Ciprofloxacin Treatment Research Articles

Effect of H2S and cysteine homeostasis disturbance on ciprofloxacin sensitivity of Escherichia coli in cystine-free and cystine-fed minimal medium.

Endogenous H2S has been proposed to be a universal defense mechanism against different antibiotics. Here, we studied the role of H2S transiently generated during ciprofloxacin (CF) treatment in M9 minimal medium with sulfate or produced by E. coli when fed with cystine. The cysM and mstA mutants did not produce H2S, while gshA generated more H2S in response to ciprofloxacin in cystine-free media. All mutants showed a reduced ability to maintain cysteine homeostasis under these conditions. We found no relationship between H2S generation, cysteine concentration and sensitivity to ciprofloxacin. Excess cysteine, which occurred during E. coli growth in cystine-fed media, triggered continuous H2S production, accelerated glutathione synthesis and cysteine export. This was accompanied by a twofold increase in ciprofloxacin tolerance in all strains except gshA, whose sensitivity increased 5-8-fold at high CF doses, indicating the importance of GSH in restoring the intracellular redox situation during growth in cystine-fed media.

Enhanced Photocatalytic Degradation of Ciprofloxacin Antibiotics using Fe3O4-SiO2-EN@Zn-Al Layered Double Hydroxide Nanocomposites under the COVID-19 pandemic

A novel layered double hydroxide nanocomposite, Fe3O4-SiO2-EN@Zn-Al-LDH, was synthesized and employed as a photocatalyst for the degradation of ciprofloxacin (CIP) in aqueous solutions. Characterization of the photocatalyst was performed using scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), and Brunauer-Emmett-Teller (BET) techniques. The results indicated successful synthesis of particle with specific surface area of 28.67 m²/g, pore size of 1.64 nm, and pore volume of 6.58 cm³/g. Optimal degradation of CIP was observed under the following conditions: pH 5, photocatalyst dosage of 0.6 g/L, initial CIP concentration of 25 mg/L, and an irradiation duration of 60 minutes. Comparative experiments demonstrated that incorporating Zn-Al LDH with core-shell nanoparticles (Fe3O4-SiO2-EN) enhanced removal efficiency by 2.5 to 6 times compared to individual materials. The composite exhibited efficient activation under UV, visible light, and solar radiation, resulting in 100% degradation of CIP under UV, 100% under visible light, and 81.4% under solar radiation. Biodegradability, indicated by the BOD5/COD ratio, increased from 0.28 to 0.73 after 120 minutes of photocatalytic oxidation under visible light, with 80.83% COD removal and 74.17% TOC removal. Reactive species generation, such as •OH, •O2-, and h+, was confirmed by introducing scavengers (TBA, BQ, and TEOS) into the reaction medium. The photocatalytic activity of the nanocomposite was slightly decreased over 5 consecutive CIP treatment cycles. Toxicity assessment of treated wastewater using E. coli and Daphnia magna bioassays revealed a significant decrease in E. coli growth inhibition rate with prolonged treatment time. The EC50 percentage improved from 1.27% to 97.4% after 4 hours of CIP treatment under visible light. In conclusion, the development of the Fe3O4-SiO2-EN@Zn-Al-LDH presents a noteworthy advancement in photocatalysis for the degradation of CIP in aqueous solutions.

The adverse effect of ciprofloxacin treatment can be related to the increased thermal stability of monomeric actin

AbstractActin is a major component of all sarcomere and cytoskeletal systems and thus plays a crucial role in muscle and cellular movement. The molecular dynamics of actomyosin complexes are obtaining the central machinery of force generation during contraction. Nalidixic acid, discovered in 1962—the primary compound of the quinolone, fluoroquinolone-type antibiotics—in the forms of its improved derivatives are still widely used today. One of the most commonly used drugs in this class is ciprofloxacin (CF). It was observed that after the use of these drugs—during longer or shorter administration or even after their use—several side effects such as muscle pain (myalgia), muscle spasms, and muscle atrophy also occur, and muscle damage and rupture may be associated with muscle cell death (rhabdomyolysis). In medical cases, muscle weakness after CF treatment can be related to the CF-actin interaction. Here, we studied the effect of CF on skeletal muscle actin using differential scanning calorimetry (DSC). We obtained evident data that CF binding increases the structural stability of G actin and slightly weakens the F actin filaments. The stability change of actin in myofilaments can lead to the adverse effect of CF.

