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Conventional wastewater treatment plants (WWTPs) are not designed for the abatement of antibiotics, and their effluents are one of the main entry ways of these emerging contaminants to the aquatic environment, causing major concern due to their toxicity, persistence, and bioaccumulation. When wastewater containing antibiotics enters the bioreactor, they can impact microbial communities of the activated sludge, affecting biodegradation processes of organic matter and nutrients. There is scarce information about the effect of activated carbon on the activated sludge within the bioreactor in presence of antibiotics. In light of this, the effect of representative antibiotics, ciprofloxacin (CIP), nalidixic acid (NAL), and erythromycin (ERY), on the performance of a conventional activated sludge of a WWTP was analyzed by respirometry with and without activated carbon. NAL and ERY negatively affected the net heterotrophic biomass growth rate (r′x,H), with reduction percentages of 26%–90% and 31%–81%, respectively. The addition of activated carbon mitigated this effect, especially for ERY, with increments of even 8% in the r′x,H for the hybrid process when working with 5 ppm of ERY and 80 ppm of activated carbon compared with the value in the absence of antibiotic and activated carbon. This effect was attributed to the enhanced retention of ERY, in comparison to NAL, on the surface of the activated carbon, probably due to its higher molecular size and affinity towards the activated carbon (log Kow = 3.06). This effect was more marked at low sludge retention times (below 8 days). Practitioner points: Ciprofloxacin (CIP), nalidixic acid (NAL), and erythromycin (ERY) were studied.NAL and ERY exerted negative impact on heterotrophic growth rate.Effect of antibiotics on microorganisms in the presence of activated carbon was studied.Activated carbon was mainly relevant for ERY due to its adsorption retention.Enhancement by activated carbon was more significant at low sludge retention times. [ABSTRACT FROM AUTHOR]

Aims This research focused on assessing the prevalence of plasmid-mediated quinolone resistance (PMQR) determinants and antimicrobial susceptibility in Salmonella strains isolated from Thai canal water. Methods and results From 2016 to 2020, 333 water samples were collected from six canals across Bangkok, Thailand. Salmonella spp. was isolated, PMQR genes were detected through polymerase chain reactions, and the antimicrobial susceptibility was examined using the disk diffusion method. The results indicated a 92.2% prevalence of Salmonella spp. in canal water, being serogroups B and C the most frequently detected. Overall, 35.3% of isolates harbored PMQR genes, being qnrS the most prevalent gene (97.2%, n  = 137/141). Other PMQR genes, including qnrB, qnrD, oqxAB , and aac(6′)-Ib-cr , were detected. Notably, six isolates harbored multiple PMQR genes. Furthermore, 9.3% and 3.8% of the overall isolates were resistant to nalidixic acid (NAL) and ciprofloxacin (CIP), respectively. PMQR-positive isolates showed higher rates of non-susceptibility to both NAL (48.2%, n  = 68/141) and CIP (92.2%, n  = 130/141) compared to PMQR-negative isolates (NAL: 8.9%, n  = 23/258; CIP: 11.2%, n  = 30/258). Conclusions The high prevalence of Salmonella spp. significant PMQR-positive, and reduced susceptibility isolates in canal water is of public health concern in Bangkok. [ABSTRACT FROM AUTHOR]

The Gram-negative anaerobe Fusobacterium nucleatum is a major producer of hydrogen sulfide (H2S), a volatile sulfur compound that causes halitosis. Here, we dissected the genetic determinants of H2S production and its role in bacterial fitness and virulence in this important member of the oral microbiome. F. nucleatum possesses four enzymes, CysK1, CysK2, Hly, and MegL, that presumably metabolize l-cysteine to H2S, and CysK1 was previously shown to account for most H2S production in vitro, based on correlations of enzymatic activities with gene expression at mid-log phase. Our molecular studies showed that cysK1 and megL were highly expressed at the late exponential growth phase, concomitant with high-level H2S production, while the expression levels of the other genes remained substantially lower during all growth phases. Although the genetic deletion of cysK1 without supplementation with a CysK1-catalyzed product, lanthionine, caused cell death, the conditional ΔcysK1 mutant and a mutant lacking hly were highly proficient in H2S production. In contrast, a mutant devoid of megL showed drastically reduced H2S production, and a cysK2 mutant showed only minor deficiencies. Intriguingly, the exposure of these mutants to various antibiotics revealed that only the megL mutant displayed altered susceptibility compared to the parental strain: partial sensitivity to nalidixic acid and resistance to kanamycin. Most significantly, the megL mutant was attenuated in virulence in a mouse model of preterm birth, with considerable defects in the spread to amniotic fluid and the colonization of the placenta and fetus. Evidently, the l-methionine γ-lyase MegL is a major H2S-producing enzyme in fusobacterial cells that significantly contributes to fusobacterial virulence and antibiotic susceptibility. IMPORTANCE Fusobacterium nucleatum is a key commensal anaerobe of the human oral cavity that plays a significant role in oral biofilm development and contributes to additional pathologies at extraoral sites, such as promoting preterm birth and colorectal cancer. Although F. nucleatum is known as a major producer of hydrogen sulfide (H2S), its genetic determinants and physiological functions are not well understood. By a combination of bacterial genetics, biochemical methods, and in vivo models of infection, here, we demonstrate that the l-methionine γ-lyase MegL not only is a major H2S-producing enzyme of F. nucleatum but also significantly contributes to the antibiotic susceptibility and virulence of this organism.

The increasing global incidence of quinolone antimicrobial resistance poses a considerable public health concern. The aquatic environment, particularly wastewater treatment plants (WWTPs), serves as a major reservoir for antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs), leading to the dissemination of antibiotic resistance. This study aimed to assess the prevalence and factors contributing to quinolone antibiotic resistance in Escherichia coli isolates obtained from effluents of 33 WWTPs. A total of 1082 E. coli isolates were analyzed, 32.6% and 17.1% of which showed resistance to nalidixic acid and ciprofloxacin, respectively. Phenotypic and genotypic analyses of antibiotic resistance demonstrated that quinolone resistance primarily originated from chromosomal mutations in the gyrA, parC, and parE genes, known as quinolone resistance-determining regions (QRDRs). The amino acid substitution at codon 83 in gyrA was closely associated with nalidixic acid resistance, whereas substitutions at codon 87 in gyrA and codon 80 in parC were significantly associated with ciprofloxacin resistance. The plasmid-mediated quinolone resistance (PMQR) genes qnrS and qnrB were identified in 41 isolates (11.5%) and 15 isolates (4.2%), respectively. Thus, we confirmed that the quinolone resistance in E. coli in WWTPs primarily occurs through QRDR mutations rather than through the acquisition of PMQR genes. Phylogenetic analysis revealed that most quinolone-resistant isolates belonged to the B1, A, B2, and D phylogenetic groups. Notably, the B2 group, which is responsible for extraintestinal infections, exhibited the highest rate of quinolone resistance. These findings provide novel insights into the presence and mechanisms of quinolone resistance in E. coli isolates from WWTPs, emphasizing the need for further research and understanding of quinolone resistance in the environment. [ABSTRACT FROM AUTHOR]

