Development Of Antibiotic Resistance Research Articles

Veterinary Drug Residues in the Food Chain as an Emerging Public Health Threat: Sources, Analytical Methods, Health Impacts, and Preventive Measures

Veterinary medications are necessary for both contemporary animal husbandry and food production, but their residues can linger in foods obtained from animals and pose a dangerous human risk. In this review, we aim to highlight the sources, occurrence, human exposure pathways, and human health effects of drug residues in food-animal products. Following the usage of veterinary medications, pharmacologically active compounds known as drug residues can be found in food, the environment, or animals. They can cause major health concerns to people, including antibiotic resistance development, the development of cancer, teratogenic effects, hypersensitivity, and disruption of normal intestinal flora. Drug residues in animal products can originate from variety of sources, including water or food contamination, extra-label drug use, and ignoring drug withdrawal periods. This review also examines how humans can be exposed to drug residues through drinking water, food, air, and dust, and discusses various analytical techniques for identifying these residues in food. Furthermore, we suggest some potential solutions to prevent or reduce drug residues in animal products and human exposure pathways, such as implementing withdrawal periods, monitoring programs, education campaigns, and new technologies that are crucial for safeguarding public health. This review underscores the urgency of addressing veterinary drug residues as a significant and emerging public health threat, calling for collaborative efforts from researchers, policymakers, and industry stakeholders to develop sustainable solutions that ensure the safety of the global food supply chain.

The LexA-RecA* structure reveals a cryptic lock-and-key mechanism for SOS activation.

The bacterial SOS response plays a key role in adaptation to DNA damage, including genomic stress caused by antibiotics. SOS induction begins when activated RecA*, an oligomeric nucleoprotein filament that forms on single-stranded DNA, binds to and stimulates autoproteolysis of the repressor LexA. Here, we present the structure of the complete Escherichia coli SOS signal complex, constituting full-length LexA bound to RecA*. We uncover an extensive interface unexpectedly including the LexA DNA-binding domain, providing a new molecular rationale for ordered SOS gene induction. We further find that the interface involves three RecA subunits, with a single residue in the central engaged subunit acting as a molecular key, inserting into an allosteric binding pocket to induce LexA cleavage. Given the pro-mutagenic nature of SOS activation, our structural and mechanistic insights provide a foundation for developing new therapeutics to slow the evolution of antibiotic resistance.

Dry powder inhalation containing muco-inert ciprofloxacin and colistin co-loaded liposomes for pulmonary P. Aeruginosa biofilm eradication

Pseudomonas aeruginosa (PA), a predominant pathogen in lung infections, poses significant challenges due to its biofilm formation, which is the primary cause of chronic and recalcitrant pulmonary infections. Bacteria within these biofilms exhibit heightened resistance to antibiotics compared to their planktonic counterparts, and their secreted toxins exacerbate lung infections. Diverging from traditional antibacterial therapy for biofilm eradication, this study introduces a novel dry powder inhalation containing muco-inert ciprofloxacin and colistin co-encapsulated liposomes (Cipro-Col-Lips) prepared using ultrasonic spray freeze drying (USFD) technique. This USFD dry powder is designed to efficiently deliver muco-inert Cipro-Col-Lips to the lungs. Once deposited, the liposomes rapidly diffuse into the airway mucus, reaching the biofilm sites. The muco-inert Cipro-Col-Lips neutralize the biofilm-secreted toxins and simultaneously trigger the release of their therapeutic payload, exerting a synergistic antibiofilm effect. Our results demonstrated that the optimal USFD liposomal dry powder formulation exhibited satisfactory in vitro aerosol performance in terms of fine particle fraction (FPF) of 44.44 ± 0.78 %, mass median aerodynamic diameter (MMAD) of 4.27 ± 0.21 μm, and emitted dose (ED) of 99.31 ± 3.31 %. The muco-inert Cipro-Col-Lips effectively penetrate the airway mucus and accumulate at the biofilm site, neutralizing toxins and safeguarding lung cells. The triggered release of ciprofloxacin and colistin works synergistically to reduce the biofilm’s antibiotic resistance, impede the development of antibiotic resistance, and eliminate 99.99 % of biofilm-embedded bacteria, including persister bacteria. Using a PA-beads induced biofilm-associated lung infection mouse model, the in vivo efficacy of this liposomal dry powder aerosol was tested, and the results demonstrated that this liposomal dry powder aerosol achieved a 99.7 % reduction in bacterial colonization, and significantly mitigated inflammation and pulmonary fibrosis. The USFD dry powder inhalation containing muco-inert Cipro-Col-Lips emerges as a promising therapeutic strategy for treating PA biofilm-associated lung infections.

