Low Concentrations Of Antibiotics Research Articles

Fine particulate matter as a key factor promoting the spread of antibiotics in river network

The extensive utilization of antibiotics has resulted in their frequent detection, contributing to an increased abundance of antibiotic resistance genes in rivers and posing a significant threat to environmental health. Particulate matter plays a crucial role as the primary carrier of various pollutants in river ecosystem. Its physicochemical properties and processes of sedimentation and re-suspension can influence the migration and transformation of antibiotics, yet the mechanisms of this impact remain unclear. In this study, we investigated the distribution characteristics at the micro-scale of particles in the upstream plain river network of the Taihu basin and the adsorption behaviors of antibiotics in particulate matter. The results revealed that particles were predominantly in the size range of 30 to 150 μm in the river network and highest total antibiotic concentrations in 0 to 10 μm particle size fractions. Adsorption experiments also confirmed that the smaller the suspended particle size, the stronger the adsorption capacity for antibiotics. Spatially, both the average particle size and total antibiotic concentrations were lower downstream than upstream. The distribution mechanism of antibiotic in river network sediments was significantly influenced by frequent resuspension and settling of fine particles with a stronger capacity to adsorb antibiotics under hydrodynamic conditions. This ultimately facilitated the release of antibiotics from sediment into the water, resulting in lower antibiotic concentrations in downstream sediments relative to upstream These findings suggest that fine particles serve as the primary carriers of antibiotics, and their sorting and transport processes can significantly influence the distribution of antibiotics in water-sediment systems. This study enhances our understanding of the migration mechanisms of antibiotics in river networks and will prove beneficial for the development of management strategies aimed at controlling antibiotic dissemination.

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.

Triterpenoid saponin from Panax ginseng increases the sensitivity of methicillin-resistant Staphylococcus aureus to β-lactam and aminoglycoside antibiotics.

The triterpenoid saponins, ginsenosides, are the major bioactive compound of red ginseng and can exert various physiological activities. In the present study, we examined whether red ginseng extract (RGE) exerts antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). RGE had no bactericidal activity, at least in the range of dissolvable concentration. However, RGE reduced 0.03-0.25-fold the minimum inhibitory concentration (MIC) values of β-lactam antibiotics (oxacillin, ampicillin, carbenicillin, and cefazolin) and aminoglycoside antibiotics (kanamycin and gentamicin) against the two laboratory strains of MRSA. Moreover, the fractional inhibitory concentration index indicated the synergistic activity of RGE with each of the antibiotics. RGE also increased the kanamycin sensitivity of 15 MRSA strains isolated from human volunteers and increased the ampicillin sensitivity of five MRSA strains isolated from dairy cows diagnosed with bovine mastitis. In contrast, RGE did not alter the MIC values of fosfomycin, tetracycline, and erythromycin, suggesting that RGE acts selectively. In contrast, Triton X-100, which was reported to reduce the MIC value of β-lactam antibiotics to MRSA by increasing membrane permeability, reduced the MIC values of fosfomycin and tetracycline. These results indicate that RGE increases the bactericidal effect of antibiotics via a mechanism different from that used by Triton X-100. We found that ginsenoside Rg3 (Rg3), a component of RGE, was an essential compound that exhibits synergy activity with antibiotics. Furthermore, the non-natural compound K, which contains a common protopanaxadiol aglycon moiety with Rg3, also showed synergistic activity with antibiotics. Thus, Rg3 and compound K are potentially new antibiotic adjuvants against MRSA.IMPORTANCEMethicillin-resistant Staphylococcus aureus (MRSA) is a multidrug-resistant organism that is prevalent worldwide. Therefore, the research and development of new agents against MRSA are required. We first found that ginsenoside Rg3 (Rg3) in red ginseng, made from the roots of Panax ginseng C. A. Meyer, increased the sensitivity of β-lactam antibiotics and aminoglycoside antibiotics to MRSA. Furthermore, we identified that compound K, an unnatural ginsenoside analog, also increased the sensitivity of antibiotics to MRSA, similar to Rg3. By contrast, neither Rg3 nor compound K increased the sensitivity of fosfomycin, tetracycline, and erythromycin to MRSA, suggesting that these act selectively. In the present study, the natural compound Rg3 and its structural isomer, compound K, are potentially new antibiotic adjuvants against MRSA. Currently, multiple antibiotics are used to treat MRSA, but the use of these adjuvants is expected to enable the treatment of MRSA with a single antibiotic and low concentrations of antibiotics.