Effect of environmental factors on adsorption of ciprofloxacin from wastewater by microwave alkali modified fly ash

Antibiotics, as emerging persistent pollutants, pose significant threats to human health. The effective and low-cost removal of ciprofloxacin (CIP) from wastewater has become an important research focus. In this study, fly ash (FA) was used as the raw material, and modified fly ash (MFA) was prepared by varying microwave power, alkali concentration, and immersion time to investigate its adsorption characteristics for CIP. Results showed that the optimal preparation conditions for MFA with the most effective adsorption of CIP, using the Box-Behnken response surface methodology, were a microwave power of 480 W, an alkali concentration of 1.5 mol/L, and a modification time of 3 h. Scanning electron microscopy, Fourier transform infrared spectroscopy, and X-ray diffraction analyses revealed that after modification, the glassy structure of FA is destroyed, the specific surface area is increased, and obvious hydroxyl O–H absorption peaks appear. Both FA and MFA exhibited adsorption processes for CIP that conformed to pseudo-second-order kinetics and the Langmuir equation. Maximum adsorption of CIP (9.61 and 12.67 mg/g) was achieved at pH = 6. With increasing temperature, the adsorption capacity of both FA and MFA for CIP decreased, indicating an exothermic process. The adsorption capacity of CIP decreased with increasing ion concentration, with the impact order of ions being Al3+ > Ca2+ > Na+. The results show that pore filling, electrostatic interaction, ion exchange and complexation are the main ways of CIP adsorption by FA. Microwave alkali modified fly ash is an economical and efficient adsorbent for CIP removal in water, realizing the purpose of “treating waste with waste”. This study provides a scientific basis for controlling CIP treatment in wastewater.

Exploring the efficiency of nitrogenated carbon quantum dots/TiO2 S-scheme heterojunction in the photodegredation of ciprofloxacin in aqueous environments.

In this study, we developed a heterojunction photocatalyst, namely nitrogen-doped carbon quantum dots/titanium dioxide (N-CQDs/TiO2), for the effective and sustainable treatment of ciprofloxacin (CIP) antibiotic in aqueous solution. First, N-CQDs were prepared from a chitosan biopolymer with a green, facile, and effective hydrothermal carbonization technique and then anchored on the TiO2 surface via a hydrothermal process. The morphological, structural, and optical properties of the as-prepared materials were characterized by using advanced analytical techniques. The impacts of the mass percentage of N-CQDs, catalyst and CIP concentration, and pH on photocatalytic CIP degradation were investigated in depth. Comparative analyses were performed to evaluate different processes including adsorption, photolysis, and photocatalysis for the removal of CIP with TiO2 and N-CQDs/TiO2. The results revealed that N-CQDs/TiO2 exhibited the highest CIP removal efficiency of up to 83.91% within 120 min using UVA irradiation under optimized conditions (10 mg/L CIP, 0.4 g/L catalyst, and pH 5). Moreover, the carbon source used in the fabrication of N-CQDs was also considered, and lower removal efficiency was obtained when glucose was used as a carbon source instead of chitosan. This excellent improvement in CIP degradation was attributed to the ideal separation and migration of photogenerated carriers, strong redox capability, and high generation of reactive oxygen species provided by the successful construction of the N-CQDs/TiO2 S-scheme heterojunction. Scavenger experiments indicated that h+ and •OH reactive oxygen species were the predominant factors for CIP elimination in water. Overall, this study presents a green synthesis approach for N-CQDs/TiO2 heterojunction photocatalysts using natural materials, demonstrating potential as a cost-effective and efficient method for pharmaceutical degradation in water treatment applications.

Effect of Early Ciprofloxacin Administration on Growth Performance, Meat Quality, Food Safety, and Metabolomic Profiles in Xueshan Chickens.

