficiency under ketoprofen treatment. These findings served as an early warning for a comprehensive assessment of the roles of NSAIDs in the spread of antibiotic resistance in natural aqueous environments. | 2024 | 39103039 |
| 7661 | 4 | 0.9932 | Heavy Metal Pollution Impacts Soil Bacterial Community Structure and Antimicrobial Resistance at the Birmingham 35th Avenue Superfund Site. Heavy metals (HMs) are known to modify bacterial communities both in the laboratory and in situ. Consequently, soils in HM-contaminated sites such as the U.S. Environmental Protection Agency (EPA) Superfund sites are predicted to have altered ecosystem functioning, with potential ramifications for the health of organisms, including humans, that live nearby. Further, several studies have shown that heavy metal-resistant (HMR) bacteria often also display antimicrobial resistance (AMR), and therefore HM-contaminated soils could potentially act as reservoirs that could disseminate AMR genes into human-associated pathogenic bacteria. To explore this possibility, topsoil samples were collected from six public locations in the zip code 35207 (the home of the North Birmingham 35th Avenue Superfund Site) and in six public areas in the neighboring zip code, 35214. 35027 soils had significantly elevated levels of the HMs As, Mn, Pb, and Zn, and sequencing of the V4 region of the bacterial 16S rRNA gene revealed that elevated HM concentrations correlated with reduced microbial diversity and altered community structure. While there was no difference between zip codes in the proportion of total culturable HMR bacteria, bacterial isolates with HMR almost always also exhibited AMR. Metagenomes inferred using PICRUSt2 also predicted significantly higher mean relative frequencies in 35207 for several AMR genes related to both specific and broad-spectrum AMR phenotypes. Together, these results support the hypothesis that chronic HM pollution alters the soil bacterial community structure in ecologically meaningful ways and may also select for bacteria with increased potential to contribute to AMR in human disease. IMPORTANCE Heavy metals cross-select for antimicrobial resistance in laboratory experiments, but few studies have documented this effect in polluted soils. Moreover, despite decades of awareness of heavy metal contamination at the EPA Superfund site in North Birmingham, Alabama, this is the first analysis of the impact of this pollution on the soil microbiome. Specifically, this work advances the understanding of the relationship between heavy metals, microbial diversity, and patterns of antibiotic resistance in North Birmingham soils. Our results suggest that polluted soils carry a risk of increased exposure to antibiotic-resistant infections in addition to the direct health consequences of heavy metals. Our work provides important information relevant to both political and scientific efforts to advance environmental justice for the communities that call Superfund neighborhoods home. | 2023 | 36951567 |
| 6726 | 5 | 0.9931 | A symbiotic gut bacterium enhances Aedes albopictus resistance to insecticide. BACKGROUND: The increasing insecticide resistance of Aedes albopictus puts many countries in Asia and Africa, including China, at great risk of a mosquito-borne virus epidemic. To date, a growing number of researches have focused on the relationship between intestinal symbiotic bacteria and their hosts' resistance to insecticides. This provides a novel aspect to the study of resistant mechanisms. METHODS/FINDINGS: This study reveals significant composition and dynamic changes in the intestinal symbiotic bacteria of Ae. albopictus between the resistant and susceptible strains based on full-length sequencing technology. The relative abundance of Serratia oryzae was significantly higher in the resistance strain than in the susceptible strains; also, the relative abundance of S. oryzae was significantly higher in deltamethrin-induced Ae. albopictus than in their counterpart. These suggested that S. oryzae may be involved in the development of insecticide resistance in Ae. albopictus. To explore the insecticide resistance mechanism, adult mosquitoes were fed with GFP-tagged S. oryzae, which resulted in stable bacterial enrichment in the mosquito gut without affecting the normal physiology, longevity, oviposition, and hatching rates of the host. The resistance measurements were made based on bioassays as per the WHO guidelines. The results showed that the survival rate of S. oryzae-enriched Ae. albopictus was significantly higher than the untreated mosquitoes, indicating the enhanced resistance of S. oryzae-enriched Ae. albopictus. Also, the activities of three metabolic