The presence of antibiotic-resistant bacteria at four Norwegian wastewater treatment plants: seasonal and wastewater-source effects

Wastewater treatment plants receive low concentrations of antibiotics. Residual concentrations of antibiotics in the effluent may accelerate the development of antibiotic resistance in the receiving environments. Monitoring of antimicrobial resistance genes (ARGs) in countries with strict regulation of antibiotic use is important in gaining knowledge of how effective these policies are in preventing the emergence of ARGs or whether other strategies are required, for example, at-source treatment of hospital effluents. This study evaluates the presence of certain common resistance genes (blaSHV-1, blaTEM-1, msrA, ermA, ermC, tetM, tetL, tetA, vanA, and vanC) in the influent, sludge, and effluent of four wastewater treatment plants (WWTPs) in the North Jæren region of Norway at two different sampling times (January and May). These WWTPs vary in drainage area and wastewater composition and were selected based on their differing wastewater characteristics. Randomly selected colonies from the activated sludge samples were used to determine the minimum inhibitory concentration (MIC) for ampicillin, vancomycin, and tetracycline. In addition, variations in the bacterial composition of the wastewater were characterized via 16S rRNA sequencing and were analyzed in terms of bacterial host taxa that explain the presence of the ARGs in wastewater. The MIC tests revealed MIC90 values of >128 µg/mL for ampicillin, ≥128 µg/mL for vancomycin, and 32 µg/mL for tetracycline. In addition, the three resistance genes, ermB, tetA, and tetM, that were present in the influent and activated sludge were still present in the effluent. These results indicate that WWTPs represent a direct route into the environment for resistance genes and do not significantly reduce their abundance. Hence, the development of treatment methods for the removal of these genes from WWTPs in the future is of utmost importance.

Efficient production and characterization of a newly identified trehalase for inhibiting the formation of bacterial biofilms

Trehalase has attracted widespread attention in medicine, agriculture, food, and ethanol industry due to its ability to specifically degrade trehalose. Efficient expression of trehalase remains a challenge. In this study, a putative trehalase-encoding gene (Tre-zm) from Zunongwangia mangrovi was explored using gene-mining strategy and heterologously expressed in E. coli. Trehalase activity reached 3374 U·mL−1 after fermentation optimization. The scale-up fermentation in a 15 L fermenter was achieved with a trehalase production of 15,068 U·mL−1. The recombinant trehalase TreZM was purified and characterized. It displayed optimal activity at 35 °C and pH 8.5, with Mn2+, Sn2+, Na+, and Fe2+ promoting the activity. Notably, TreZM showed significant inhibition effect on biofilm forming of Staphylococcus epidermidis. The combination of TreZM with a low concentration of antibiotics could inhibit 70 % biofilm formation of Staphylococcus epidermidis and 28 % of Pseudomonas aeruginosa. Hence, this study provides a promising candidate for industrial production of trehalase and highlights its potential application to control harmful biofilms.

Efflux-mediated Multidrug Resistance in Critical Gram-negative Bacteria and Natural Efflux Pump Inhibitors.

Multidrug Resistance mechanisms in microorganisms confer the slackness of the existing drugs, leading to added difficulty in treating infections. As a consequence, efficient novel drugs and innovative therapies to treat MDR infections are necessarily required. One of the primary contributors to the emergence of multidrug resistance in gram-negative bacteria has been identified as the efflux pumps. These transporter efflux pumps reduce the intracellular concentration of antibiotics and aid bacterial survival in suboptimal low antibiotic concentration environments that may cause treatment failure. The reversal of this resistance via inhibition of the efflux mechanism is a promising method for increasing the effectiveness of antibiotics against multidrug-resistant pathogens. Such EPI, in combination with antibiotics, can make it easier to reintroduce traditional antibiotics into clinical practice. This review mostly examines efflux-mediated multidrug resistance in critical gram-negative bacterial pathogens and EPI of plant origin that have been reported over previous decades.

Resistance mechanism of Escherichia coli strains with different ampicillin resistance levels.