To investigate the effects of early administration of ciprofloxacin (CIP) on Xueshan chickens, in this study Xueshan chickens were measured for growth performance, tested for drug residues, evaluated for meat quality, and muscle metabolism changes were explored using a non-target metabolomics approach. Experimental findings revealed that early CIP use did not significantly impact the overall growth rate of Xueshan chickens (p > 0.05). However, notable alterations in meat quality were observed: the CIP-treated group exhibited a significant decrease in muscle pH (pH1 and pH24) and a marked increase in drip loss and moisture content (p > 0.05). No CIP residues were detected in muscle tissue. Untargeted metabolomics analyses unveiled significant alterations in the metabolic profile of market-age chickens following CIP treatment. Both functional enrichment and metabolic network analyses indicated significant effects on the ko01120 (microbial metabolism in diverse environments) and ko00350 (tyrosine metabolism) pathways, implying that CIP treatment may influence chicken meat quality by modulating microbial communities and amino acid metabolism. This study provides a crucial foundation for understanding the impact of antibiotics on meat quality and metabolism in poultry production, offering scientific insights for optimizing antibiotic-use strategies and safeguarding poultry product quality.

The Food Additive Benzaldehyde Confers a Broad Antibiotic Tolerance by Modulating Bacterial Metabolism and Inhibiting the Formation of Bacterial Flagella.

The rise of antibiotic tolerance in bacteria harboring genetic elements conferring resistance to antibiotics poses an increasing threat to public health. However, the primary factors responsible for the emergence of antibiotic tolerance and the fundamental molecular mechanisms involved remain poorly comprehended. Here, we demonstrate that the commonly utilized food additive Benzaldehyde (BZH) possesses the capacity to induce a significant level of fluoroquinolone tolerance in vitro among resistant Escherichia coli. Our findings from animal models reveal that the pre-administration of BZH results in an ineffective eradication of bacteria through ciprofloxacin treatment, leading to similar survival rates and bacterial loads as observed in the control group. These results strongly indicate that BZH elicits in vivo tolerance. Mechanistic investigations reveal several key factors: BZH inhibits the formation of bacterial flagella and releases proton motive force (PMF), which aids in expelling antibiotics from within cells to reducing their accumulation inside. In addition, BZH suppresses bacterial respiration and inhibits the production of reactive oxygen species (ROS). Moreover, exogenous pyruvate successfully reverses BZH-induced tolerance and restores the effectiveness of antibiotics, highlighting how crucial the pyruvate cycle is in combating antibiotic tolerance. The present findings elucidate the underlying mechanisms of BZH-induced tolerance and highlight potential hazards associated with the utilization of BZH.

Salmonella Typhimurium alters galactitol metabolism under ciprofloxacin treatment to balance resistance and virulence.

Treatment of antibiotic resistance can significantly benefit from a deeper understanding of the interactions between drugs and genetics. The physiological responses and genetic mechanisms in antibiotic-exposed bacteria are not well understood. Traditional resistance studies, often retrospective, fail to capture the entire resistance development process and typically exhibit unpredictable dynamics. To explore how clinical isolates of S. Typhimurium respond to ciprofloxacin, we analyzed their adaptive responses. We found that S. Typhimurium RamA-mediated regulation disrupts microbial metabolism under ciprofloxacin exposure, affecting genes in the galactitol metabolic pathways. This disruption facilitates adaptive responses to drug therapy and enhances the efficiency of intracellular survival. A more comprehensive and integrated understanding of these physiological and genetic changes is crucial for improving treatment outcomes.

Small RNA GadY in Escherichia coli enhances conjugation system of IncP-1 by targeting SdiA.

Plasmid-mediated conjugation is a common mechanism for most bacteria to transfer antibiotic resistance genes (ARGs). The conjugative transfer of ARGs is emerging as a major threat to human beings. Although several transfer-related factors are known to regulate this process, small RNAs (sRNAs)-based regulatory roles remain to be clarified. Here, the Hfq-binding sRNA GadY in donor strain Escherichia coli (E. coli) SM10λπ was identified as a new regulator for bacterial conjugation. Two conjugation models established in our previous studies were used, which SM10λπ carrying a chromosomally integrated IncP-1α plasmid RP4 and a mobilizable plasmid pUCP24T served as donor cells, and P. aeruginosa PAO1 or E. coli EC600 as the recipients. GadY was found to promote SM10λπ-PAO1 conjugation by base-pairing with its target mRNA SdiA, an orphan LuxR-type receptor that responds to exogenous N-acylated homoserine lactones (AHLs). However, SM10λπ-EC600 conjugation was not affected due to EC600 lacking AHLs synthase. It indicates that the effects of GadY on conjugation depended on AHLs-SdiA signalling. Further study found GadY bound SdiA to negatively regulate the global RP4 repressors KorA and KorB. When under ciprofloxacin or levofloxacin treatment, GadY expression in donor strain was enhanced, and it positively regulated quinolone-induced SM10λπ-PAO1 conjugation. Thus, our study provides a novel role for sRNA GadY in regulating plasmid-mediated conjugation, which helps us better understand bacterial conjugation to counter antibiotic resistance.