detoxification enzymes in S. oryzae-enriched mosquitoes were increased to varying degrees. Meanwhile, the activity of extracellular enzymes released by S. oryzae was measured, but only carboxylesterase activity was detected. HPLC and UHPLC were respectively used to measure deltamethrin residue concentration and metabolite qualitative analysis, showing that the deltamethrin degradation efficiency of S. oryzae was positively correlated with time and bacterial amount. Deltamethrin was broken down into 1-Oleoyl-2-hydroxy-sn-glycero-3-PE and 2',2'-Dibromo-2'-deoxyguanosine. Transcriptome analysis revealed that 9 cytochrome P450s, 8 GSTs and 7 CarEs genes were significantly upregulated. CONCLUSIONS: S. oryzae can be accumulated into adult Ae. albopictus by artificial feeding, which enhances deltamethrin resistance by inducing the metabolic detoxification genes and autocrine metabolic enzymes. S. oryzae is vertically transmitted in Ae. albopictus population. Importantly, S. oryzae can degrade deltamethrin in vitro, and use deltamethrin as the sole carbon source for their growths. Therefore, in the future, S. oryzae may also be commercially used to break down the residual insecticides in the farmland and lakes to protect the environment. | 2022 | 35245311 |
| 8900 | 6 | 0.9931 | Adaptive Resistance Mutations at Suprainhibitory Concentrations Independent of SOS Mutagenesis. Emergence of resistant bacteria during antimicrobial treatment is one of the most critical and universal health threats. It is known that several stress-induced mutagenesis and heteroresistance mechanisms can enhance microbial adaptation to antibiotics. Here, we demonstrate that the pathogen Bartonella can undergo stress-induced mutagenesis despite the fact it lacks error-prone polymerases, the rpoS gene and functional UV-induced mutagenesis. We demonstrate that Bartonella acquire de novo single mutations during rifampicin exposure at suprainhibitory concentrations at a much higher rate than expected from spontaneous fluctuations. This is while exhibiting a minimal heteroresistance capacity. The emerged resistant mutants acquired a single rpoB mutation, whereas no other mutations were found in their whole genome. Interestingly, the emergence of resistance in Bartonella occurred only during gradual exposure to the antibiotic, indicating that Bartonella sense and react to the changing environment. Using a mathematical model, we demonstrated that, to reproduce the experimental results, mutation rates should be transiently increased over 1,000-folds, and a larger population size or greater heteroresistance capacity is required. RNA expression analysis suggests that the increased mutation rate is due to downregulation of key DNA repair genes (mutS, mutY, and recA), associated with DNA breaks caused by massive prophage inductions. These results provide new evidence of the hazard of antibiotic overuse in medicine and agriculture. | 2021 | 34175952 |
| 8513 | 7 | 0.9931 | Chlorine disinfection facilitates natural transformation through ROS-mediated oxidative stress. The bacterial infection that involves antimicrobial resistance is a rising global threat to public health. Chlorine-based water disinfection processes can inactivate antibiotic resistant bacteria. However, at the same time, these processes may cause the release of antibiotic resistance genes into the water as free DNA, and consequently increase the risk to disseminate antibiotic resistance via natural transformation. Presently, little is known about the contribution of residual chlorine affecting the transformation of extracellular antibiotic resistance genes (ARGs). This study investigates whether chloramine and free chlorine promote the transformation of ARGs and how this may occur. We reveal that both chloramine and free chlorine, at practically relevant concentrations, significantly stimulated the transformation of plasmid-encoded ARGs by the recipient Acinetobacter baylyi ADP1, by up to a 10-fold increase. The underlying mechanisms underpinning the increased transformations were revealed. Disinfectant exposure induced a series of cell responses, including increased levels of reactive oxygen species (ROS), bacterial membrane damage, ROS-mediated DNA damage, and increased stress response. These effects thus culminated in the enhanced transformation of ARGs. This promoted transformation was observed when exposing disinfectant-pretreated A. baylyi to free plasmid. In contrast, after pretreating free plasmid with disinfectants, the transformation of ARGs decreased due to the damage of plasmid integrity. These findings provide important insight on the roles of disinfectants affecting the horizontal transfer of ARGs, which could be crucial in the management of antibiotic resistance in our water systems. | 2021 | 33941886 |