Antibiotic resistance is an important problem that threatens medical treatment. Differences in the resistance levels of microorganisms cause great difficulties in understanding the mechanisms of antibiotic resistance. Therefore, the molecular reasons underlying the differences in the level of antibiotic resistance need to be clarified. For this purpose, genomic and transcriptomic analyses were performed on three Escherichia coli strains with varying degrees of adaptive resistance to ampicillin. Whole-genome sequencing of strains with different levels of resistance detected five mutations in strains with 10-fold resistance and two additional mutations in strains with 95-fold resistance. Overall, three of the seven mutations occurred as a single base change, while the other four occurred as insertions or deletions. While it was thought that 10-fold resistance was achieved by the effect of mutations in the ftsI, marAR, and rpoC genes, it was found that 95-fold resistance was achieved by the synergistic effect of five mutations and the ampC mutation. In addition, when the general transcriptomic profiles were examined, it was found that similar transcriptomic responses were elicited in strains with different levels of resistance. This study will improve our view of resistance mechanisms in bacteria with different levels of resistance and provide the basis for our understanding of the molecular mechanism of antibiotic resistance in ampicillin-resistant E. coli strains. KEY POINTS: •The mutation of the ampC promoter may act synergistically with other mutations and lead to higher resistance. •Similar transcriptomic responses to ampicillin are induced in strains with different levels of resistance. •Low antibiotic concentrations are the steps that allow rapid achievement of high antibiotic resistance.

Co-exposure of chromium or cadmium and a low concentration of amoxicillin are responsible to emerge amoxicillin resistant Staphylococcus aureus

Heavy metals and antimicrobials co-exist in many environmental settings. The co-exposure of heavy metals and antimicrobials can drive emergence of antimicrobial resistant (AMR) Enterobacteriaceae. We hypothesized that co-exposure to heavy metals and a low concentration of antibiotic might alter antimicrobial susceptibility patterns, which facilitate emergence of AMR Staphylococcus aureus. The growth kinetics of antimicrobial susceptibleS. aureuswas carried out in the presence of chromium or cadmium salt and a low concentration of antibiotics. Subsequently, the antimicrobial susceptibility pattern was determined by the Kirby-Bauer disc diffusion method.Moreover, the mRNA copy number was determined by reverse transcription polymerase chain reaction. The antimicrobial susceptibility profile revealed that the zone of inhibition (ZOI) for ampicillin, amoxicillin, ciprofloxacin and doxycycline was significantly decreased in chromium pre-exposed S. aureuscompared to unexposed bacteria, whereas cadmium pre-exposed bacteria only showed significant decreased in ZOI for amoxicillin. Moreover, the MIC of amoxicillin for S. aureus was increased by 8-fold in chromium and 32-fold in cadmium when bacteria were co-exposed with low concentrations of amoxicillin. The mRNA expression of femX, mepA and norA also significantly increased in S. aureus after exposure tochromium and a low concentration of amoxicillin. Cultivation of S. aureus at the minimum levels of chromium or cadmium and a low concentration of amoxicillin increased the inhibitory concentration of amoxicillin through inducing bacterial efflux pumps and antibiotic resistant genes. However, it is warranted to assess the whole transcriptome to find out all responsible factors behind this de novo amoxicillin resistant S. aureus.

A Liquid Chromatography-Tandem Mass Spectrometry Method for Simultaneously Determining Meropenem and Linezolid in Blood and Cerebrospinal Fluid.

Antibiotic therapy requires appropriate dosage of drugs for effective treatment. Too low antibiotic concentrations may lead to treatment failure and the development of resistant pathogens, whereas overdosing may cause neurological side effects or hemolytic diseases. Meropenem and linezolid are used only in the treatment of serious infections or when other antibiotics are no longer effective as well as for treating central nervous system infections. It is difficult or sometimes even impossible to predict the relation between dosing of antibiotics and its cerebrospinal fluid (CSF) concentration; thus, a method of determining antibiotics not only in the blood but also in the CSF is needed. Analytical method validation is an integral part of good laboratory practice and ensures high accuracy of the results. We performed complete validation process according to the Food and Drug Administration and European Medicine Agency, covering the aspects precision, specificity, accuracy, recovery, limit of detection, limit of quantification, stability, carry-over, and matrix effects. Our liquid chromatography-tandem mass spectrometry method for the simultaneous measurement of meropenem and linezolid in different matrix meets all the acceptance criteria. The method was successfully applied to determine meropenem and linezolid concentrations in serum and CSF samples obtained from children treated with these antibiotics.