A biochemical assessment of apoptosis-inducing impact of Salinomycin in combination with ciprofloxacin on human leukemia KG1-a stem-like cells in the presence and absence of insulin.

Acute Myeloid Leukemia (AML) is a fast-developing invading cancer that impacts the blood and bone marrow, marked by the rapid proliferation of abnormal white blood cells. Chemotherapeutic agents, a primary treatment for AML, encounter clinical limitations such as poor solubility and low bioavailability. Previous studies have highlighted antibiotics as effective in inducing cancer cell death and potentially preventing metastasis. Besides, insulin is known to activate the PI3K/Akt pathway, often disrupted in cancers, leading to enhanced cell survival and resistance to apoptosis. In light of the above-mentioned points, we examined the anti-cancer impact of antibiotics Ciprofloxacin (CP) and Salinomycin (SAL) and their combination on KG1-a cells in the presence and absence of insulin. This was accomplished by exposing KG1-a cells to different doses of CP and SAL alone, in combination, and with or without insulin for 24-72h. Cell viability was evaluated using the MTT assay. Besides, apoptotic effects were examined using Hoechst staining and Annexin-V/PI flow cytometry. The expression levels of Bax, p53, BIRC5, Akt, PTEN, and FOXO1 were analyzed through Real-Time PCR. CP and SAL demonstrated cytotoxic and notable pro-apoptotic impact on KG1-a cells by upregulating Bax and p53 and downregulating BIRC5, leading to G0/G1 cell cycle arrest and prevention of the PI3K-Akt signaling pathway. Our findings demonstrated that combination of CP and SAL promote apoptosis in the KG1-a cell line by down-regulating BIRC5 and Akt, as well as up-regulating Bax, p53, PTEN, and FOXO1. Additionally, the findings strongly indicated that insulin effectively mitigates apoptosis by enhancing Akt expression and reducing FOXO1 and PTEN gene expression in the cells treated with CP and SAL. Our findings showed that the combined treatment of CP and SAL exhibit a strong anti-cancer effect on leukemia KG1-a cells. Moreover, it was discovered that the PI3K-Akt signaling can be a promising target in leukemia treatment particularly in hyperinsulinemia condition.

A high-throughput assay identifies molecules with antimicrobial activity against persister cells.

Introduction. Persister cells are transiently non-growing antibiotic-tolerant bacteria that cause infection relapse, and there is no effective antibiotic therapy to tackle these infections.Gap statement. High-throughput assays in drug discovery are biased towards detecting drugs that inhibit bacterial growth rather than killing non-growing bacteria. A new and simple assay to discover such drugs is needed.Aim. This study aims to develop a simple and high-throughput assay to identify compounds with antimicrobial activity against persister cells and use it to identify molecular motifs with such activity.Methodology. We quantified Staphylococcus aureus persister cells by enumeration of colony forming units after 24 h ciprofloxacin treatment. We first quantified how the cell concentration, antibiotic concentration, growth phase and presence/absence of nutrients during antibiotic exposure affected the fraction of persister cells in a population. After optimizing these parameters, we screened the antimicrobial activity of compound fragments to identify molecular structures that have activity against persister cells.Results. Exponential- and stationary-phase cultures transferred to nutrient-rich media displayed a bi-phasic time-kill curve and contained 0.001-0.07% persister cells. A short rifampicin treatment resulted in 100% persister cells for 7 h, after which cells resumed activity and became susceptible. Stationary-phase cultures displayed a low but constant death rate but ultimately resulted in similarly low survival rates as the exponential-phase cultures after 24 h ciprofloxacin treatment. The persister phenotype was only maintained in most of the population for 24 h if cells were transferred to a carbon-free minimal medium before exposure to ciprofloxacin. Keeping cells starved enabled the generation of high concentrations of S. aureus cells that tolerate 50× MIC ciprofloxacin, and we used this protocol for rapid screening for biocidal antibiotics. We identified seven compounds from four structural clusters with activity against antibiotic-tolerant S. aureus. Two compounds were moderately cytotoxic, and the rest were highly cytotoxic.Conclusion. Transferring a stationary-phase culture to a carbon-free minimal medium for antimicrobial testing is a simple strategy for high-throughput screening for new antibiotics that kill persister cells. We identified molecule fragments with such activity, but further screening is needed to identify motifs with lower general cytotoxicity.