| 6772 | 8 | 0.9931 | Disinfectants facilitate the transformation of exogenous antibiotic resistance genes via multiple pathways. The prevalence and spread of multidrug-resistant (MDR) bacteria pose a global challenge to public health. Natural transformation is one of the essential ways for horizontal transfer of antibiotic resistance genes (ARGs). Although disinfectants are frequently used during COVID-19, little is known about whether these disinfectants are associated with the transformation of plasmid-borne ARGs. In our study, we assessed the effect of some disinfectants on bacterial transformation using resistance plasmids as extracellular DNA and E. coli DH5α as the recipient bacteria. The results showed that these disinfectants at environmentally relevant concentrations, including benzalkonium bromide (BB), benzalkonium chloride (BC) and polyhexamethylene guanidine hydrochloride (PHMG), significantly enhanced the transformation of plasmid-encoded ARGs. Furthermore, we investigated the mechanisms underlying the promotive effect of disinfectants on transformation. We revealed that the addition of disinfectants significantly increased the membrane permeability and promoted membrane-related genes expression. Moreover, disinfectants led to the boosted bacterial respiration, ATP production and flagellum motility, as well as increased expression of bacterial secretion system-related genes. Together, our findings shed insights into the spread of ARGs through bacterial transformation and indicate potential risks associated with the widespread use of disinfectants. | 2023 | 36857920 |
| 34 | 9 | 0.9930 | Silencing of multiple target genes via ingestion of dsRNA and PMRi affects development and survival in Helicoverpa armigera. RNA interference (RNAi) triggered by exogenous double-stranded RNA (dsRNA) is a powerful tool to knockdown genetic targets crucial for the growth and development of agriculturally important insect pests. Helicoverpa armigera is a pest feeding on more than 30 economically important crops worldwide and a major threat. Resistance to insecticides and Bt toxins has been gradually increasing in the field. RNAi-mediated knockdown of H. armigera genes by producing dsRNAs homologous to genetic targets in bacteria and plants has a high potential for insect management to decrease agricultural loss. The acetylcholinesterase (AChE), ecdysone receptor (EcR) and v-ATPase-A (vAA) genes were selected as genetic targets. Fragments comprising a coding sequence of < 500 bp were cloned into the L4440 vector for dsRNA production in bacteria and in a TRV-VIGS vector in antisense orientation for transient expression of dsRNA in Solanum tuberosum leaves. After ingesting bacterial-expressed dsRNA, the mRNA levels of the target genes were significantly reduced, leading to mortality and abnormal development in larva of H. armigera. Furthermore, the S. tuberosum plants transformed with TRV-VIGS expressing AChE exhibited higher mortality > 68% than the control plants 17%, recorded ten days post-feeding and significant resistance in transgenic (transient) plants was observed. Moreover, larval lethality and molting defects were observed in larva fed on potato plants expressing dsRNA specific to EcR. Analysis of transcript levels by quantitative RT-PCR revealed that larval mortality was attributable to the knockdown of genetic targets by RNAi. The results demonstrated that down-regulation of H. armigera genes involved in ATP hydrolysis, transcriptional stimulation of development genes and neural conduction has aptitude as a bioinsecticide to control H. armigera population sizes and therefore decreases crop loss. | 2022 | 35729318 |
| 8488 | 10 | 0.9930 | Antihistamine drug loratadine at environmentally relevant concentrations promotes conjugative transfer of antibiotic resistance genes: Coeffect of oxidative stress and ion transport. Due to the widespread use of loratadine (LOR) as an antihistamine, it is widely distributed in the environment as an emerging contaminant. However, its impact on the dissemination of antibiotic resistance genes (ARGs) remains unclear. This study investigated the effect of LOR on the conjugative transfer of ARGs and elucidated the potential mechanisms through transcriptome analysis. The results showed that LOR significantly promoted the frequency of conjugative transfer up to 1.5- to 8.6-fold higher compared with the control group. Exposure to LOR increased reactive oxidative species (ROS) and intracellular Ca(2+) concentrations, leading to the upregulation of expression of genes related to transmembrane transport and SOS