Narrow spectrum nano-antibiotic for selective removal of ARB from contaminated water: New insights into stimuli response based on cellular attachment, lysis, and excretion

Narrow spectrum nano-antibiotics are supposedly the future trouble-shooters to improve the efficacy of conventional antimicrobials for treatment of severe bacterial infections, remove contamination from water and diminish the development of antibiotic resistance. In this study, antimicrobial peptide functionalized boron-carbon-nitride nanosheets ((Ant)pep@BCN NSs) are developed that are a promising wastewater disinfector and antibiotic resistant bactericide agent. These nanosheets are developed for selective removal and effective inactivation of antibiotic resistant bacteria (ARB) from water in presence of two virulent bacteria. The (Ant)pep@BCN NSs provide reactive surface receptors specific to the ARB. They mimic muralytic enzymes to damage the cell membrane of ARB. These NSs demonstrate 3-fold higher antimicrobial efficiency against the targeted ARB compared to pristine BCN even at lower concentrations. To the best of our knowledge, this is the first time that functionalized BCN has been developed to remove ARB selectively from wastewater. Furthermore, the (Ant)pep@BCN selectively reduced the microbiological load and led to morphological changes in Gram negative ARB in a mixed bacterial inoculum. These ARBs excreted outer–inner membrane vesicles (OIMVs) of triangular shape as a stimuli response to (Ant)pep@BCN NSs. These novel antimicrobial peptide-NSs have potential to improve treatment efficacy against ARB infections and water contamination.

N-Acetyl Cysteine-Decorated Nitric Oxide-Releasing Interface for Biomedical Applications.

Biomedical devices are vulnerable to infections and biofilm formation, leading to extended hospital stays, high expenditure, and increased mortality. Infections are clinically treated via the administration of systemic antibiotics, leading to the development of antibiotic resistance. A multimechanistic strategy is needed to design an effective biomaterial with broad-spectrum antibacterial potential. Recent approaches have investigated the fabrication of innately antimicrobial biomedical device surfaces in the hope of making the antibiotic treatment obsolete. Herein, we report a novel fabrication strategy combining antibacterial nitric oxide (NO) with an antibiofilm agent N-acetyl cysteine (NAC) on a polyvinyl chloride surface using polycationic polyethylenimine (PEI) as a linker. The designed biomaterial could release NO for at least 7 days with minimal NO donor leaching under physiological conditions. The proposed surface technology significantly reduced the viability of Gram-negative Escherichia coli (>97%) and Gram-positive Staphylococcus aureus (>99%) bacteria in both adhered and planktonic forms in a 24 h antibacterial assay. The composites also exhibited a significant reduction in biomass and extra polymeric substance accumulation in a dynamic environment over 72 h. Overall, these results indicate that the proposed combination of the NO donor with mucolytic NAC on a polymer surface efficiently resists microbial adhesion and can be used to prevent device-associated biofilm formation.

Enhanced sensitivity of extracellular antibiotic resistance genes (ARGs) to environmental concentrations of antibiotic