Gut microbiota and serum metabolomic alterations in modulating the impact of fecal microbiota transplantation on ciprofloxacin-induced seizure susceptibility.

The gut microbiota and the microbiota-gut-brain axis have gained considerable attention in recent years, emerging as key players in the mechanisms that mediate the occurrence and progression of many central nervous system-related diseases, including epilepsy. In clinical practice, one of the side effects of quinolone antibiotics is a lower seizure threshold or aggravation. However, the underlying mechanism remains unclear. We aimed to unravel the intrinsic mechanisms through 16S rRNA sequencing and serum untargeted metabolomic analysis to shed light on the effects of gut microbiota in ciprofloxacin-induced seizure susceptibility and lithium pilocarpine-induced epilepsy rat models. We observed that ciprofloxacin treatment increased seizure susceptibility and caused gut dysbiosis. We also found similar changes in the gut microbiota of rats with lithium pilocarpine-induced epilepsy. Notably, the levels of Akkermansia and Bacteroides significantly increased in both the ciprofloxacin-induced seizure susceptibility and lithium pilocarpine-induced epilepsy rat models. However, Marvinbryantia, Oscillibacter, and Ruminococcaceae_NK4A214_group showed a coincidental reduction. Additionally, the serum untargeted metabolomic analysis revealed decreased levels of indole-3-propionic acid, a product of tryptophan-indole metabolism, after ciprofloxacin treatment, similar to those in the plasma of lithium pilocarpine-induced epilepsy in rats. Importantly, alterations in the gut microbiota, seizure susceptibility, and indole-3-propionic acid levels can be restored by fecal microbiota transplantation. In summary, our findings provide evidence that ciprofloxacin-induced seizure susceptibility is partially mediated by the gut microbiota and tryptophan-indole metabolism. These associations may play a role in epileptogenesis, and impacting the development progression and treatment outcomes of epilepsy.

Effects of ciprofloxacin and levofloxacin on initial colonization of intestinal microbiota in Bufo gargarizans at embryonic stages

Ciprofloxacin (CIP) and levofloxacin (LEV) are broad-spectrum antibiotics with potent antibacterial activity. Although many studies have shown that antibiotics can lead to gut microbiota disruption, the effects of CIP and LEV on gut microbial colonization at the embryonic stage remain poorly characterized. Here, we evaluated the response of Bufo gargarizans embryos in terms of gut microbiota colonization, growth and developmental stages to CIP and LEV exposure. Embryos treated with 100 μg/L CIP and LEV exhibited significantly reduced diversity and richness of the gut microbiota, as well as altered community structure. Both CIP and LEV treatments resulted in an increase in the pathogenic bacteria Bosea and Aeromonas, and they appeared to be more resistant to CIP than LEV. Additionally, CIP exposure caused reduced total length and delayed the development in B. gargarizans embryos, while LEV increased the total length and promoted embryonic development. The present study revealed the adverse effects of CIP and LEV exposure on host gut microbiota, growth and development during the embryonic stage, and contributed new perspectives to the evaluation of early aquatic ecological risk under CIP and LEV exposure.

A phase ib clinical trial of oral ciprofloxacin and etoposide in subjects with resistant acute myeloid leukemia

A phase 1b study was conducted to evaluate the safety and feasibility of ciprofloxacin and etoposide combination treatment in subjects with relapsed and refractory acute myeloid leukemia. Eleven subjects were enrolled in the study. Utilizing the standard ‘3 + 3’ design, escalating ciprofloxacin doses (750 mg, 1000 mg) twice daily on D1-D10 in combination with a fixed dose (200 mg) of etoposide on D2-D8 were administered. Maximum tolerated dose was determined to be 1000 mg of ciprofloxacin in combination with 200 mg of etoposide. Serious adverse events occurred in 54.5% (n = 6) subjects and 91% (n = 10) subjects reported ≥ grade 3 toxicities. Nine subjects completed treatment, one had a dose-limiting toxicity, and one withdrew. One subject achieved complete remission with a duration of 111 days and one subject achieved morphologic leukemia-free state after cycle 1. While the combination demonstrated safety and an acceptable toxicity profile, only modest hematologic and clinical benefits were observed. This trial was registered at www.clinicaltrials.gov as #NCT02773732.