Preconception exposure to environmental antibiotics among childbearing couples in Anhui and health risk assessment: A multicenter population-based representative study

Only few studies have assessed the health effects due to preconception exposure to antibiotics among childbearing couples. This study investigated the status of preconception exposure to antibiotics among childbearing couples in Anhui, associated with health risks, and influencing factors. Overall, 1500 childbearing couples were randomly selected from the Reproductive Health of Childbearing Couples - Anhui Cohort (RHCC-AC). The urinary levels of 40 antibiotics and 2 metabolites were determined, and specific gravity (SG) adjusted concentrations of antibiotics were measured to assess health risks. Generalized linear models were used to assess the associations of urinary SG-adjusted concentration of antibiotics with demographic parameters and diet frequency. The total detection rates of all antibiotics were 98.9 % and 99.3 % in wives and husbands, respectively. The detection rates of veterinary antibiotics (VAs) and preferred as VAs (PVAs) were above 90 %. Among eight antibiotics, sulfonamides (95.1 %) and fluoroquinolones (87.6 %) had the highest detection rates in couples. Approximately four-fifths of couples were simultaneously exposed to at least three different antibiotics, and more than half of them were exposed to low concentrations of antibiotics. 8.9 % and 9.2 % of wives and husbands had hazard index value of antibiotics exposure greater than 1. Antibiotic concentrations were associated with residence, sampling season, and diet frequency. In Anhui, nearly 98 % of childbearing couples have environmental exposure to antibiotics, and VAs and PVAs are the primary antibiotics. More than 8 % of couples had health risks due to antibiotic exposure. Several potential determinants of urinary antibiotics deserve more attention in future research.

Systemic application of bone-targeting peptidoglycan hydrolases as a novel treatment approach for staphylococcal bone infection.

The rising prevalence of antimicrobial resistance in S. aureus has rendered treatment of staphylococcal infections increasingly difficult, making the discovery of alternative treatment options a high priority. Peptidoglycan hydrolases, a diverse group of bacteriolytic enzymes, show high promise as such alternatives due to their rapid and specific lysis of bacterial cells, independent of antibiotic resistance profiles. However, using these enzymes for the systemic treatment of local infections, such as osteomyelitis foci, needs improvement, as the therapeutic distributes throughout the whole host, resulting in low concentrations at the actual infection site. In addition, the occurrence of intracellularly persisting bacteria can lead to relapsing infections. Here, we describe an approach using tissue-targeting to increase the local concentration of therapeutic enzymes in the infected bone. The enzymes were modified with a short targeting moiety that mediated accumulation of the therapeutic in osteoblasts and additionally enables targeting of intracellularly surviving bacteria.

Phenomenological interpretations of the mechanism for the concentration-dependent positive effect of antibiotic lincomycin on Streptomyces coelicolor A3(2).

The antibiotic lincomycin binds to the 23S ribosomal RNA peptidyl transferase loop region to inhibit protein synthesis. However, lincomycin can also stimulate the growth and secondary metabolism of actinomycetes in a concentration-dependent manner. In Streptomyces coelicolor A3(2), lincomycin stimulates the production of the blue-pigmented antibiotic actinorhodin at concentrations below the minimum inhibitory concentration. To better understand the molecular mechanism underlying these concentration-dependent positive effects, this study investigated how the target molecule, the ribosome, undergoes dynamic changes in the presence of lincomycin and explored the ribosome-related factors involved. Lincomycin, at a concentration that stimulates actinorhodin production of S. coelicolor A3(2), could restore temporarily arrested ribosome function by utilizing ribosome-related proteins and translation factors, presumably under the control of the transcription factor WblC protein that confers intrinsic resistance to multiple translation-inhibiting antibiotics, to eventually produce stable and active ribosomes even during the late growth phase. This qualitatively and quantitatively positive ribosome alteration can be advantageous for producing actinorhodin biosynthetic enzymes. A series of gene expression and biochemical analyses revealed that lincomycin at the concentration that induces ribosomal stabilization in S. coelicolor A3(2) could influence the localization of the 20S proteasome-related proteins, resulting in reduced proteasome activity. These findings suggest that the functional analysis of 20S proteasome represents a potential pivotal challenge for understanding the molecular mechanism of ribosome stabilization induced by lincomycin. Therefore, as lincomycin can dynamically alter its target molecule, the ribosome, we discuss the future issues and prospects for an increased understanding of the concentration-dependent properties of antibiotics. IMPORTANCE Antibiotics were originally defined as chemical compounds produced by a microbe that inhibits the growth of other microbes. However, an unexplained effect of this is that a low concentration of antibiotics, such as those below the minimum inhibitory concentration, can positively affect microbial growth and metabolism. The secondary metabolic activation of streptomycetes in the presence of the translation-inhibiting antibiotic lincomycin illustrates the concentration-dependent positive effect of the antibiotic. The significance of this study is that the phenomenological interpretation of the molecular mechanism of the concentration-dependent positive effect of lincomycin in Streptomyces coelicolor A3(2) has provided novel insight into the possible role of antibiotics in making their target molecules stable and active with the assistance of various related factors that benefit their function. Further exploration of this idea would lead to an essential understanding of antibiotics, including why actinomycetes make them and their role in nature.