response. Meanwhile, it stimulated the increase of cell membrane permeability. Moreover, LOR exposure could enhance H(+) efflux in donor bacteria, resulting in the decrease of intracellular pH and the elevation of transmembrane potential, which could induce the increase of ion transport, thereby promoting plasmid efflux from the cell membrane. Based on this, we inferred that LOR can induce an increase in ROS level and intracellular Ca(2+) concentrations, and promoted the efflux of intracellular H(+). This, in turn, triggered the intensification of various ion transport processes on the cell membrane, thereby increasing membrane permeability and accelerating plasmid efflux. Ultimately, the coeffect of oxidative stress response and ion transport promoted conjugative transfer. This study demonstrated that LOR significantly promotes plasmid-mediated conjugative transfer of ARGs, providing novel insights into the mechanisms underlying this process. | 2025 | 39919578 |
| 8623 | 11 | 0.9930 | Antidepressants promote the spread of antibiotic resistance via horizontally conjugative gene transfer. Antibiotic resistance is a global concern threatening public health. Horizontal gene transfer (HGT) between bacterial species contributes greatly to the dissemination of antibiotic resistance. Conjugation is one of the major HGT pathways responsible for the spread of antibiotic resistance genes (ARGs). Antidepressant drugs are commonly prescribed antipsychotics for major depressive disorders and are frequently detected in aquatic environments. However, little is known about how antidepressants stress bacteria and whether such effect can promote conjugation. Here, we report that commonly prescribed antidepressants, sertraline, duloxetine, fluoxetine, and bupropion, can promote the conjugative transfer of plasmid-borne multidrug resistance genes carried by environmentally and clinically relevant plasmids. Noteworthy, the transfer of plasmids across bacterial genera is significantly enhanced by antidepressants at clinically relevant concentrations. We also reveal the underlying mechanisms of enhanced conjugative transfer by employing flow cytometric analysis, genome-wide RNA sequencing and proteomic analysis. Antidepressants induce the production of reactive oxygen species and the SOS response, increase cell membrane permeability, and upregulate the expression of conjugation relevant genes. Given the contribution of HGT in the dissemination of ARGs, our findings highlight the importance of prudent prescription of antidepressants and to the potential connection between antidepressants and increasing antibiotic resistance. | 2022 | 36054646 |
| 3548 | 12 | 0.9930 | From flagellar assembly to DNA replication: CJSe's role in mitigating microbial antibiotic resistance genes. The emergence of Antibiotic Resistance Genes (ARGs) in Campylobacter jejuni (CJ) poses a severe threat to food safety and human health. However, the specific impact of CJ and its variants on ARGs and other related factors remains to be further elucidated. Herein, integrated metagenomic sequencing and co-occurrence network analysis approach were employed to investigate the impact of CJ and CJ incorporated with biogenic selenium (CJSe) on ARGs, flagellar assembly pathways, microbial communities, and DNA replication pathways in chicken manure. Compared to the Control (CON) and CJ groups, the CJSe group exhibited 2.4-fold increase selenium levels (P < 0.01) in chicken manure. Notable differences were also observed between the CJ and CJSe groups, with sequence results showing a CJ > CJSe > CON trend in total ARG copy numbers. Furthermore, the CJSe group showed 31.6 % fewer flagellar assembly genes compared to the CJ group. Additionally, compared to the CJ group, CJSe inhibited pathways such as basal body/hook (e.g., FliH, FliO, FliQ reduced by 25-52 %) and stator (MotB downregulated by 42.3 %), suppressing flagellar assembly. We also found that both CJ and CJSe influenced bacterial DNA replication pathways, with the former increasing ARG-carrying bacteria and the latter, under selenium-induced selective pressure, reducing ARG-carrying bacteria. Moreover, compared to the CJ group, the CJSe group showed a significantly lower 9.72 % copy number of total archaeal DNA replication genes. Furthermore, through intricate co-occurrence network analysis, we discovered the complex interplay between changes in ARGs and bacterial and archaeal DNA replication dynamics within the microbial community. These findings indicate that CJSe mitigates the threat posed by CJ and reduces ARG prevalence, while its dual functionality enables applications in biofortified crop production and soil remediation in selenium-deficient regions, thereby advancing circular economy systems. While the current study demonstrates CJSe's dual functionality under controlled conditions, future work will implement a dedicated ecological risk assessment framework encompassing Se speciation/leaching tests and non-target organism assays to confirm environmental safety under field-relevant scenarios. This approach aligns with sustainable strategies for food security and public health safeguarding. | 2025 | 41108960 |