Bacterial cellulose (BC), a natural biopolymer is the purest form of cellulose produced by bacterial strains of the family Acetobateraceae. In this study, oleic acid (OA) and nalidixic acid (NA) was incorporated in BC deposited flax fabric (FF) produced through an in situ cultivation method with Gluconacetobacter liquefaciens (MTCC 3135). BC deposited FF were produced by using hydrosulphite of sodium (HS) medium and in presence of different amounts of honey (% w/w) as a suitable supplement. The sample produced through in situ cultivation method were designated as HS + xH (here, x and H represents the % value and honey, respectively). Maximum BC deposition of 9.43 ± 0.29% and 9.31 ± 0.19% was recorded for HS + 0H and HS + 4.5H, respectively. BC productivity was reduced significantly above 4.5% of honey content in the fermentation medium. Deposition of BC on FF with different morphology in presence of honey was confirmed by surface morphology as obtained by scanning electron microscopy (SEM). Fourier transform infrared spectroscopy (FTIR) analysis indicated that the deposition of BC showed no structural changes either in the presence or absence of honey. However, the X-ray diffraction (XRD) pattern showed a declining crystallinity index (CI) for deposited BC with an increasing percent of honey in the medium. CI for BC produced from HS + 0H was 76.98%, while it was 66.80% for HS + 4.5H. Similarly, mechanical characterization of BC deposited FF demonstrated tensile strength and Young's modulus of 38.66 MPa and 127.20 MPa in absence of honey as a supplement while 49.08 MPa and 181.01 MPa in presence of 1% honey. FTIR analysis for OA and NA incorporated in BC deposited FF shows the emergence of a new peak at 1715 cm−1. Further, antibacterial examination of OA and NA incorporated in BC deposited FF showed synergistic antibacterial activity against Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa with prolonged activity for more than one month. [ABSTRACT FROM AUTHOR]

This study introduces a series of novel Alkyl thio-1,2,4-triazole (4a-p) and mercapto-1,2,4-triazole (3a-d) compounds derived from nalidixic acid. The synthesis was streamlined, involving interactions between nalidixic acid hydrazide and various isothiocyanates to yield cyclic and alkyl(aryl) sulfide compounds, characterized using 1H NMR, 13C NMR, IR, and elemental analysis. Antioxidant capabilities were quantified through DPPH and ABTS assays, highlighting significant potential, especially for compound 3d, which demonstrated an ABTS IC50 value of 0.397 μM, on par with ascorbic acid (IC50 = 0.87 μM). Antibacterial efficacy was established through MIC assessments against a broad spectrum of Gram-positive and Gram-negative bacteria, including Candida albicans. Compounds 3b, 4e, 4h, 4j, 4i, 4m, and 4o showed broad-spectrum activity, with 4k and 4m exhibiting pronounced potency against E. coli. Molecular docking studies validated the antibacterial potential, with compounds 4f and 4h showing high binding affinities (docking scores of −9.8 and −9.6 kcal/mol, respectively), indicating robust interactions with the bacterial enzyme targets. These scores underscore the compounds' mechanistic basis for their antibacterial action and support their therapeutic promise. Furthermore, compounds 3b, 4i, and 4m, identified through drug-likeness and toxicity predictions, were highlighted for their favorable profiles, suggesting their suitability for oral antibiotic therapies. This comprehensive study, blending synthetic, in vitro, and in silico approaches, emphasizes the triazole derivatives' potential as future candidates for antibiotic and antioxidant applications, particularly spotlighting compounds 3b, 4i, and 4m due to their promising efficacy and safety profiles.

Emerging antibiotic contaminants in water is a global problem because bacterial strains resistant to these antibiotics arise, risking human health. This study describes the use of poly[(4-vinylbenzyl) trimethylammonium chloride] and N-alkylated chitosan, two cationic polymers with different natures and structures to remove nalidixic acid. Both contain ammonium salt as a functional group. One of them is a synthetic polymer, and the other is a modified artificial polymer. The removal of the antibiotic was investigated under various experimental conditions (pH, ionic strength, and antibiotic concentration) using the technique of liquid-phase polymer-based retention (LPR). In addition, a stochastic algorithm provided by Fukui's functions is used. It was shown that alkylated N-chitosan presents 65.0% removal at pH 7, while poly[(4-vinylbenzyl)trimethylammonium chloride] removes 75.0% at pH 9. The interaction mechanisms that predominate the removal processes are electrostatic interactions, π–π interactions, and hydrogen bonding. The polymers reached maximum retention capacities of 1605 mg g−1 for poly[(4-vinylbenzyl) trimethylammonium chloride] and 561 mg g−1 of antibiotic per gram for alkylated poly(N-chitosan). In conclusion, the presence of aromatic groups improves the capacity and polymer–antibiotic interactions. [ABSTRACT FROM AUTHOR]

In the present work, the conducted research concerned the determination of the toxicity and oxidative stress generation of the antidepressant fluoxetine (FLU), its metabolite nor-fluoxetine (Nor-FLU), the antibiotic nalidixic acid (NA), caffeic acid (CA) and their mixtures in three different environments: microbial medium (MM), raw wastewaters (RW) and treated wastewaters (TW). We evaluated the following parameters: E. coli cell viability, toxicity and protein damage, sodA promoter induction and ROS generation. It was found that FLU, Nor-FLU, NA, CA and their mixtures are toxic and they have the potency to generate oxidative stress in E. coli strains. We also detected that the wastewater, in comparison to the microbial medium, had an influence on the toxic activity and oxidative stress synthesis of the tested chemicals and their mixtures. Regardless of the environment under study, the strongest toxic activity and oxidative stress generation were detected after bacterial incubation with NA at a concentration of 1 mg/dm3 and the mixture of FLU (1 mg/dm3) with Nor-FLU (0.1 mg/dm3) and with NA (0.1 mg/dm3). The ROS synthesis and sodA promoter induction suggest that, in the case of the examined compounds and their mixtures, oxidative stress is the mechanism of toxicity. The analysis of the types of interactions among the substances constituting the mixtures in the wastewater revealed synergism, potentiation and antagonism. [ABSTRACT FROM AUTHOR]

The increasing global incidence of quinolone antimicrobial resistance poses a considerable public health concern. The aquatic environment, particularly wastewater treatment plants (WWTPs), serves as a major reservoir for antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs), leading to the dissemination of antibiotic resistance. This study aimed to assess the prevalence and factors contributing to quinolone antibiotic resistance in Escherichia coli isolates obtained from effluents of 33 WWTPs. A total of 1082 E. coli isolates were analyzed, 32.6% and 17.1% of which showed resistance to nalidixic acid and ciprofloxacin, respectively. Phenotypic and genotypic analyses of antibiotic resistance demonstrated that quinolone resistance primarily originated from chromosomal mutations in the gyrA, parC, and parE genes, known as quinolone resistance-determining regions (QRDRs). The amino acid substitution at codon 83 in gyrA was closely associated with nalidixic acid resistance, whereas substitutions at codon 87 in gyrA and codon 80 in parC were significantly associated with ciprofloxacin resistance. The plasmid-mediated quinolone resistance (PMQR) genes qnrS and qnrB were identified in 41 isolates (11.5%) and 15 isolates (4.2%), respectively. Thus, we confirmed that the quinolone resistance in E. coli in WWTPs primarily occurs through QRDR mutations rather than through the acquisition of PMQR genes. Phylogenetic analysis revealed that most quinolone-resistant isolates belonged to the B1, A, B2, and D phylogenetic groups. Notably, the B2 group, which is responsible for extraintestinal infections, exhibited the highest rate of quinolone resistance. These findings provide novel insights into the presence and mechanisms of quinolone resistance in E. coli isolates from WWTPs, emphasizing the need for further research and understanding of quinolone resistance in the environment.