Low Concentrations of Antibiotics Alter Microbial Communities and Induce High Abundances of Antibiotic-Resistant Genes in Ornamental Water

Antibiotic resistance poses a significant threat to the public health domain. A favorable platform for generating and disseminating antibiotic-resistant genes (ARGs) and antibiotic-resistant bacteria (ARB) is provided by landscaped fish ponds created by urbanization. This research delved into the effects exerted by different concentrations of specific antibiotics, namely tetracycline and ciprofloxacin, on the microbial community composition present in water samples obtained from a landscape pond. Additionally, we analyzed the abundance of ARGs and the class 1 integron-integrase gene (intI1), and identified potential hosts of ARGs. The results indicated that the consistent administration of antibiotics significantly influenced the microbial community structure, resulting in variations within both bacterial communities and functionalities. Furthermore, the absolute quantities of ARGs, including tetA, tetC, qnrA, and qnrS, as well as the integrase gene intI1, exhibited augmentation in response to varying types and concentrations of antibiotics. Notably, the regular input of low concentrations of antibiotics produced higher levels of abundance of ARGs than the regular input of higher concentrations of antibiotics. The use of different types of antibiotics led to diverse host bacteria structures.

Colloid centrifugation as an alternative to antibiotics in stallion semen preparation

Antibiotics are added to semen extenders to inhibit bacterial growth and maintain sperm quality in semen doses during storage and transportation. The low concentration of antibiotics used, however, could contribute to increased antimicrobial resistance. Recent studies with boar semen suggest that centrifugation through a low density colloid could separate the spermatozoa from most of the bacteria. Such methods can only be recommended for stallion semen if they are without detrimental effects on sperm characteristics. Therefore, the purpose of this pilot study was to investigate if semen processing by single layer centrifugation through a low density colloid reduces the bacterial load of stallion semen without impairing sperm characteristics. Six healthy and fertile stallions were available at the Centre for Artificial Insemination of the University of Veterinary Medicine Vienna. One ejaculate from each stallion was collected and divided into three parts. Each part was either extended to 15 mL (100 million/mL) and processed by single layer centrifugation with 15 mL of 25% low density colloid (SLC), extended with Equiplus without antibiotics (Minitube, Tiefenbach, Germany), or kept as unprocessed control (raw semen). Aliquots from all samples were sent to the Institute of Microbiology for bacteriologicalexamination where they were serially diluted, plated onto blood agar plates, and incubated under aerobic and anaerobic conditions. The number of bacterial colony forming units (cfu/mL) was determined after 4 days of incubation. Sperm motility and viability in SLC and extended samples were evaluated by computer assisted sperm analysis (CASA; SpermVision, Minitube). The SLC and extended samples were stored at 5°C and re-evaluated after 24 h. For statistical analysis, the mean number of bacterial cfus and sperm characteristics were compared among treatments by one-way ANOVA and Tukey's test, with significance set at p < 0.05. Overall sperm yield after SLC was 76.6% (±16.4). Bacterial cfus were lower in SLC samples and extended samples compared to raw semen (4.5 × 106 cfu/mL, (14.5 × 106cfu/mL, and 8.3 × 106, respectively; p= 0.017, and p = 0.038, respectively). Sperm motility was higher in SLC samples at both time points (93.8% at 0 h, p = 0.001; 87.7% at 24h, p = 0.007) than in extended semen at 24 h (56.3%). Sperm viability was higher in the SLC at both time points (88.4% at 0 h, p = 0.0002; 86.4% at 24h, p = 0.002) than in extended semen at 24 h (73.2%). In conclusion, bacterial load, and sperm characteristics, were improved in SLC compared to extended stallion semen. An extended investigation is warranted.