As emerging contaminants, antibiotics are frequently present in various environments, particularly rivers, albeit often at sublethal concentrations (ng/L∼μg/L). Assessing the risk associated with these low levels, which are far below the lethal threshold for most organisms, remains challenging. In this study, using microcosms containing planktonic bacteria and biofilm, we examined how antibiotic resistance genes (ARGs) in different physical states, including intracellular ARGs (iARGs) and extracellular ARGs (eARGs) responded to these low-level antibiotics. Our findings reveal a positive correlation between sub-lethal antibiotic exposure (ranging from 0.1 to 10 μg/L) and increased prevalence (measured as ARG copies/16s rDNA) of both iARGs and eARGs in planktonic bacteria. Notably, eARGs demonstrated greater sensitivity to antibiotic exposure compared to iARGs, with a lower threshold (0.1 μg/L for eARGs versus 1 μg/L for iARGs) for abundance increase. Moreover, ARGs in biofilms demonstrates higher sensitivity to antibiotic exposure compared to planktonic bacteria. To elucidate the underlying mechanisms, we established an integrated population dynamics-pharmacokinetics-pharmacodynamics (PD-PP) model. This model indicates that the enhanced sensitivity of eARGs is primarily driven by an increased potential for plasmid release from cells under low antibiotic concentrations. Furthermore, the accumulation of antibiotic in biofilms induces a greater sensitivity of ARG compared to the planktonic bacteria. This study provides a fresh perspective on the development of antibiotic resistance and offers an innovative approach for assessing the risk of sublethal antibiotic in the environment.

Optimizing removal of antiretroviral drugs from tertiary wastewater using chlorination and AI-based prediction with response surface methodology

Chemical and pharmaceutical chemicals found in water sources create substantial risks to human health and the environment. The presence of pharmaceutical contaminants in water can cause antibiotic resistance development, toxicity to aquatic organisms, and endocrine disruption. Hence, the elimination of chemicals and other contaminants from wastewater prior to its release is a burgeoning concern in the domains of engineering and science. The use of treatment technologies in wastewater treatment plants can remove pharmaceutical contaminants through the oxidation process. However, many traditional wastewater treatment plants lack the advanced monitoring tools required to detect low concentrations of pharmaceuticals. Without the ability to detect these compounds, it's challenging to treat them effectively. The goal of this study was to use Response Surface Methodology (RSM) and Artificial Neural Networks (ANN) algorithms to model and improve how Nevirapine and Efavirenz break down in different chlorination conditions. The RSM analysis revealed statistically significant models (F-values: Nevirapine, pH-t: 108.15, T-t: 76.55, ICC-t: 110.84), indicating a strong correlation between operational parameters (pH, temperature, and initial chlorine concentration) and degradation behavior. The ANN model accurately predicted the degradation of both Nevirapine and Efavirenz under various chlorination conditions, as confirmed by analyzing actual-predicted graphs, residual plots, and Mean Squared Error (MSE) values. The ANN model using ICC-t achieved the highest MOD value of 31.31 % for Nevirapine. The ANN model based on ICC-t yielded a maximum MOD value of 16.06 % for Efavirenz. These findings provide valuable insights into optimizing chlorination processes for better removal of these pharmaceutical contaminants from water.

Antibiotic dose and nutrient availability differentially drive the evolution of antibiotic resistance and persistence.

Effective treatment of bacterial infections proves increasingly challenging due to the emergence of bacterial variants that endure antibiotic exposure. Antibiotic resistance and persistence have been identified as two major bacterial survival mechanisms, and several studies have shown a rapid and strong selection of resistance or persistence mutants under repeated drug treatment. Yet, little is known about the impact of the environmental conditions on resistance and persistence evolution, and the potential interplay between both phenotypes. Based on the distinct growth and survival characteristics of resistance and persistence mutants, we hypothesized that the antibiotic dose and availability of nutrients during treatment might play a key role in the evolutionary adaptation to antibiotic stress. To test this hypothesis, we combined high-throughput experimental evolution with a mathematical model of bacterial evolution under intermittent antibiotic exposure. We show that high nutrient levels during antibiotic treatment promote selection of high-level resistance, but that resistance mainly emerges independently of persistence when the antibiotic concentration is sufficiently low. At higher doses, resistance evolution is facilitated by the preceding or concurrent selection of persistence mutants, which ensures survival of populations in harsh conditions. Collectively, our experimental data and mathematical model elucidate the evolutionary routes towards increased bacterial survival under different antibiotic treatment schedules, which is key to designing effective antibiotic therapies.

Emergent antibiotic persistence in a spatially structured synthetic microbial mutualism.