"Drug repositioning" is a modern strategy used to uncover new applications for out-of-date drugs. In this context, nalidixic acid, the first member of the quinolone class with limited use today, has been selected to obtain nine new metal complexes with lanthanide cations (La3+, Sm3+, Eu3+, Gd3+, Tb3+); the experimental data suggest that the quinolone acts as a bidentate ligand, binding to the metal ion via the keto and carboxylate oxygen atoms, findings that are supported by DFT calculations. The cytotoxic activity of the complexes has been studied using the tumoral cell lines, MDA-MB-231 and LoVo, and a normal cell line, HUVEC. The most active compounds of the series display selective activity against LoVo. Their affinity for DNA and the manner of binding have been tested using UV–Vis spectroscopy and competitive binding studies; our results indicate that major and minor groove binding play a significant role in these interactions. The affinity towards serum proteins has also been evaluated, the complexes displaying higher affinity towards albumin than apotransferrin. [ABSTRACT FROM AUTHOR]

Emerging antibiotic contaminants in water is a global problem because bacterial strains resistant to these antibiotics arise, risking human health. This study describes the use of poly[(4-vinylbenzyl) trimethylammonium chloride] and N-alkylated chitosan, two cationic polymers with different natures and structures to remove nalidixic acid. Both contain ammonium salt as a functional group. One of them is a synthetic polymer, and the other is a modified artificial polymer. The removal of the antibiotic was investigated under various experimental conditions (pH, ionic strength, and antibiotic concentration) using the technique of liquid-phase polymer-based retention (LPR). In addition, a stochastic algorithm provided by Fukui’s functions is used. It was shown that alkylated N-chitosan presents 65.0% removal at pH 7, while poly[(4-vinylbenzyl)trimethylammonium chloride] removes 75.0% at pH 9. The interaction mechanisms that predominate the removal processes are electrostatic interactions, π–π interactions, and hydrogen bonding. The polymers reached maximum retention capacities of 1605 mg g−1 for poly[(4-vinylbenzyl) trimethylammonium chloride] and 561 mg g−1 of antibiotic per gram for alkylated poly(N-chitosan). In conclusion, the presence of aromatic groups improves the capacity and polymer–antibiotic interactions.

In the present work, the conducted research concerned the determination of the toxicity and oxidative stress generation of the antidepressant fluoxetine (FLU), its metabolite nor-fluoxetine (Nor-FLU), the antibiotic nalidixic acid (NA), caffeic acid (CA) and their mixtures in three different environments: microbial medium (MM), raw wastewaters (RW) and treated wastewaters (TW). We evaluated the following parameters: E. coli cell viability, toxicity and protein damage, sodA promoter induction and ROS generation. It was found that FLU, Nor-FLU, NA, CA and their mixtures are toxic and they have the potency to generate oxidative stress in E. coli strains. We also detected that the wastewater, in comparison to the microbial medium, had an influence on the toxic activity and oxidative stress synthesis of the tested chemicals and their mixtures. Regardless of the environment under study, the strongest toxic activity and oxidative stress generation were detected after bacterial incubation with NA at a concentration of 1 mg/dm3 and the mixture of FLU (1 mg/dm3) with Nor-FLU (0.1 mg/dm3) and with NA (0.1 mg/dm3). The ROS synthesis and sodA promoter induction suggest that, in the case of the examined compounds and their mixtures, oxidative stress is the mechanism of toxicity. The analysis of the types of interactions among the substances constituting the mixtures in the wastewater revealed synergism, potentiation and antagonism.

The possibility of adapting a chemical system for generating nitric oxide (NO) and superoxide anion (O2•−) upon the decomposition of 3-morpholinosydnonimine (SIN-1) in a buffer solution to the conditions of a similar experiment on bacterial cultures in the field of an MRI scanner was examined. For this system, the magnetic field effect on the recombination of the two radicals to form peroxynitrite (ONOO−) in a range of strong magnetic fields was experimentally found earlier and explained by the Δg mechanism. The transition from a model in vitro system involving biologically relevant species NO, O2•−, and ONOO− to an in vivo system and the development of a reliable model system with a reproducible magnetic field effect that can be employed as a working tool in further studies were considered. The decomposition of SIN-1 in the presence of components of an LB culture medium for bacterial cultures and the redox activity of the medium itself and a possible autoinitiation of the Fenton reaction on the intrinsic iron content were studied by spectrophotometry and ESR spectroscopy of spin traps. A decrease in the viability and formation of filaments for the E.coli JM109 strain were observed in experiments on the exposition of the bacterial strains in the presence of radical donors in a strong magnetic field of 11.7 T. [ABSTRACT FROM AUTHOR]

The human gut houses a complex group of bacterial genera, including both opportunistic pathogens and commensal micro‐organisms. These are regularly exposed to antibiotics, and their subinhibitory concentrations play a pivotal role in shaping the microbial responses. This study was aimed to investigate the effects exerted by sub‐MICs of nalidixic acid (NA) on the growth rate, bacterial motility, biofilm formation and expression of outer membrane proteins (OMPs) in a commensal strain of E. coli. The NA‐sensitive strain was sequentially passaged under sub‐MICs of NA. E‐test was used to determine the MIC values of NA. Results indicated significant changes in the growth profile of commensal E. coli upon exposure to NA at sub‐MICs. Differential expression of OMPs was observed in cells treated with sub‐MICs of NA. Bacterial motility was reduced under 1/2 MIC of NA. Interestingly, successive passaging under 1/2 MIC of NA led to the emergence of resistant E. coli with an increased MIC value of 64 µg ml−1 in just 24 days. The NA‐resistant variant was confirmed by comparing its 16S rRNA sequence to that of the sensitive commensal strain. Mutations in the Quinolone Resistance‐Determining Regions (QRDRs) of chromosomal gyrA, and Topoisomerase IV‐encoding parC genes were detected in NA‐resistant E. coli. Our results demonstrate how antibiotics play an important role as signalling molecules or elicitors in driving the pathogenicity of commensal bacteria in vitro. [ABSTRACT FROM AUTHOR]

“Drug repositioning” is a modern strategy used to uncover new applications for out-of-date drugs. In this context, nalidixic acid, the first member of the quinolone class with limited use today, has been selected to obtain nine new metal complexes with lanthanide cations (La3+, Sm3+, Eu3+, Gd3+, Tb3+); the experimental data suggest that the quinolone acts as a bidentate ligand, binding to the metal ion via the keto and carboxylate oxygen atoms, findings that are supported by DFT calculations. The cytotoxic activity of the complexes has been studied using the tumoral cell lines, MDA-MB-231 and LoVo, and a normal cell line, HUVEC. The most active compounds of the series display selective activity against LoVo. Their affinity for DNA and the manner of binding have been tested using UV–Vis spectroscopy and competitive binding studies; our results indicate that major and minor groove binding play a significant role in these interactions. The affinity towards serum proteins has also been evaluated, the complexes displaying higher affinity towards albumin than apotransferrin.