| 6473 | 13 | 0.9930 | The potential implications of reclaimed wastewater reuse for irrigation on the agricultural environment: The knowns and unknowns of the fate of antibiotics and antibiotic resistant bacteria and resistance genes - A review. The use of reclaimed wastewater (RWW) for the irrigation of crops may result in the continuous exposure of the agricultural environment to antibiotics, antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs). In recent years, certain evidence indicate that antibiotics and resistance genes may become disseminated in agricultural soils as a result of the amendment with manure and biosolids and irrigation with RWW. Antibiotic residues and other contaminants may undergo sorption/desorption and transformation processes (both biotic and abiotic), and have the potential to affect the soil microbiota. Antibiotics found in the soil pore water (bioavailable fraction) as a result of RWW irrigation may be taken up by crop plants, bioaccumulate within plant tissues and subsequently enter the food webs; potentially resulting in detrimental public health implications. It can be also hypothesized that ARGs can spread among soil and plant-associated bacteria, a fact that may have serious human health implications. The majority of studies dealing with these environmental and social challenges related with the use of RWW for irrigation were conducted under laboratory or using, somehow, controlled conditions. This critical review discusses the state of the art on the fate of antibiotics, ARB and ARGs in agricultural environment where RWW is applied for irrigation. The implications associated with the uptake of antibiotics by plants (uptake mechanisms) and the potential risks to public health are highlighted. Additionally, knowledge gaps as well as challenges and opportunities are addressed, with the aim of boosting future research towards an enhanced understanding of the fate and implications of these contaminants of emerging concern in the agricultural environment. These are key issues in a world where the increasing water scarcity and the continuous appeal of circular economy demand answers for a long-term safe use of RWW for irrigation. | 2017 | 28689129 |
| 9008 | 14 | 0.9930 | Dissolvable alginate hydrogel-based biofilm microreactors for antibiotic susceptibility assays. Biofilms are found in many infections in the forms of surface-adhering aggregates on medical devices, small clumps in tissues, or even in synovial fluid. Although antibiotic resistance genes are studied and monitored in the clinic, the structural and phenotypic changes that take place in biofilms can also lead to significant changes in how bacteria respond to antibiotics. Therefore, it is important to better understand the relationship between biofilm phenotypes and resistance and develop approaches that are compatible with clinical testing. Current methods for studying antimicrobial susceptibility are mostly planktonic or planar biofilm reactors. In this work, we develop a new type of biofilm reactor-three-dimensional (3D) microreactors-to recreate biofilms in a microenvironment that better mimics those in vivo where bacteria tend to form surface-independent biofilms in living tissues. The microreactors are formed on microplates, treated with antibiotics of 1000 times of the corresponding minimal inhibitory concentrations (1000 × MIC), and monitored spectroscopically with a microplate reader in a high-throughput manner. The hydrogels are dissolvable on demand without the need for manual scraping, thus enabling measurements of phenotypic changes. Bacteria inside the biofilm microreactors are found to survive exposure to 1000 × MIC of antibiotics, and subsequent comparison with plating results reveals no antibiotic resistance-associated phenotypes. The presented microreactor offers an attractive platform to study the tolerance and antibiotic resistance of surface-independent biofilms such as those found in tissues. | 2023 | 36691521 |
