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BACKGROUND: Many diseases are increasingly recognized as public health concerns worldwide because of the increasing incidence of multidrug-resistant bacteria. Recently, interest in the use of indigenous medicinal plants to treat infectious illnesses has increased, highlighting the need to find new bioactive phytochemicals. Ajuga integrifolia is a plant commonly utilized in traditional drugs to treat a wide range of diseases, although its effectiveness has not been scientifically validated. The present study aimed to evaluate the total phenolic and flavonoid contents and assess the biological activities of A. integrifolia leaf extracts produced via different solvent systems. METHODS: Soxhlet extraction was employed to obtain crude extracts from different solvents (methanol, ethanol and water). The 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric-reducing power assays were used to measure the antioxidant activity, and the antibacterial activity of the extract was evaluated on the basis of its minimum inhibitory concentration (MIC) against two gram-negative bacteria (Escherichia coli (ATCC-25922) and Pseudomonas aeruginosa (ATCC-43495)) and two gram-positive bacteria (Staphylococcus aureus (ATCC-25923) and Streptococcus pyogenes (ATCC-19615)) via the agar disk-diffusion technique. RESULTS: A significant amount of total phenolic content (TPC) and flavonoid content (TFC) were present in all the extracts. The extracts presented powerful antioxidant activity in all the assays. The disc diffusion and MIC results revealed the ability of the methanol and ethanol extracts of A. integrifolia leaves to inhibit S. aureus growth at a concentration of 3.125 mg/mL. However, the water extracts were ineffective against E. coli and P. aeruginosa. CONCLUSIONS: These findings indicate that A. integrifolia leaf extracts have reasonable biological activities. These findings underscore the importance of A. integrifolia leaves as a source of health benefits.
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Ajuga , Antibacterianos , Antioxidantes , Testes de Sensibilidade Microbiana , Extratos Vegetais , Folhas de Planta , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Antibacterianos/farmacologia , Antioxidantes/farmacologia , Antioxidantes/química , Folhas de Planta/química , Ajuga/química , Solventes/química , Flavonoides/farmacologia , Fenóis/farmacologia , Fenóis/análiseRESUMO
Bacterial antimicrobial resistance (BAMR) seems to pose the greatest threat to public health, food safety, and agriculture in this century. The development of novel efficient antimicrobial agents to combat bacterial infections has become a global issue. Silver nanoparticles (Ag NPs) appeared as a feasible alternative to antibiotics. However, Ag NPs face cost, toxicity, and aggregation issues which limit their antibacterial activity. This work aims to stabilize Ag NPs with enhanced antimicrobial activity at comparatively lower Ag concentrations to prevent bacterial infections. For this purpose, the Ag core was covered with nanodiamonds (NDs). Ag-NDs composite have been synthesized by microplasma technique. TEM analysis confirmed the presence of both Ag and NDs in the Ag-NDs composite. A particle size (â¼19 nm) was reported for Ag-NDs at the highest concentration as compared to Ag NPs (â¼3 nm). The conduction band of the diamond acted as an extremely strong reducing agent for Ag NPs. The large surface area of NDs stabilized the Ag NPs. A redshift (â¼400 nm-406 nm) in UV-visible spectra of the Ag-NDs composite indicated the formation of bigger-sized Ag NPs after incorporating NDs. XRD and LIBS analysis verified the increase in intensity of Ag-NPs by increasing ND concentration. The presence of functional groups including OH, CH, and Ag/Ag2O was confirmed by FTIR. Bacterial inhibition growth appeared to be a dose-dependent process. The minimum inhibition concentration value of Ag-NDs composite at the highest NDs concentration against E. coli (â¼ 0.69 µg/ml) and S. aureus (â¼44 µg/ml). This is the first study to report the smallest MIC for E. coli (<1 µg/ml). Ag-ND composites emerged to be more efficient than Ag NPs and preferred to be used against BAMR. The enhanced antibacterial activity of the Ag-NDs composite makes it a potential candidate for antibiotics, food products, and pesticides.
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To tackle the proliferation of pathogenic microorganisms without relying on antibiotics, innovative materials boasting antimicrobial properties have been engineered. This study focuses on the development of graphene oxide/silver (GO/Ag) nanocomposites, derived from partially reduced graphene oxide adorned with silver nanoparticles. Various nanocomposites with different amounts of silver (GO/Ag-1, GO/Ag-2, GO/Ag-3, and GO/Ag-4) were synthesized, and their antibacterial efficacy was systematically studied. The silver nanoparticles were uniformly deposited on the partially reduced graphene oxide surface, exhibiting spherical morphologies with an average size of 25 nm. The nanocomposites displayed potent antibacterial properties against both gram-positive bacteria (S. aureus and B. subtilis) and gram-negative bacteria (E. coli and S. enterica) as confirmed by minimum inhibition concentration (MIC) studies and time-dependent experiments. The optimal MIC for Gram-positive bacteria was 62.5 µg/mL and for Gram-negative bacteria was 125 µg/mL for the GO/Ag nanocomposites. Bacterial cells that encountered the nanocomposite films exhibited significantly greater inhibitory effects compared to those exposed to conventional antibacterial materials. Furthermore, the cytotoxicity of these nanocomposites was assessed using human epithelial cells (HEC), revealing that GO/Ag-1 and GO/Ag-2 exhibited lower toxicity levels toward HEC and remained compatible even at higher dilution rates. This study underscores the potential of GO/Ag-based nanocomposites as versatile materials for antibacterial applications, particularly as biocompatible wound dressings, offering promising prospects for wound healing and infection control.