In this work, multi-walled carbon nanotubes were applied as sorbent for extraction, followed by back-extraction and HPLC/UV determination of Nalidixic acid in aqueous solutions. The effects of some parameters such as pH, flow velocity, sorbent amount, and ionic strength were investigated. A little amount of sorbent (5.0 mg) was chosen as its optimum amount which this sorbent was reusable for almost five cycles of adsorption/desorption processes. A preconcentration factor of 500 was obtained. Linear range was 0.19–23.2 mg L−1 (R2 = 0.9979). The limit of detection and RSD for the suggested method were 0.02 mg L−1 and 2.2%, respectively. To assess the method performance for real samples, Nalidixic acid was determined in human blood serum and tablet samples. Advantages of the suggested method for Nalidixic acid extraction and preconcentration are low cost, being less time consuming, simplicity, no usage of organic solvents, and high preconcentration factor and efficiency. [ABSTRACT FROM AUTHOR]

The present study was designed to detect resistant site of nalidixic acid through transformation and plasmid curing of S. aureus strains isolated from buffalo milk with subclinical mastitis and workers’ hands. A total of 37 S. aureus isolates including 17 isolates recovered from buffalo milk infected with subclinical mastitis, in addition to 20 isolates recovered from workers’ hands. All 37 isolates were investigated by detection of the 23S rRNA gene and various other species specific genes including coa, nuc and clfA. The antibiotic resistance of S. aureus isolates was performed by the discs diffusion method using 19 antibiotics. Plasmid transformation method was carried out by transferring the plasmid isolated from S. aureus into competent Escherichia coli HB 101 in order to detection the resistant site of nalidixic acid. Plasmid curing was accomplished by preparing different concentrations of nalidixic acid (100, 150, 200, 250 and 300 µg/ml) and cultured transformed E.coli on LB agar supported with each of the aforementioned concentrations. The molecular results showed that six isolates (five isolates from milk samples and one from workers’ hands) were identified as S. aureus by coa, nuc, and clfA species specific primers. The six S. aureus isolates were found to be resistant to at least 5 antibiotics which included the nalidixic acid. The results of plasmid transformation revealed that E. coli was able to grow on LB agar supported with 100µg/ml, 150 µg/ml, 200 µg/ml and 250 µg/mlof nalidixic acid and failed to grow on 300 µg/ml concentration.

Imidazolidine-2,4-diones (hydantoins and spirohydantoins) and nalidixic acid (1-ethyl-7-methyl-4-oxo-1,4- dihydro-1,8-naphthyridine-3-carboxylic acid) are heterocyclic compounds whose ring structures include nitrogen atoms. These substances exhibit potent pharmacological activity as antitumor, antibacterial and antifungal agents, as well as aldose reductase inhibitors. This article presents the synthesis of novel heterocyclic compounds, based on the interaction of imidazolidinediones with nalidixic acid. The imidazolidinedione derivatives obtained were characterized by physicochemical parameters, elemental analysis, IR, ¹H and 13C NMR spectral data. The biological activity of the synthesized products was evaluated against Gram-positive bacteria Staphylococcus aureus and Bacillus subtilis, Gram-negative bacteria Escherichia coli, Pseudomonas aeruginosa and Salmonella abony, the yeasts Candida albicans and Saccharomyces cerevisiae and the mold Aspergillus brasiliensis. All compounds showed activity against the Gram-positive and Gram-negative bacteria tested. [ABSTRACT FROM AUTHOR]

Nalidixic acid is a commonly prescribed treatment for suspected dysentery in Middle Eastern populations. We describe a case of convulsions resulting from a single dose of nalidixic acid in a previously healthy two-month-old child in Northern Iraq who was being treated for a diarrhoeal illness. The child presented to us with new onset seizures, irritability, and acidaemia. Nalidixic acid was thought to be responsible after the exclusion of other potential causes of seizures. Symptoms resolved by treatment with intravenous (IV) diazepam, and cessation of nalidixic acid, and the child recovered fully and was discharged home neurologically intact after two days of observation. In regions where it is commonly prescribed, such as Northern Iraq, nalidixic acid should be considered as a cause of convulsions in any seizing child who has been exposed to the drug. Furthermore, quinolones such as nalidixic acid are contraindicated in children < 3 months of age. [ABSTRACT FROM AUTHOR]

This study introduces a series of novel Alkyl thio-1,2,4-triazole ( 4a-p ) and mercapto-1,2,4-triazole ( 3a-d ) compounds derived from nalidixic acid. The synthesis was streamlined, involving interactions between nalidixic acid hydrazide and various isothiocyanates to yield cyclic and alkyl(aryl) sulfide compounds, characterized using 1H NMR, 13C NMR, IR, and elemental analysis. Antioxidant capabilities were quantified through DPPH and ABTS assays, highlighting significant potential, especially for compound 3d , which demonstrated an ABTS IC 50 value of 0.397 μM, on par with ascorbic acid (IC 50  = 0.87 μM). Antibacterial efficacy was established through MIC assessments against a broad spectrum of Gram-positive and Gram-negative bacteria, including Candida albicans . Compounds 3b , 4e , 4h , 4j , 4i , 4m , and 4o showed broad-spectrum activity, with 4k and 4m exhibiting pronounced potency against E. coli . Molecular docking studies validated the antibacterial potential, with compounds 4f and 4h showing high binding affinities (docking scores of -9.8 and -9.6 kcal/mol, respectively), indicating robust interactions with the bacterial enzyme targets. These scores underscore the compounds' mechanistic basis for their antibacterial action and support their therapeutic promise. Furthermore, compounds 3b , 4i , and 4m , identified through drug-likeness and toxicity predictions, were highlighted for their favorable profiles, suggesting their suitability for oral antibiotic therapies. This comprehensive study, blending synthetic, in vitro , and in silico approaches, emphasizes the triazole derivatives' potential as future candidates for antibiotic and antioxidant applications, particularly spotlighting compounds 3b , 4i , and 4m due to their promising efficacy and safety profiles., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

A molecularly imprinted polymer micro-solid phase extraction in pipette tip was employed for selective extraction and spectrophotometric determination of acetaminophen and nalidixic acid in pills and seawater samples. Parameters affecting microextraction, including pH of the sample, sample volume, type and elution solvent, number of cycles of extraction and desorption and amount of molecular imprinted polymer, were optimized utilizing both response surface methodology and one-variable-at-a-time methods. Four parameters in three levels were applied for response surface methodology experimental design. The proposed method indicated good linear range of 1.0–150.0 µg L−1 for nalidixic acid and 1.0–100.0 µg L−1 for acetaminophen by low detection limits of 0.2 and 0.3 µg L−1, respectively, for nalidixic acid and acetaminophen. Found recoveries were between 88.7 and 99.8% for real samples, with relative standard deviations less than 5.8%. The suggested protocol was successfully utilized to the separation, preconcentration and determination of nalidixic acid and acetaminophen in commercial pills and seawater samples. [ABSTRACT FROM AUTHOR]

Background and Objectives: Shigella is an etiological agent of shigellosis. Antibiotic therapy has a critical role in decreasing serious complications of shigellosis. The present study aimed to determine the multi-drug resistance strains and to detect fluoroquinolone related mutations. Materials and Methods: In this descriptive, cross sectional study, a total of 113 Shigella isolates were collected from 1280 patients admitted to Bu-Ali hospital in Ardabil province during 2015-17. Antibiotic resistance pattern of isolates was evaluated using Kirby Bauer method and finally, the MICs of ciprofloxacin were determined. In order to determine any mutations in QRDR region, parC and gyrA genes of resistant strains were amplified and sequenced. Results: Shigella spp. isolates were identified using ipaH amplification and rfc and wbgz genes were used for molecular detection of S. flexneri and S. soneii, respectively. Our results showed that the predominant species in Ardabil province was S. sonnei (69.91%). Most of isolates (82%) were resistant to trimethoprim/sulfamethoxazole (TMP/SMX); 51% were nalidixic acid resistant and 4.4% were floroquinolones resistant. All examined isolates were susceptible to imipenem (100%). Mutation in gyrA and parC genes were detected in all fluoroquinolone resistant isolates (5 isolates). Although, in this study the rate of resistance to ciprofloxacin was low, but in the lack of preventive strategy it will be a major challenge of public health in future. Conclusion: This study provided information on the prevalence and antimicrobial susceptibility patterns of Shigella isolates in Ardabil province, Iran. Also this study showed a high-level of resistance to commonly used antibiotics among Shigella isolates.