| 6774 | 15 | 0.9930 | Both silver ions and silver nanoparticles facilitate the horizontal transfer of plasmid-mediated antibiotic resistance genes. Antibiotic resistance in bacteria is a growing threat to global human health. Horizontal gene transfer (HGT) of antibiotic resistance genes (ARGs) is recognized as the primary contributor to antibiotic resistance dissemination. Silver nanoparticles (AgNPs) are widely used in personal care products as antimicrobial agents. While heavy metals are known to induce antibiotic resistance in bacteria, it is not known whether AgNPs in the environment can stimulate the HGT of ARGs. Here, we report that both AgNPs and ionic silver Ag(+), at environmentally relevant and sub-lethal concentrations, facilitate the conjugative transfer of plasmid-borne ARGs across bacterial genera (from the donor Escherichia coli K-12 LE392 to the recipient Pseudomonas putida KT2440). The underlying mechanisms of the Ag(+)- or AgNPs-promoted HGT were unveiled by detecting oxidative stress and cell membrane permeability, combined with genome-wide RNA sequencing and proteomic analyses. It was found that both Ag(+) and AgNPs exposure induced various bacterial responses that included reactive oxygen species (ROS) generation, membrane damage and the SOS response. This study exposes the potential ecological risks of environmental levels of AgNPs and Ag(+) for promoting the spread of ARGs and highlights concerns regarding the management of nanoparticles and heavy metals. | 2020 | 31783256 |
| 6580 | 16 | 0.9929 | Transmission of antimicrobial resistance (AMR) during animal transport. The transmission of antimicrobial resistance (AMR) between food-producing animals (poultry, cattle and pigs) during short journeys (< 8 h) and long journeys (> 8 h) directed to other farms or to the slaughterhouse lairage (directly or with intermediate stops at assembly centres or control posts, mainly transported by road) was assessed. Among the identified risk factors contributing to the probability of transmission of antimicrobial-resistant bacteria (ARB) and antimicrobial resistance genes (ARGs), the ones considered more important are the resistance status (presence of ARB/ARGs) of the animals pre-transport, increased faecal shedding, hygiene of the areas and vehicles, exposure to other animals carrying and/or shedding ARB/ARGs (especially between animals of different AMR loads and/or ARB/ARG types), exposure to contaminated lairage areas and duration of transport. There are nevertheless no data whereby differences between journeys shorter or longer than 8 h can be assessed. Strategies that would reduce the probability of AMR transmission, for all animal categories include minimising the duration of transport, proper cleaning and disinfection, appropriate transport planning, organising the transport in relation to AMR criteria (transport logistics), improving animal health and welfare and/or biosecurity immediately prior to and during transport, ensuring the thermal comfort of the animals and animal segregation. Most of the aforementioned measures have similar validity if applied at lairage, assembly centres and control posts. Data gaps relating to the risk factors and the effectiveness of mitigation measures have been identified, with consequent research needs in both the short and longer term listed. Quantification of the impact of animal transportation compared to the contribution of other stages of the food-production chain, and the interplay of duration with all risk factors on the transmission of ARB/ARGs during transport and journey breaks, were identified as urgent research needs. | 2022 | 36304831 |
| 6419 | 17 | 0.9929 | Can microplastics and disinfectant resistance genes pose conceivable threats to water disinfection process? Microplastic pollution in the environment has aroused widespread concerns, however, the potential environmental risks caused by excessive use of disinfectants are still unknown. Disinfectants with doses below the threshold can enhance the communication of resistance genes in pathogenic microorganisms, promoting the development and spread of antimicrobial activity. Problematically, the intensification of microplastic pollution and the increase of disinfectant consumption will become a key driving force for the growth of disinfectant resistance bacteria (DRB) and disinfectant resistance genes (DRGs) in the environment. Disinfection plays a crucial role in ensuring water safety, however, the presence of microplastics and DRGs seriously disturb the water disinfection process. Microplastics can reduce the concentration of disinfectant in the local environment around microorganisms and improve their tolerance. Microorganisms can improve their resistance to disinfectants or generate resistance genes via phenotypic adaptation, gene mutations, and horizontal gene transfer. However, very limited information is available on the impact of DRB and DRGs on disinfection process. In this paper, the contribution of microplastics to the migration and transmission of DRGs was analyzed. The challenges posed by the presence of microplastics and DRGs on conventional disinfection were thoroughly discussed. The knowledge gaps faced by relevant current research and further research priorities have been proposed in order to provide a scientific basis in the future. | 2023 | 37730038 |