Antibiotic persistence (heterotolerance) allows a sub-population of bacteria to survive antibiotic-induced killing and contributes to the evolution of antibiotic resistance. Although bacteria typically live in microbial communities with complex ecological interactions, little is known about how microbial ecology affects antibiotic persistence. Here, we demonstrated within a synthetic two-species microbial mutualism of Escherichia coli and Salmonella enterica that the combination of cross-feeding and community spatial structure can emergently cause high antibiotic persistence in bacteria by increasing the cell-to-cell heterogeneity. Tracking ampicillin-induced death for bacteria on agar surfaces, we found that E. coli forms up to 55 times more antibiotic persisters in the cross-feeding coculture than in monoculture. This high persistence could not be explained solely by the presence of S. enterica, the presence of cross-feeding, average nutrient starvation, or spontaneous resistant mutations. Time-series fluorescent microscopy revealed increased cell-to-cell variation in E. coli lag time in the mutualistic co-culture. Furthermore, we discovered that an E. coli cell can survive antibiotic killing if the nearby S. enterica cells on which it relies die first. In conclusion, we showed that the high antibiotic persistence phenotype can be an emergent phenomenon caused by a combination of cross-feeding and spatial structure. Our work highlights the importance of considering spatially structured interactions during antibiotic treatment and understanding microbial community resilience more broadly.

Exploring the impact of silver-based nanomaterial feed additives on green algae through single-cell techniques

Silver in its various forms, including dissolved silver ions (Ag+) and silver nanoparticles (AgNPs), is a promising alternative to traditional antibiotics, largely used in livestock as feed additives and could contribute to the decrease and avoidance of the development of antibiotic resistance. The present study aims to assess the potential ecotoxicity of a silver-based nanomaterial (Ag-kaolin), the feed supplemented with the nanomaterial and the faeces since the latter are the ones that finally reach the environment. To this end, green alga Raphidocellis subcapitata was exposed to the extracts of Ag-kaolin, supplemented feed, and pig faeces for 72 h, along with Ag+ and AgNPs as controls for comparison purposes. Given the complexity of the studied materials, single-cell techniques were used to follow the changes in the cell numbers and chlorophyll fluorescence by flow cytometry (FCM), and the accumulation of silver in the exposed cells by single cell inductively coupled plasma mass spectrometry (SC-ICP-MS). Changes in cell morphology were observed by cell imaging multimode reader. The results revealed a decrease in chlorophyll fluorescence, even at low concentrations of Ag-kaolin (10 μg L−1) after 48 h of exposure. Additionally, complete growth inhibition was found with this material like the results obtained by exposure to Ag+. For the supplemented feed, a concentration of 50 μg L−1 was necessary to achieve complete growth inhibition. However, the behaviour differed for the leachate of faeces, which released Ag2S and AgCl alongside Ag+ and AgNPs. At 50 μg L−1, inhibition was minimal, primarily due to the predominance of less toxic Ag2S in the leachate. The uptake of silver by the cells was confirmed with all the samples through SC-ICP-MS analysis. These findings demonstrate that the use of Ag-kaolin as a feed supplement will lead to a low environmental impact.

Intestinal Microbiome and Antimicrobial Resistivity: A Study in Recent Times

The world has recently witnessed a pandemic and is now challenged by continuous environmental changes. Human health is in constant jeopardy with the rise in bacterial, fungal, and viral infections. Antibiotics are the most widely used medication for the treatment of any infection. The urban population does not always maintain a healthy lifestyle due to the fast-paced nature of life. West Bengal the eastern state of India is no exception to this directive. Rampant use of antibiotics and their frequent consumption has widely increased over the years. This is posing a serious threat to the healthy microbiome of the human intestine. It is resulting in a decline of the healthy microbiota and the development of antibiotic resistance. The study aims to understand the effect of antibiotic consumption in the post-COVID scenario on the gut microbiome of the West Bengal population. The population includes both rural and urban as it takes into account the different lifestyles.