Abstract Resistance to quinolone antibiotics has been a serious problem ever since nalidixic acid was introduced into clinical medicine. Over time, resistance of pathogenic microbes to nalidixic acid led to the design of novel variants to revive its potential application. In the present work, a series of eight nanoformulations of nalidixic acid-based diacyl and sulfonyl acyl hydrazine derivatives were prepared. All nanoformulations were found to be stable at different storage temperatures. Antibacterial and anticandida activity of the eight nanoformulations presented encouraging results when compared with their non-nano parent counterparts. The nanoformulations of chloro, furanyl, and sulfonyl acyl substituted derivatives of nalidixic acid displayed most promising results (MIC ranging from 50 to 100 μg mL−1) against the tested bacteria and yeast. Among the screened bacteria, Acinetobacter baumannii displayed maximum sensitivity to the above nanoformulations. Biosafety study on the mammalian model—wax moth, Galleria mellonella—showed that all eight prepared nanoformulations were absolutely nontoxic to the larvae and subsequent pupae and hence may likely have no or low toxicity against mammalian systems. Graphical Abstract

Recent microcosm studies have revealed that fluoroquinolone (FQ) antibiotics can have ecotoxicological impacts on photosynthetic organisms, but little is known about the mechanisms of toxicity. We employed a combination of modeling and experimental techniques to explore how FQs may have these unintended secondary toxic effects. Structure-activity analysis revealed that the quinolone ring and secondary amino group typically present in FQ antibiotics may mediate their action as quinone site inhibitors in photosystem II (PS-II), a key enzyme in photosynthetic electron transport. Follow-up molecular simulations involving nalidixic acid (Naldx), a nonfluorinated quinolone with a demonstrated adverse impact on photosynthesis, and ciprofloxacin (Cipro), the most commonly used FQ antibiotic, showed that both may interfere stereochemically with the catalytic activity of reaction center II (RC-II), the pheophytin-quinone-type center present in PS-II. Naldx can occupy the same binding site as the secondary quinone acceptor (Q(B)) in RC-II and interact with amino acid residues required for the enzymatic reduction of Q(B). Cipro binds in a somewhat different manner, suggesting a different mechanism of interference. Fluorescence induction kinetics, a common method of screening for PS-II inhibition, recorded for photoexcited thylakoid membranes isolated from Cipro-exposed spinach chloroplasts, indicated that Cipro interferes with the transfer of energy from excited antenna chlorophyll molecules to the reaction center in RC-II ([Cipro] >or= 5 microM in vitro and >or=10 microM in vivo) and thus delays the kinetics of photoreduction of the primary quinone acceptor (Q(A); [Cipro] >or= 0.6 microM in vitro). Spinach plants exposed to Cipro exhibited severe growth inhibition characterized by a decrease in both the synthesis of leaves and growth of the roots ([Cipro] >or= 0.5 microM in vivo). Our results thus demonstrate that Cipro and related FQ antibiotics may interfere with photosynthetic pathways, in addition to causing morphological deformities in higher plants.

The discovery of new alternatives for the treatment of infectious diseases has become the focus of burgeoning global interest. The complexation of the wide-spectrum antibiotic nalidixic acid (NA) with oxidovanadium(IV) ion and its incorporation into hybrid nanoparticulate systems were explored. The V-NA complex proved to be a stronger antimicrobial agent against E. coli , B. cereus , S. aureus and P. aeruginosa than NA, based on inhibition experiments. Myristyl myristate nanostructured lipid carriers (NLCs) and polymeric nanoparticles of Eudragit NE30D (EuNPs) were hybridized with chitosan (chi) to increase their stability and mucoadhesivity. They showed V-NA encapsulation of 97.8 ± 0.5% and 96.1 ± 0.1% respectively. TEM and DLS characterization ascertained the presence of spherical positive charged NPs ranging from 170 to 330 nm. Controlled release of V-NA from NPs was observed with 30–40% release in 3 days. A considerable potentiation of V-NA antimicrobial activity from 5 to 10 times was elucidated against P. aeruginosa with MIC values of 59.3 and 129.9 μM for NLC/chi and EuNPs/chi respectively, in comparison with 625 μM of the free complex. Hybrid NPs were able to interfere with the quorum sensing of the reporter Chromobacterium violaceum. Cytotoxicity on mouse fibroblast L929 cells was evaluated in the range of 29.7–519 μM by MTT assay showing that, NLC/chi particles supported cell growth in the range of at 29.7–60 μM while Eu/chi do not exert cytotoxicity between 29.7 and 120 μM. These results suggest that nanoparticles are suitable systems for drug delivery applications. Unlabelled Image • The vanadium-nalidixic acid complex shows strong antibacterial activity. • Nanoencapsulation of V-NA into EuNPs and NLCs enhances its antibacterial properties. • Hybrid chitosan polymeric/lipidic matrices show a controlled release of V-NA. • V-NA loaded NLCs and EuNPs exhibit anti- quorum sensing properties. • V-NA EuNPs show great cytocompatibility in mouse fibroblast L929 cells at MICs values. [ABSTRACT FROM AUTHOR]

Glycerol plasticized soy protein isolate (SPI) films at different contents (1 to 5% w/w w.r.t SPI) of nalidixic acid (NA) were fabricated by solution casting method. SPI films and NA incorporated SPI films were structurally and mechanically characterized by Fourier transform infrared spectroscopy (FTIR) and mechanical properties, respectively. Thermomechanical and water uptake studies were also carried out for NA incorporated SPI films. The results from FTIR study indicated the presence of NA in SPI as evidenced by generation of two additional peaks at 1259 cm− 1 and 800 cm− 1 attributed to C–C stretching vibration and the deformation of the heterocyclic aromatic ring, respectively. At 4% NA, the tensile stress and tensile modulus of SPI films increased from 5.18 MPa to 8.57 MPa and 57.14 MPa to 93.90 MPa, respectively. Antibacterial activity of NA incorporated SPI films against E. coli and L. monocytogenes were studied. The antibacterial studies of NA incorporated SPI film showed the clear zone of inhibition against both the bacteria. Docking studies were performed for SPI in order to evaluate their binding affinity with NA and similar type of aromatic acids such as mandelic and benzilic acid with which SPI films have been prepared earlier by our group. After docking, the ligands in form of aromatic acids were evaluated according to their binding energy and the interaction pattern between SPI and aromatic acids. The docking results indicated that nitrogen containing heterocyclic ring moiety remained intact during interaction of SPI and NA. This work will be helpful in fabricating NA incorporated SPI film from the renewable resources with significant antibacterial properties and reasonable mechanical properties. [ABSTRACT FROM AUTHOR]