| 8726 | 18 | 0.9929 | CRISPR-dCpf1 mediated whole genome crRNA inhibition library for high-throughput screening of growth characteristic genes in Bacillus amyloliquefaciens LB1ba02. Bacillus amyloliquefaciens LB1ba02 is generally recognized as food safe (GRAS) microbial host and important enzyme-producing strain in the industry. However, autolysis affects the growth of bacteria, further affecting the yield of target products. Besides, the restriction-modification system, existed in B. amyloliquefaciens LB1ba02, results in a low transformation efficiency, which further leads to a lack of high-throughput screening tools. Here, we constructed a genome-wide crRNA inhibition library based on the CRISPR/dCpf1 system and high-throughput screening of related genes affecting the cell growth and autolysis using flow cytometry in B. amyloliquefaciens LB1ba02. The whole genome crRNA library was first validated for resistance to the toxic chemical 5-fluorouracil, and then used for validation of essential genes. In addition, seven gene loci (oppD, flil, tuaA, prmA, sigO, hslU, and GE03231) that affect the growth characteristics of LB1ba02 were screened. Among them, the Opp system had the greatest impact on growth. When the expression of operon oppA-oppB-oppC-oppD-oppF was inhibited, the cell growth difference was most significant. Inhibition of other sites could also promote rapid growth of bacteria to varying degrees; however, inhibition of GE03231 site accelerated cell autolysis. Therefore, the whole genome crRNA inhibition library is well suited for B. amyloliquefaciens LB1ba02 and can be further applied to high-throughput mining of other functional genes. | 2023 | 37802457 |
| 9602 | 19 | 0.9929 | Polyhexamethylene biguanide promotes adaptive cross-resistance to gentamicin in Escherichia coli biofilms. Antimicrobial resistance is a critical public health issue that requires a thorough understanding of the factors that influence the selection and spread of antibiotic-resistant bacteria. Biocides, which are widely used in cleaning and disinfection procedures in a variety of settings, may contribute to this resistance by inducing similar defense mechanisms in bacteria against both biocides and antibiotics. However, the strategies used by bacteria to adapt and develop cross-resistance remain poorly understood, particularly within biofilms -a widespread bacterial habitat that significantly influences bacterial tolerance and adaptive strategies. Using a combination of adaptive laboratory evolution experiments, genomic and RT-qPCR analyses, and biofilm structural characterization using confocal microscopy, we investigated in this study how Escherichia coli biofilms adapted after 28 days of exposure to three biocidal active substances and the effects on cross-resistance to antibiotics. Interestingly, polyhexamethylene biguanide (PHMB) exposure led to an increase of gentamicin resistance (GenR) phenotypes in biofilms formed by most of the seven E. coli strains tested. Nevertheless, most variants that emerged under biocidal conditions did not retain the GenR phenotype after removal of antimicrobial stress, suggesting a transient adaptation (adaptive resistance). The whole genome sequencing of variants with stable GenR phenotypes revealed recurrent mutations in genes associated with cellular respiration, including cytochrome oxidase (cydA, cyoC) and ATP synthase (atpG). RT-qPCR analysis revealed an induction of gene expression associated with biofilm matrix production (especially curli synthesis), stress responses, active and passive transport and cell respiration during PHMB exposure, providing insight into potential physiological responses associated with adaptive crossresistance. In addition, confocal laser scanning microscopy (CLSM) observations demonstrated a global effect of PHMB on biofilm architectures and compositions formed by most E. coli strains, with the appearance of dense cellular clusters after a 24h-exposure. In conclusion, our results showed that the PHMB exposure stimulated the emergence of an adaptive cross-resistance to gentamicin in biofilms, likely induced through the activation of physiological responses and biofilm structural modulations altering gradients and microenvironmental conditions in the biological edifice. | 2023 | 38149014 |