Novel photocatalyst for fast treatment of ciprofloxacin and crystal violet pollutants: In3+-doped CuO/CuMn2O4 nanocomposite

Novel photocatalyst for fast treatment of ciprofloxacin and crystal violet pollutants: In3+-doped CuO/CuMn2O4 nanocomposite

Perovskite-type strontium ferrite-based catalyst: Characterization and antibiotic degradation approach

Ciprofloxacin (CIP) is a commonly found pharmaceutical in industrial and residential wastewater. This study aimed to synthesize and characterize a catalyst based on strontium ferrite of the perovskite-type (SrFeO3) to reduce CIP. The sol-gel method was employed to synthesize SrFeO3, resulting in a material with dense characteristics and uniform distribution of metallic species on the surface. Various approaches to pollutant removal were examined, including catalysis in the dark (PerCIP1), photocatalysis (PerCIP2), and a combination of darkness and light (PerCIP3). The optimized conditions for CIP treatment were a pH of 6, a pollutant concentration of 10 ppm, and a reaction time of 6 hours. Under these conditions, PerCIP1, PerCIP2, and PerCIP3 achieved removal efficiencies of 53%, 80%, and 75%, respectively. Analysis of the CIP degradation mechanism suggested a sequence involving an adsorption step, followed by the generation of reactive species and, ultimately, CIP oxidation. Furthermore, the catalyst exhibited excellent stability, maintaining its catalytic activity even after four reuse cycles without requiring a regeneration step. Phytotoxicity experiments indicated a reduced toxicity in the treated solution compared to the initial contaminant solution. In conclusion, the synthesized catalyst demonstrated promising characteristics for the aqueous treatment of CIP.

Doxycycline, levofloxacin, and moxifloxacin are superior to ciprofloxacin in treating anthrax meningitis in rabbits and NHP.

Efficient treatment of anthrax-related meningitis in patients poses a significant therapeutic challenge. Previously, we demonstrated in our anthrax meningitis rabbit model that ciprofloxacin treatment is ineffective with most of the treated animals succumbing to the infection. Herein we tested the efficacy of doxycycline in our rabbit model and found it highly effective. Since all of our findings are based on a rabbit model, we test the efficacy of ciprofloxacin or doxycycline in a specific central nervous system (CNS) model developed in non-human primates (NHPs). Similar to rabbits, ciprofloxacin treatment was ineffective, while doxycycline protected the infected rhesus macaques (n = 2) from the lethal CNS Bacillus anthracis infection. To test whether the low efficacy of Ciprofloxacin is an example of low efficacy of all fluoroquinolones or only this substance, we treated rabbits that were inoculated intracisterna magna (ICM) with levofloxacin or moxifloxacin. We found that in contrast to ciprofloxacin, levofloxacin and moxifloxacin were highly efficacious in treating lethal anthrax-related meningitis in rabbits and NHP (levofloxacin). We demonstrated (in naïve rabbits) that this difference probably results from variances in blood-brain-barrier penetration of the different fluoroquinolones. The combined treatment of doxycycline and any one of the tested fluoroquinolones was highly effective in the rabbit CNS infection model. The combined treatment of doxycycline and levofloxacin was effective in an inhalation rabbit model, as good as the doxycycline mono-therapy. These findings imply that while ciprofloxacin is highly effective as a post-exposure prophylactic drug, using this drug to treat symptomatic patients should be reconsidered.

Metagenomic and transcriptomic analysis revealing the impact of oxytetracycline and ciprofloxacin on gut microbiota and gene expression in the Chinese giant salamander (Andrias davidianus)