A Sublethal Concentration of Chlorine Induces Antibiotic Resistance in Salmonella via Production of Reactive Oxygen Species

Studies have shown that the production of reactive oxygen species (ROS) is triggered by bactericidal antibiotics, which contributes significantly to the killing of bacterial cells and increasing mutations in surviving cells. In this study, we hypothesized that exposure of Salmonella to sublethal concentrations of hypochlorite (NaOCl), a commonly used sanitizer in household and food industries increases mutation rates, leading to the development of antibiotic resistance. We found that a sublethal concentration (20 ppm) of NaOCl increased the mutation rates of S. typhimurium 14028s significantly (p < 0.05), which was prevented by the ROS scavenger thiourea, supporting that the increased mutation was due to NaOCl-triggered ROS production. We further found that the exposure of S. typhimurium 14028s to the same sublethal concentration of NaOCl increases resistance to kanamycin among the 3 antibiotics evaluated. The results of this study suggest that when NaOCl applied as a sanitizer fails to kill Salmonella due to diluted local concentrations or presence of organic materials, it can cause an adverse outcome of developing antibiotic resistance of the pathogen.

Rapid, sensitive, and user-friendly detection of Pseudomonas aeruginosa using the RPA/CRISPR/Cas12a system.

Pseudomonas aeruginosa (P. aeruginosa) is a life-threatening bacterium known for its rapid development of antibiotic resistance, posing significant challenges in clinical treatment, biosecurity, food safety, and environmental monitoring. Early and accurate identification of P. aeruginosa is crucial for effective intervention. The lasB gene of P. aeruginosa was selected as the target for the detection. RPA primers for recombinase polymerase amplification (RPA) and crRNA for CRISPR/Cas12a detection were meticulously designed to target specific regions within the lasB gene. The specificity of the RPA/CRISPR/Cas12a detection platform was assessed using 15 strains. The detection limit of RPA/CRISPR/Cas12a detection platform was determined by utilizing a pseudo-dilution series of the P. aeruginosa DNA. The practical applicability of the RPA/CRISPR/Cas12a detection platform was validated by comparing it with qPCR on 150 samples (35 processed meat product samples, 55 cold seasoned vegetable dishes, 60 bottled water samples). The RPA/CRISPR/Cas12a detection platform demonstrates high specificity, with no cross-reactivity with non-P. aeruginosa strains. This assay exhibits remarkable sensitivity, with a limit of detection (LOD) of 100 copies/µL for fluorescence assay and 101 copies/µL for the LFTS method. Furthermore, the performance of the RPA/CRISPR/Cas12a detection platform is comparable to that of the well-established qPCR method, while offering advantages such as shorter reaction time, simplified operation, and reduced equipment requirements. The RPA/CRISPR/Cas12a detection platform presents a straightforward, accurate, and sensitive approach for early P. aeruginosa detection and holds great promise for diverse applications requiring rapid and reliable identification.

Microbial-mediated conversion of soil organic carbon co-regulates the evolution of antibiotic resistance

The influence of organic carbon on the proliferation of antibiotic resistance genes (ARGs) in the soil has been widely documented. However, it is unclear how soil organic carbon (SOC) interacts with the evolution of antibiotic resistance in bacteria. Here, we examined the variations in ARGs abundance during SOC mineralization and explored the microbiological mechanisms and key metabolic pathways involved in their coevolution. The results showed that the SOC mineralization rate was closely correlated with ARGs abundance (p < 0.05). High organic carbon (OC) mineralization was conducive to the occurrence of multidrug resistance genes. For example, multidrug_transporter and mexB increased 2.26 and 7.83 times from the initial level. The competitor (stress) evolutionary strategy model revealed that higher OC inputs drive environmental microorganisms to evolve from stress tolerant to high resistance and strong adaptation. Meta-genomic and transcriptomic analyses revealed that the conversion process of pyruvate to acetyl-CoA to acetate was the critical metabolic pathway for the co-regulation of antibiotic resistance. Gene deletion validation trials have demonstrated that the key functional genes (ackA and pta) involved in this process can modulate the development of vancomycin and multidrug resistance. This outcome provides a preliminary framework for microbial mechanisms that target the co-regulation of microbial OC conversion and the evolution of antibiotic resistance.