Reduced selection for antibiotic resistance in community context is maintained despite pressure by additional antibiotics

Selection for antibiotic resistance at very low antibiotic concentrations has been demonstrated for individual antibiotics in single species experiments. Furthermore, selection in these focal strains is reduced when taking place in complex microbial community context. However, in the environment, bacteria are rarely exposed to single, but rather complex mixtures of selective agents. Here, we explored how the presence of a second selective agent affects selection dynamics between isogenic pairs of focal E. coli strains, differing exclusively in a single resistance determinant, in the absence and presence of a model wastewater community across a gradient of antibiotics. An additional antibiotic that exclusively affects the model wastewater community, but to which the focal strains are resistant to, was chosen as the second selective agent. This allowed exploring how inhibition alters the community’s ability to reduce selection. In the presence of the community, the selection coefficient at specific antibiotic concentrations was consistently decreased compared to the absence of the community. While pressure through the second antibiotic significantly decreased the activity and diversity of the community, its ability to reduce selection was consistently maintained at levels comparable to those recorded in absence of the second antibiotic. This indicates that the observed effects of community context on selection dynamics are rather based on competitive or protective effects between the focal strains and a small proportion of bacteria within the community, than on general competition for nutrients. These findings have implications for our understanding of the evolution and selection for multi-drug resistant strains.

Removal of low-concentration tetracycline from water by a two-step process of adsorption enrichment and photocatalytic regeneration

Developing a high-performance method that can effectively control pollution caused by low concentrations of antibiotics is urgently needed. Herein, a novel three-dimensional PPy/Zn3In2S6 nanoflower composites were prepared for the comprehensive treatment of low-concentration tetracycline (Tc) hydrochloride in wastewater based on the adsorption/photocatalysis of Zn3In2S6 and the conductivity of PPy. In this preparation method, adsorption enrichment and photocatalytic regeneration were conducted in two steps, eliminating the dilution and dispersion effects of aqueous solvents on photocatalytic species and antibiotics. Results showed that Zn3In2S6 could effectively adsorb 87.85% of Tc at pH of 4.5 and photocatalytically degrade Tc at pH of 10.5. Although the adsorption capacity of Zn3In2S6 was slightly reduced after being combined with PPy, its photocatalytic efficiency was substantially enhanced. Specifically, 0.5%PPy/Zn3In2S6 could degrade 99.92% of the surface-enriched Tc in 1 h and induce the regeneration of the adsorption sites. Furthermore, the adsorption capacity remained above 85% even after recycling PPy/Zn3In2S6 ten times. The photocatalytic degradation mechanism analysis revealed that the enrichment of Tc on 0.5%PPy/Zn3In2S6 negatively impacts the photocatalytic efficiency, while •O2− and •OH radicals were the main oxidative species that played an important role in the photoregeneration process.

Epigenetic-Based Regulation of Transcriptome in Escherichia coli Adaptive Antibiotic Resistance.

Adaptive antibiotic resistance is a transient metabolic adaptation of bacteria limiting their sensitivity to low, progressively increased, concentrations of antibiotics. Unlike innate and acquired resistance, adaptive resistance is dependent on the presence of antibiotics, and it disappears when the triggering factor is removed. Low concentrations of antibiotics are largely diffused in natural environments, in the food industry or in certain body compartments of humans when used therapeutically, or in animals when used for growth promotion. However, molecular mechanisms underlying this phenomenon are still poorly characterized. Here, we present experiments suggesting that epigenetic modifications, triggered by low concentrations of ampicillin, gentamicin, and ciprofloxacin, may modulate the sensitivity of bacteria to antibiotics. The epigenetic modifications we observed were paralleled by modifications of the expression pattern of many genes, including some of those that have been found mutated in strains with permanent antibiotic resistance. As the use of low concentrations of antibiotics is spreading in different contexts, our findings may suggest new targets and strategies to avoid adaptive antibiotic resistance. This might be very important as, in the long run, this transient adaptation may increase the chance, allowing the survival and the flourishing of bacteria populations, of the onset of mutations leading to stable resistance. IMPORTANCE In this study, we characterized the modifications of epigenetic marks and of the whole transcriptome in the adaptive response of Escherichia coli cells to low concentrations of ampicillin, gentamicin, and ciprofloxacin. As the transient adaptation does increase the chance of permanent resistance, possibly allowing the survival and flourishing of bacteria populations where casual mutations providing resistance may give an immediate advantage, the importance of this study is not only in the identification of possible molecular mechanisms underlying adaptive resistance to antibiotics, but also in suggesting new strategies to avoid adaptation.