Excessive antibiotic use has led to the spread of antibiotic resistance genes (ARGs), impacting gut microbiota and host health. However, the effects of antibiotics on amphibian populations remain unclear. We investigated the impact of oxytetracycline (OTC) and ciprofloxacin (CIP) on Chinese giant salamanders (Andrias davidianus), focusing on gut microbiota, ARGs, and gene expression by performing metagenome and transcriptome sequencing. A. davidianus were given OTC (20 or 40 mg/kg) or CIP (50 or 100 mg/kg) orally for 7 days. The results revealed that oral administration of OTC and CIP led to distinct changes in microbial composition and functional potential, with CIP treatment having a greater impact than OTC. Antibiotic treatment also influenced the abundance of ARGs, with an increase in fluoroquinolone and multi-drug resistance genes observed post-treatment. The construction of metagenome-assembled genomes (MAGs) accurately validated that CIP intervention enriched fish-associated potential pathogens Aeromonas hydrophila carrying an increased number of ARGs. Additionally, mobile genetic elements (MGEs), such as phages and plasmids, were implicated in the dissemination of ARGs. Transcriptomic analysis of the gut revealed significant alterations in gene expression, particularly in immune-related pathways, with differential effects observed between OTC and CIP treatments. Integration of metagenomic and transcriptomic data highlighted potential correlations between gut gene expression and microbial composition, suggesting complex interactions between the host gut and its gut microbiota in response to antibiotic exposure. These findings underscore the importance of understanding the impact of antibiotic intervention on the gut microbiome and host health in amphibians, particularly in the context of antibiotic resistance and immune function.

Veterinary antibiotics differ in phytotoxicity on oilseed rape grown over a wide range of concentrations

Residues of veterinary antibiotics are a worldwide problem of increasing concern due to their persistence and diverse negative effects on organisms, including crops, and limited understanding of their phytotoxicity. Therefore, this study aimed to compare the phytotoxic effects of veterinary antibiotics tetracycline (TC) and ciprofloxacin (CIP) applied in a wide range of concentrations on model plant oilseed rape (Brassica napus). Overall phytotoxicity of 1–500 mg kg−1 of TC and CIP was investigated based on morphological, biochemical, and physiological plant response. Photosystem II (PSII) performance was suppressed by TC even under environmentally relevant concentration (1 mg kg−1), with an increasing effect proportionally to TC concentration in soil. In contrast, CIP was found to be more phytotoxic than TC when applied at high concentrations, inducing a powerful oxidative burst, impairment of photosynthetic performance, collapse of antioxidative protection and sugar metabolism, and in turn, complete growth retardation at 250 and 500 mg kg−1 CIP treatments. Results of our study suggest that TC and CIP pollution do not pose a significant risk to oilseed rapes in many little anthropogenically affected agro-environments where TC or CIP concentrations do not exceed 1 mg kg−1; however, intensive application of manure with high CIP concentrations (more than 50 mg kg−1) might be detrimental to plants and, in turn, lead to diminished agricultural production and a potential risk to human health.

Impact of suppression of the SOS response on protein expression in clinical isolates of Escherichia coli under antimicrobial pressure of ciprofloxacin.

Suppression of the SOS response in combination with drugs damaging DNA has been proposed as a potential target to tackle antimicrobial resistance. The SOS response is the pathway used to repair bacterial DNA damage induced by antimicrobials such as quinolones. The extent of lexA-regulated protein expression and other associated systems under pressure of agents that damage bacterial DNA in clinical isolates remains unclear. The aim of this study was to assess the impact of this strategy consisting on suppression of the SOS response in combination with quinolones on the proteome profile of Escherichia coli clinical strains. Five clinical isolates of E. coli carrying different chromosomally- and/or plasmid-mediated quinolone resistance mechanisms with different phenotypes were selected, with E. coli ATCC 25922 as control strain. In addition, from each clinical isolate and control, a second strain was created, in which the SOS response was suppressed by deletion of the recA gene. Bacterial inocula from all 12 strains were then exposed to 1xMIC ciprofloxacin treatment (relative to the wild-type phenotype for each isogenic pair) for 1 h. Cell pellets were collected, and proteins were digested into peptides using trypsin. Protein identification and label-free quantification were done by liquid chromatography-mass spectrometry (LC-MS) in order to identify proteins that were differentially expressed upon deletion of recA in each strain. Data analysis and statistical analysis were performed using the MaxQuant and Perseus software. The proteins with the lowest expression levels were: RecA (as control), AphA, CysP, DinG, DinI, GarL, PriS, PsuG, PsuK, RpsQ, UgpB and YebG; those with the highest expression levels were: Hpf, IbpB, TufB and RpmH. Most of these expression alterations were strain-dependent and involved DNA repair processes and nucleotide, protein and carbohydrate metabolism, and transport. In isolates with suppressed SOS response, the number of underexpressed proteins was higher than overexpressed proteins. High genomic and proteomic variability was observed among clinical isolates and was not associated with a specific resistant phenotype. This study provides an interesting approach to identify new potential targets to combat antimicrobial resistance.