Molecular drilling to combat salmonella typhi biofilm using L-Asparaginase via multiple targeting process

ABSTRACT Objectives Salmonella Typhibiofilm condition is showing as a major public health problem due to the development of antibiotic resistance and less available druggable target proteins. Therefore, we aimed to identify some more druggable targets of S. Typhibiofilm using computational drilling at the genome/proteome level so that the target shortage problem could be overcome and more antibiofilm agents could be designed in the future against the disease. Methods We performed protein–protein docking and interaction analysis between the homological identified target proteins of S.Typhi biofilm and a therapeutic protein L-Asparaginase. Results We have identified some druggable targets CsgD, BcsA, OmpR, CsgG, CsgE, and CsgF in S.Typhi. These targets showed high-binding affinity BcsA (−219.8 Kcal/mol) >csgF (−146.52 Kcal/mol) >ompR (−135.68 Kcal/mol) >CsgE (−134.66 Kcal/mol) >CsgG (−113.81 Kcal/mol) >CsgD(−95.39 Kcal/mol) with therapeutic enzyme L-Asparaginase through various hydrogen-bonds and salt-bridge. We found six proteins of S. Typhi biofilm from the Csg family as druggable multiple targets. Conclusion This study provides insight into the idea of identification of new druggable targets and their multiple targeting with L-Asparaginase to overcome target shortage in S. Typhibiofilm-mediated infections. Results further indicated that L-Asparaginase could potentially be utilized as an antibiofilm biotherapeutic agent against S.Typhi.

Chitosan-based hydrogel incorporating mesoporous silica/zinc oxide nanoparticles with controlled swelling and potent antibacterial activity

Staphylococcus aureus (S. aureus) is a notable causative agent of bacterial infections known for its development of antibiotic resistance over time. In response, hydrogels augmented with antibacterial nanoparticles (NPs) and controllable swelling properties have emerged as promising alternatives. In the study, a novel chitosan (CS)-based hydrogel was prepared by combining CS as a main component, zinc oxide NPs (ZnO NPs) as an antibacterial agent, and mesoporous silica NPs (MSN) as the swelling control material. Comprehensive characterization of the prepared novel hydrogels were carried out by dynamic light scattering (DLS), zeta potential (ζ-potential), Brunauer–Emmett–Teller (BET) analysis, Fourier-transform infrared spectroscopy (FTIR), scanning electron microcopy (SEM), and X-ray diffraction (XRD). The ZnO/MSN/CS-based hydrogel exhibited superior swelling, precisely controllable swelling, and potent antibacterial activity against S. aureus. These hybrid CS-based hydrogels, incorporating both ZnO NPs and MSN, exhibit significant potential as agents for combating antibiotic resistance, offering an alternative strategy to mitigate reliance on conventional antibiotics.

Climate warming promotes collateral antibiotic resistance development in cyanobacteria

Both cyanobacterial blooms and antibiotic resistance have aggravated worldwide and posed a great threat to public health in recent years. As a significant source and reservoir of water environmental resistome, cyanobacteria exhibit confusing discrepancy between their reduced susceptibility and their chronic exposure to antibiotic mixtures at sub-inhibitory concentrations. How the increasing temperature affects the adaptive evolution of cyanobacteria-associated antibiotic resistance in response to low-level antibiotic combinations under climate change remains unclear. Here we profiled the antibiotic interaction and collateral susceptibility networks among 33 commonly detected antibiotics in 600 cyanobacterial strains isolated from 50 sites across four eutrophicated lakes in China. Cyanobacteria-associated antibiotic resistance level was found positively correlated to antibiotic heterogeneity across all sites. Among 528 antibiotic combinations, antagonism was observed for 62 % interactions and highly conserved within cyanobacterial species. Collateral resistance was detected in 78.5 % of pairwise antibiotic interaction, leading to a widened or shifted upwards mutant selection window for increased opportunity of acquiring second-step mutations. We quantified the interactive promoting effect of collateral resistance and increasing temperature on the evolution of both phenotypic and genotypic cyanobacteria-associated resistance under chronic exposure to environmental level of antibiotic combinations. With temperature increasing from 16 °C to 36 °C, the evolvability index and genotypic resistance level increased by 1.25 – 2.5 folds and 3 – 295 folds in the collateral-resistance-informed lineages, respectively. Emergence of resistance mutation pioneered by tolerance, which was jointly driven by mutation rate and persister fraction, was found to be accelerated by increased temperature and antibiotic switching rate. Our findings provided mechanic insights into the boosting effect of climate warming on the emergence and development of cyanobacteria-associated resistance against collateral antibiotic phenotypes.