Objectives: To determine the mechanism of resistance to the antibiotic nitroxoline in Escherichia coli.Methods: Spontaneous nitroxoline-resistant mutants were selected at different concentrations of nitroxoline. WGS and strain reconstruction were used to define the genetic basis for the resistance. The mechanistic basis of resistance was determined by quantitative PCR (qPCR) and by overexpression of target genes. Fitness costs of the resistance mutations and cross-resistance to other antibiotics were also determined.Results: Mutations in the transcriptional repressor emrR conferred low-level resistance to nitroxoline [nitroxoline MIC (MICNOX)=16 mg/L] by increasing the expression of the emrA and emrB genes of the EmrAB-TolC efflux pump. These resistant mutants showed no fitness reduction and displayed cross-resistance to nalidixic acid. Second-step mutants with higher-level resistance (MICNOX=32-64 mg/L) had mutations in the emrR gene, together with either a 50 kb amplification, a mutation in the gene marA, or an IS upstream of the lon gene. The latter mutations resulted in higher-level nitroxoline resistance due to increased expression of the tolC gene, which was confirmed by overexpressing tolC from an inducible plasmid in a low-level resistance mutant. Furthermore, the emrR mutations conferred a small increase in resistance to nitrofurantoin only when combined with an nfsAB double-knockout mutation. However, nitrofurantoin-resistant nfsAB mutants showed no cross-resistance to nitroxoline.Conclusions: Mutations in different genes causing increased expression of the EmrAB-TolC pump lead to an increased resistance to nitroxoline. The structurally similar antibiotics nitroxoline and nitrofurantoin appear to have different modes of action and resistance mechanisms. [ABSTRACT FROM AUTHOR]

A novel compounds of nalidixic acid derivatives were synthesized by a coupling reaction with 2-aminothiazole-5-carbaldehyde using DIC as coupling reagent and HOBt as racemization suppressant then the product of reaction treated with different amine tail like 2-(methylthio) Ethan amine that result in compound 1 while refluxing with 2-(4-methyl piperazine-1-yl) Ethan amine and 2-(pyrrolidine-1-yl) Ethan amine results in compound 2 and 4 respectively. All the synthesized compounds were adequately identified by spectral studies utilizing IR and elemental analysis and assessed for their in vitro antibacterial activity in contradiction of different type of bacteria. All the tested molecules against bacterial strains compared with the nalidixic acid as a reference drug in this study. Results indicated that compounds 1, 2 & 4 have good antibacterial activities compared to standard drug especially as they were found to have promising activity against Bacillus and to be as effective as nalidixic acid toward psudomonus and E coli. [ABSTRACT FROM AUTHOR]

This article presents the synthesis of a series of amides, based on the interaction of several 3-aminospirohydantoins with nalidixic acid. The target compounds were characterized by physicochemical parameters, IR, 1H and 13C NMR spectral data. The antimicrobial activity of the products obtained was determined against Gram-positive bacteria Staphylococcus aureus and Bacillus subtilis, Gram-negative bacteria Escherichia coli, Pseudomonas aeruginosa and Salmonella abony, the yeasts Candida albicans and Saccharomyces cerevisiae and the molds Penicillium chrysogenum and Aspergillus niger. The relationship between structure and biological activity of the products obtained was discussed. It was found that the most effective compounds are tetralin (5f) and indane (5g) derivatives, which exhibit a pronounced antimicrobial activity against both tested Gram-positive and Gram-negative bacteria. [ABSTRACT FROM AUTHOR]

We use genetic assays to suggest that transcription-coupled repair or new origin formation in Escherichia coli involves removal of RNAP to create an RNA primer for DNA synthesis. Transcription factor DksA was shown to play a role in numerous reactions involving RNA polymerase. Some, but not all, of the activities of DksA at promoters or during transcription elongation require (p)ppGpp. In addition to its role during transcription, DksA is also involved in maintaining genome integrity. Cells lacking DksA are sensitive to multiple DNA damaging agents including UV light, ionizing radiation, mitomycin C, and nalidixic acid. Here, we focus on two recent studies addressing the importance of DksA in the repair of double-strand breaks (DSBs), one by Sivaramakrishnan et al. (Nature 550:214–218, 2017) and one originating in our laboratory, Myka et al. (Mol Microbiol 111:1382–1397. 10.1111/mmi.14227, 2019). It appears that depending on the type and possibly location of DNA damage, DksA can play either a passive or an active role in DSB repair. The passive role relies on exclusion of anti-backtracking factors from the RNAP secondary channel. The exact mechanism of active DksA-mediated DNA repair is unknown. However, DksA was proposed to destabilize transcription complexes, thus clearing the way for recombination and DNA repair. Based on the requirement for DksA, both in repair of DSBs and the R-loop-dependent formation of new origins of DNA replication, we propose that DksA may allow for removal of RNAP without unwinding of the RNA:DNA hybrid, which can then be extended by a DNA polymerase. This mechanism obviates the need for RNAP backtracking to repair damaged DNA. [ABSTRACT FROM AUTHOR]

Background and Objectives: Shigella is an etiological agent of shigellosis. Antibiotic therapy has a critical role in decreasing serious complications of shigellosis. The present study aimed to determine the multi-drug resistance strains and to detect fluoroquinolone related mutations. Materials and Methods: In this descriptive, cross sectional study, a total of 113 Shigella isolates were collected from 1280 patients admitted to Bu-Ali hospital in Ardabil province during 2015-17. Antibiotic resistance pattern of isolates was evaluated using Kirby Bauer method and finally, the MICs of ciprofloxacin were determined. In order to determine any mutations in QRDR region, parC and gyrA genes of resistant strains were amplified and sequenced. Results: Shigella spp. isolates were identified using ipaH amplification and rfc and wbgz genes were used for molecular detection of S. flexneri and S. soneii, respectively. Our results showed that the predominant species in Ardabil province was S. sonnei (69.91%). Most of isolates (82%) were resistant to trimethoprim/sulfamethoxazole (TMP/SMX); 51% were nalidixic acid resistant and 4.4% were floroquinolones resistant. All examined isolates were susceptible to imipenem (100%). Mutation in gyrA and parC genes were detected in all fluoroquinolone resistant isolates (5 isolates). Although, in this study the rate of resistance to ciprofloxacin was low, but in the lack of preventive strategy it will be a major challenge of public health in future. Conclusion: This study provided information on the prevalence and antimicrobial susceptibility patterns of Shigella isolates in Ardabil province, Iran. Also this study showed a high-level of resistance to commonly used antibiotics among Shigella isolates. [ABSTRACT FROM AUTHOR]