Gut microbiota interspecies interactions shape the response of Clostridioides difficile to clinically relevant antibiotics.

In the human gut, the growth of the pathogen Clostridioides difficile is impacted by a complex web of interspecies interactions with members of human gut microbiota. We investigate the contribution of interspecies interactions on the antibiotic response of C. difficile to clinically relevant antibiotics using bottom-up assembly of human gut communities. We identify 2 classes of microbial interactions that alter C. difficile's antibiotic susceptibility: interactions resulting in increased ability of C. difficile to grow at high antibiotic concentrations (rare) and interactions resulting in C. difficile growth enhancement at low antibiotic concentrations (common). Based on genome-wide transcriptional profiling data, we demonstrate that metal sequestration due to hydrogen sulfide production by the prevalent gut species Desulfovibrio piger increases the minimum inhibitory concentration (MIC) of metronidazole for C. difficile. Competition with species that display higher sensitivity to the antibiotic than C. difficile leads to enhanced growth of C. difficile at low antibiotic concentrations due to competitive release. A dynamic computational model identifies the ecological principles driving this effect. Our results provide a deeper understanding of ecological and molecular principles shaping C. difficile's response to antibiotics, which could inform therapeutic interventions.

Progressive Sub-MIC Exposure of Klebsiella pneumoniae 43816 to Cephalothin Induces the Evolution of Beta-Lactam Resistance without Acquisition of Beta-Lactamase Genes.

Bacterial exposure to antibiotic concentrations below the minimum inhibitory concentration (MIC) may result in a selection window allowing for the rapid evolution of resistance. These sub-MIC concentrations are commonly found in soils and water supplies in the greater environment. This study aimed to evaluate the adaptive genetic changes in Klebsiella pneumoniae 43816 after prolonged but increasing sub-MIC levels of the common antibiotic cephalothin over a fourteen-day period. Over the course of the experiment, antibiotic concentrations increased from 0.5 μg/mL to 7.5 μg/mL. At the end of this extended exposure, the final adapted bacterial culture exhibited clinical resistance to both cephalothin and tetracycline, altered cellular and colony morphology, and a highly mucoid phenotype. Cephalothin resistance exceeded 125 μg/mL without the acquisition of beta-lactamase genes. Whole genome sequencing identified a series of genetic changes that could be mapped over the fourteen-day exposure period to the onset of antibiotic resistance. Specifically, mutations in the rpoB subunit of RNA Polymerase, the tetR/acrR regulator, and the wcaJ sugar transferase each fix at specific timepoints in the exposure regimen where the MIC susceptibility dramatically increased. These mutations indicate that alterations in the secretion of colanic acid and attachment of colonic acid to LPS may contribute to the resistant phenotype. These data demonstrate that very low sub-MIC concentrations of antibiotics can have dramatic impacts on the bacterial evolution of resistance. Additionally, this study demonstrates that beta-lactam resistance can be achieved through sequential accumulation of specific mutations without the acquisition of a beta-lactamase gene.

Gut redox potential affects host susceptibility to pathogen infection

Redox potential is a key environmental indicator in the gut and also significantly affects host health. To study the influence of gut redox potential on the infection of hosts by pathogen, we employed zebrafish and common carp as animal models to investigate the relationship between gut redox potential and host susceptibility. Our results proved that gut redox potential was significantly elevated after host infection with pathogenic bacteria. Moreover, the level of reactive oxygen species (ROS) was significantly and positively correlated with gut redox potential. Reduction of the gut redox potential with antioxidants significantly improved host resistance to pathogen infections. In addition, when the host was infected with pathogen, the reduction of gut redox potential could improve survival. Interestingly, the combination of antioxidants and low concentrations of antibiotics could achieve a similar therapeutic effect to that of a single high concentration of antibiotics by reducing the gut redox potential. Overall, this study proved that altered redox potential could aid in the host resistance to infection, and also provides new perspectives for the treatment of pathogen infections.