Tebuconazole promotes spread of a multidrug-resistant plasmid into soil bacteria to form new resistant bacterial strains

The development of antibiotic resistance threatens human and environmental health. Non-antibiotic stressors, including fungicides, may contribute to the spread of antibiotic resistance genes (ARGs). We determined the promoting effects of tebuconazole on ARG dissemination using a donor, Escherichia coli MG1655, containing a multidrug-resistant fluorescent plasmid (RP4) and a recipient (E. coli HB101). The donor was then incorporated into the soil to test whether tebuconazole could accelerate the spread of RP4 into indigenous bacteria. Tebuconazole promoted the transfer of the RP4 plasmid from the donor into the recipient via overproduction of reactive oxygen species (ROS), enhancement of cell membrane permeability and regulation of related genes. The dissemination of the RP4 plasmid from the donor to soil bacteria was significantly enhanced by tebuconazole. RP4 plasmid could be propagated into more genera of bacteria in tebuconazole-contaminated soil as the exposure time increased. These findings demonstrate that the fungicide tebuconazole promotes the spread of the RP4 plasmid into indigenous soil bacteria, revealing the potential risk of tebuconazole residues enhancing the dissemination of ARGs in soil environments.

Detergent Chemistry Modulates the Transgression of Planetary Boundaries including Antimicrobial Resistance and Drug Discovery.

Detergent chemistry enables applications in the world today while harming safe operating spaces that humanity needs for survival. Aim of this review is to support a holistic thought process in the design of detergent chemistry. We harness the planetary boundary concept as a framework for literature survey to identify progresses and knowledge gaps in context with detergent chemistry and five planetary boundaries that are currently transgressed, i.e., climate, freshwater, land system, novel entities, biosphere integrity. Our survey unveils the status of three critical challenges to be addressed in the years to come, including (i) the implementation of a holistically, climate-friendly detergent industry; (ii) the alignment of materialistic and social aspects in creating technical solutions by means of sustainable chemistry; (iii) the development of detergents that serve the purpose of applications but do not harm the biosphere in their role as novel entities. Specifically, medically relevant case reports revealed that even the most sophisticated detergent design cannot sufficiently accelerate drug discovery to outperform the antibiotic resistance development that detergents simultaneously promote as novel entities. Safe operating spaces that humanity needs for its survival may be secured by directing future efforts beyond sustainable chemistry, resource efficiency, and net zero emission targets.

Detergent Chemistry Modulates the Transgression of Planetary Boundaries including Antimicrobial Resistance and Drug Discovery

Detergent chemistry enables applications in the world today while harming safe operating spaces that humanity needs for survival. Aim of this review is to support a holistic thought process in the design of detergent chemistry. We harness the planetary boundary concept as a framework for literature survey to identify progresses and knowledge gaps in context with detergent chemistry and five planetary boundaries that are currently transgressed, i.e., climate, freshwater, land system, novel entities, biosphere integrity. Our survey unveils the status of three critical challenges to be addressed in the years to come, including (i) the implementation of a holistically, climate‐friendly detergent industry; (ii) the alignment of materialistic and social aspects in creating technical solutions by means of sustainable chemistry; (iii) the development of detergents that serve the purpose of applications but do not harm the biosphere in their role as novel entities. Specifically, medically relevant case reports revealed that even the most sophisticated detergent design cannot sufficiently accelerate drug discovery to outperform the antibiotic resistance development that detergents simultaneously promote as novel entities. Safe operating spaces that humanity needs for its survival may be secured by directing future efforts beyond sustainable chemistry, resource efficiency, and net zero emission targets.