Nalidixic acid (NAL) is a broad-spectrum antimicrobial widely used for urinary tract infections. As demonstrated, complexation of NAL with Zn2+, Mn2+ and Cu2+ was often used to get new formulations with an enhanced efficiency and potency. Therefore, the elucidation of behavior of NAL in solution and of its interaction with metal cations are crucial to better understand the influence of complexation on NAL efficiency and to find the optimal conditions to propose novel formulations. As a preliminary study, spectrophotometric titrations were carried out on NAL to determine the values of the protonation constants and to define its acid-base behavior. Then, the interaction with the three metal cations Zn2+, Mn2+ and Cu2+ was investigated by potentiometric and spectrophotometric titrations, varying the conditions of temperature, ionic strength and metal-ligand ratio, thus allowing to get the most robust speciation model and to determine the formation constants with Zn2+, Mn2+, and Cu2+ under different conditions, the sequestering ability of NAL towards metal cations, the formation enthalpic and entropic changes. A simulation under serum conditions was reported to show the relevance of the investigated species. Finally, LD-MS (laser desorption ionization mass spectrometry) and MS/MS analyses highlighted for all systems the formation of the complex species between Zn2+, Mn2+ and Cu2+ with NAL. MS/MS investigations assigned the sites of coordination of the ligand with the metal cation. More precisely, deprotonated NAL coordinates the metal cation via the oxygens of the carboxylate and the carbonyl groups. Speciation diagram of nalidixic acid (L) in the presence of the serum main elelectrolytes vs. pH under serum conditions and pie diagram at pH = 7.4. [Display omitted] • Study on nalidixic acid complexation by a combination of different techniques. • Interaction of nalidixic acid with Zn2+, Mn2+, and Cu2+ under different conditions. • MS and MS/MS analyses to obtain information on the interaction mode. • Speciation diagram of nalidixic acid complex species under serum conditions. • Sequestering ability of nalidixic acid towards metal cations. [ABSTRACT FROM AUTHOR]

The objective of the study is to assess the sensitivity pattern of commonly isolated uropathogens towards the drugs Nitrofurontoin and Nalidixic acid. Widespread and irrational use of antibiotics has led to the development of highly resistant microorganisms. As the antibiotic sensitivity patterns of the microorganisms are frequently changing, this study was performed to assess the antibiotic sensitivity pattern of Nitrofurontoin and Nalidixic acid in urinary tract infections. This was a prospective, cross-sectional, observatory study conducted in the Department of Microbiology from January 2017 to July 2017 at RMMC, Chidambaram.300 culture positive urine samples were studied for the antibiotic susceptibility testing towards Nitrofurontoin and Nalidixic acid. The processing of the samples were done by standard microbiological methods. The antibiotic susceptibility was measured by disk diffusion test. CLSI guidelines were used for the antibiotic susceptibility evaluation[1]. Out of the 300 culture positive samples,the most common pathogen isolated in this study was E.coli(145),followed by Klebsiella(63), Staphylococcus aureus(35), Pseudomonas(36), Staphylococcus saprophyticus(10), Enterococcus(6), Sreptococcus(4), Proteus(1). The antibiotic susceptibility pattern for Nitrofurontoin : E.coli showed sensitivity (n=105) and resistance(40), Klebsiella showed sensitivity(47) and resistance(16), Staphylococcus aureus showed sensitivity(30) and resistance (5), Pseudomonas showed sensitivity(12) and resistance(24), Staphylococcus saprophyticus showed sensitivity(4) and resistance(2), Enterococcus showed sensitivity(5) and resistance (1), Streptococcus showed sensitivity (4) and resistance(0) and Proteus showed sensitivity (0) and resistance(1). The antibiotic susceptibility pattern for Nalidixic acid: E.coli showed sensitivity (n=23) and resistance(122), Klebsiella showed sensitivity(29) and resistance(43), Staphylococcus aureus showed sensitivity(9) and resistance (30), Pseudomonas showed sensitivity(4) and resistance(32), Staphylococcus saprophyticus showed sensitivity(2) and resistance(4), Enterococcus showed sensitivity(1) and resistance (5), Streptococcus showed sensitivity (0) and resistance(4) and Proteus showed sensitivity (0) and resistance(1). Urinary pathogens were more sensitive to Nitrofurontoin than Nalidixic acid. Klebsiella sp. was more sensitive towards Nitrofurontoin than E.coli. Hence Nitrofurontoin can be used as an effective drug in UTI.

Vibrio cholerae, as a natural inhabitant of the marine environment is among the world-leading causes of diarrheal diseases. The present study aimed to investigate the genetic relatedness of Iran 2012-2016 V. cholerae outbreaks with 7th pandemic cholera and to further characterize the non-ST69/non-ST75 sequence types strains by whole-genome sequencing (WGS).Twenty V. cholerae isolates related to 2012, 2013, 2015 and 2016 cholera outbreaks were studied by two genotyping methods - Pulsed-field Gel Electrophoresis (PFGE) and Multi-locus Sequence Typing (MLST)-and by antimicrobial susceptibility testing. Seven sequence types (STs) and sixteen pulsotypes were detected. Sequence type 69 was the most abundant ST confirming that most (65%, 13/20) of the studied isolates collected in Iran between 2012 and 2016 belonged to the 7th pandemic clone. All these ST69 isolates (except two) exhibited similar pulsotypes. ST75 was the second most abundant ST. It was identified in 2015 and 2016. ST438, ST178, ST579 and STs of 983 and 984 (as newfound STs) each were only detected in one isolate. All strains collected in 2016 appeared as distinct STs and pulsotypes indicative of probable different originations. All ST69 strains were resistant to nalidixic acid. Moreover, resistance to nalidixic acid, trimethoprim-sulfamethoxazole and tetracycline was only observed in strains of ST69. These properties propose the ST69 as a unique genotype derived from a separate lineage with distinct resistance properties. The circulation of V. cholerae ST69 and its traits in recent years in Iran proposes the 7th pandemic strains as the ongoing causes of cholera outbreaks in this country, although the role of ST75 as the probable upcoming dominant ST should not be ignored.Genomic analysis of non-ST69/non-ST75 strains in this study showed ST579 is the most similar ST type to 7th pandemic sequence types, due to the presence of wild type-El Tor sequences of tcpA and VC-1319, VC-1320, VC-1577, VC-1578 genes (responsible for polymyxin resistance in El Tor biotype), the traits of rstC of RS1 phage in one strain of this ST type and the presence of VPI-1 and VSP-I islands in ST579 and ST178 strains. In silico analysis showed no significant presence of resistance genes/cassettes/plasmids within non-ST69/non-ST75 strains genomes. Overall, these data indicate the higher susceptibility of V. cholerae non-ST69/non-ST75 strains in comparison with more ubiquitous and more circulating ST69 and ST75 strains.In conclusion, the occurrence of small outbreaks and sporadic cholera cases due to V. cholerae ST69 in recent years in Iran shows the 7th pandemic strains as the persistent causes of cholera outbreaks in this country, although the role of ST75 as the second most contributed ST should not be ignored. The occurrence of non-ST69/non-ST75 sequence types with some virulence factors characteristics in border provinces in recent years is noteworthy, and further studies together with surveillance efforts are expected to determine their likely route of transport., (© 2024. The Author(s).)

Campylobacter spp. are a leading cause of bacterial foodborne zoonosis worldwide, with poultry meat and products recognised as a significant source of human infection. In Vietnam there are few data regarding the occurrence, antimicrobial resistance, and genomic diversity of Campylobacter in poultry and poultry meat. The aim of this study was to estimate the prevalence of Campylobacter in chicken meat at retail in Hanoi, determine antimicrobial sensitivities of the Campylobacter isolated, and assess their genetic diversity. A total of 120 chicken meat samples were collected from eight traditional retail markets ( n =80) and four supermarkets ( n =40). Campylobacter was isolated following ISO 10272-1 : 2017 and identification verified by PCR. The prevalence of Campylobacter was 38.3 % (46/120) and C. coli was the most prevalent species in both retail markets (74 %) and supermarkets (88 %). The minimum inhibitory concentrations for ciprofloxacin, erythromycin, gentamicin, nalidixic acid, streptomycin, and tetracycline were determined by broth microdilution for 32 isolates. All characterised Campylobacter were resistant to ciprofloxacin, nalidixic acid, and tetracycline, with corresponding resistance determinants detected in the sequenced genomes. Most C. coli were multidrug resistant (24/28) and two harboured the erythromycin resistance gene ermB on a multiple drug-resistance genomic island, a potential mechanism for dissemination of resistance. The 32 isolates belonged to clonal complexes associated with both poultry and people, such as CC828 for C. coli . These results contribute to the One Health approach for addressing Campylobacter in Vietnam by providing detailed new insights into a main source of human infection and can inform the design of future surveillance approaches.

UDP-3- O- ( R -3-hydroxymyristoyl)- N -acetylglucosamine deacetylase (LpxC) is a zinc amidase that catalyzes the second step of the biosynthesis of lipid A, which is an outer membrane essential structural component of Gram-negative bacteria. Inhibitors of this enzyme can be attributed to two main categories, non-hydroxamate and hydroxamate inhibitors, with the latter being the most effective given the chelation of Zn 2+ in the active site. Compounds containing diacetylene or acetylene tails and the sulfonic head, as well as oxazoline derivatives of hydroxamic acids, are among the LpxC inhibitors with the most profound antibacterial activity. The present article describes the synthesis of novel functional derivatives of hydroxamic acids-bioisosteric to oxazoline inhibitors-containing 1,2,4- and 1,3,4-oxadiazole cores and studies of their cytotoxicity, antibacterial activity, and antibiotic potentiation. Some of the hydroxamic acids we obtained ( 9c , 9d , 23a , 23c , 30b , 36 ) showed significant potentiation in nalidixic acid, rifampicin, and kanamycin against the growth of laboratory-strain Escherichia coli MG1655. Two lead compounds ( 9c , 9d ) significantly reduced Pseudomonas aeruginosa ATCC 27853 growth in the presence of nalidixic acid and rifampicin.

Background: Enteric fever is a major public health problem in developing and under developed countries. Case fatality rate without treatment is 10-30% and with appropriate treatment is only 1-4%. Gold standard for diagnosis is isolation of Salmonella enterica from blood or bone marrow. Antibiotics resistance is skyrocketing with emergence of multidrug resistance S. typhi and extensively drug resistant S. typhi., Methods: The blood culture done in Kanti children hospital in last six years were taken from the data base and the culture positive cases were taken from which the salmonella species positive cases along with the drug sensitivity pattern were used in our study., Results: The culture positivity rate was 2.8% and 7.6% (n=136) among the culture positive cases were Salmonella species. Salmonella typhi (121; 88.9%) was the most frequently isolated species, followed by Salmonella paratyphi A (13; 9.5%) and Salmonella paratyphi B (2;1.4%). Children with age 5-10 years was the most affected age group for infection with Salmonella, 50.0% (n=68). Nalidixic acid is resistant in 89.9% Salmonella typhi; followed by ciprofloxacin (31.8%), ofloxacin (18.2%), ampicillin (9.6%), azithromycin (8.4%), chloramphenicol (8.2%), cotrimoxazole (5.4%), cefixime (4%), ceftriaxone (2.5%) and cefotaxime (0.0%). Cefixime, ceftriaxone, cefotaxime are 100% sensitive to Salmonella paratyphi, followed by cotrimoxazole (92.9%), ofloxacin (81.8%), chloramphenicol (75%), azithromycin (66.7%), ampicillin (60%), ciprofloxacin (50%) and Nalidixic acid (23.1%)., Conclusions: Salmonella species culture isolatation are declining every year. Fluoroquinolones have more resistance than first line drugs of typhoid, azithromycin resistance is rising but 3rd generation cephalosporins are sensitive to Salmonella species.

This study compared the antimicrobial resistance (AMR) of Escherichia coli detected from single samples vs. pooled samples at herd level. The national monitoring dataset included isolates from one sample per pig holding, whereas the research study included isolates from pooled samples of 10 pigs per holding. In both datasets, caecal samples were collected from healthy pigs randomly selected at slaughterhouses and plated on non-selective and antibiotic selective media. Resistance against a panel of nine antibiotics was compared between datasets by generalized linear mixed effects models (GLMMs) and by bootstrapped generalized linear model (GLM) to account for pooling. The highest proportion of resistant E. coli was observed against tetracycline and ampicillin in both datasets. In non-selective media, single and pooled samples showed similar results, but the bootstrapped GLM detected significantly lower resistance to ciprofloxacin and nalidixic acid in the national dataset. In selective media, a significantly greater proportion of resistant isolates was observed in the research dataset for ceftazidime (OR: 0.05, 95%CI = 0.01-0.42) and nalidixic acid (OR: 0.15, 95%CI = 0.05-0.51). The results suggest that one sample per holding provides similar information on AMR at herd level as pooled samples for most of the tested antibiotics, although less resistance to ciprofloxacin, ceftazidime, and nalidixic acid was detected., (© The Author(s) 2023. Published by Oxford University Press on behalf of Applied Microbiology International.)

In this study, a novel Schiff base (E)-1-ethyl-4-(2-hydroxyphenylimino)-7-methyl-1,4-dihydro-1,8 naphthyridine-3- carboxylic acid (H2L) was synthesized from nalidixic acid and 2-Aminophenol and it's complexes with metal ions M=VO, Mn, Co, Ni, Cu,Zn, Pd and Ptinethanolandacetic acid with moleratio(M:L)(1:2).All complexes have general composition ([VO (L)(H2O)], K2 [Mn(L)2]H2O, K2 [Co(L)2] H2O, K2 [Ni(L)2], [Zn(L) (H2O)], [Pd(KL)2] H2O, [Pt(KL)Cl2]) where: L- = C18H16N3O3. The ligand and all complexes were characterized by modern spectroscopic (FT-IR, UVVis, 1HNMR, Mass spectroscopy, atomic absorption), along with elemental microanalysis, magnetic susceptibility measurements, thermal analyses, chloride content and molar conductance. In addition to evaluated their biological activity against one type of bacterial and one type fungus. Based on date for all techniques we suggested that all the prepared complexes have octahedral geometry accept[Zn(L)(H2O)] tetrahedral geometry and [Pd(KL)2]H2OSquare planer geometry, [VO (L)(H2O)] square pyramidel. The value of antibacterial activity of this prepared complexes showed higher inhibition activity compared to the free ligand and starting material. [ABSTRACT FROM AUTHOR]

A series of new fluoroquinolone analogs (3–18) were prepared, in three steps, by substituting chloro esters and esters with cyclic amines on the C‐7 endo‐nortropine derivatives of difluoroquinolone acid. All the synthesized compounds displayed good MIC against the Staphylococcus aureus when initially screened for Escherichia coli, S. aureus, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa. The molecules were further evaluated for their antibacterial activity against fluoroquinolone‐resistant strains of S. aureus and for cytotoxic assay. Based on the results, five of the sixteen compounds displayed the potential to be developed further for treatment against fluoroquinolone‐resistant strains of S. aureus. [ABSTRACT FROM AUTHOR]