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Grafite , Nanopartículas Metálicas , Nanocompostos , Humanos , Prata/farmacologia , Staphylococcus aureus , Escherichia coli , Óxidos/farmacologia , Antibacterianos/farmacologia , Grafite/farmacologiaRESUMO
OBJECTIVES: Patients with Mycobacterium avium complex-pulmonary disease (MAC-PD) can exhibit contraindications in applying the recommended treatment regimens by the guidelines. Clofazimine (CFZ) is considered a promising drug for MAC-PD treatment and is frequently included in alternative regimens; however, its efficacy remains unclear. METHODS: MAC-PD patients, unsuitable for standard regimens, were enrolled continuously in a prospective study at Beijing Chest Hospital. The treatment response of the CFZ-containing regimen was monitored. RESULTS: Fifty patients were enrolled in the initial treatment, and 25 patients had a history of anti-TB treatment. Nodular bronchiectasis was observed in 34 patients, while 8 patients exhibited fibrocavitary changes. Additionally, eight patients displayed a combination of both patterns. In a multivariate analysis, MAC-PD patients with CFZ MIC < 0.25 mg/L were significantly associated with culture conversion [OR 8.415, 95% CI (1.983-35.705); P = 0.004]. Among patients who had previous TB treatment history, patients with CFZ MIC < 0.25 mg/L had a higher chance of acquiring culture conversion outcomes [(OR 7.737, 95% CI 1.032-57.989); P = 0.046]. In contrast, among patients with no previous TB treatment history, the RIF-containing regimen had a higher chance of acquiring culture conversion outcomes [(OR 11.038, 95%CI 1.008-120.888); P = 0.049]. CONCLUSION: MAC-PD patients unsuitable for standard regimens could benefit from a CFZ-containing regimen, especially for patients with previous TB treatment history and baseline CFZ MIC values lower than 0.25 mg/L.
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Pneumopatias , Infecção por Mycobacterium avium-intracellulare , Humanos , Clofazimina/uso terapêutico , Complexo Mycobacterium avium , Infecção por Mycobacterium avium-intracellulare/tratamento farmacológico , Estudos Prospectivos , Quimioterapia Combinada , Pneumopatias/tratamento farmacológico , Antibacterianos/uso terapêuticoRESUMO
In this study, bacterial ghosts (BGs) were generated from Weissella koreensis LKS42 (WKorGs) and Pediococcus pentosacues KA94 (PPGs) by chemically inducing lysis using substances such as hydrochloric acid (HCl), sulfuric acid (H2SO4), nitric acid (HNO3), acetic acid (CH3COOH), sodium hydroxide (NaOH), potassium hydroxide (KOH), sodium carbonate (Na2CO3), n-butanol, and C6H8O7. HCl-induced WKorGs and PPGs exhibited complete removal of DNA and displayed transverse membrane dissolution tunnel structures under scanning electron microscopy (SEM). Cell viability assays showed high viability of RAW 264.7 cells exposed to HCl-induced WKorGs and PPGs. Additionally, treatment with HCl-induced WKorGs and PPGs elevated mRNA levels of pro-inflammatory cytokines (IL-1ß, IL-6, TNF-α, iNOS) and the anti-inflammatory cytokine IL-10 in RAW 264.7 cells. These findings suggest that HCl-induced WKorGs and PPGs have the potential to be used as inactivated bacterial immunostimulants, highlighting their promising applications in immunization and immunotherapy.
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Adjuvantes Imunológicos , Weissella , Adjuvantes Imunológicos/farmacologia , Pediococcus pentosaceus , Imunização , CitocinasRESUMO
In the present study, the individual cultures of Proteus mirabilis (P. mirabilis) and Klebsiella pneumoniae (K. pneumoniae) were treated with morphologically modified silver nanoparticles (Ag NPs) and were found to display zones of inhibition of ~ 8 mm, 16 mm, 20 mm, and 22 mm (P. mirabilis) and 6 mm, 14 mm, 20 mm, and 24 mm (K. pneumoniae) at concentrations of 25 µg/ml, 50 µg/mL, 75 µg/mL, and 100 µg/mL, respectively. In addition, turbidity tests were performed based on O. D. values, which exhibited 92% and 90% growth inhibitions at 100 µg/mL concentration for P. mirabilis and K. pneumoniae, respectively. Furthermore, the IC50 concentration of Ag NPs was established for A549 lung cancer cells and found to be at 500 µg/mL. Evidently, the morphological variation of Ag NPs treated A549 lung cancer cells was exhibited with differential morphology studied by phase-contrast microscopy. The results demonstrated that the synthesized Ag NPs was not only efficient against gram-positive bacteria but also against gram-negative bacteria and A549 cancer cells, suggesting that the potential of these biosynthesized Ag NPs is a future drug discovery source for inhibiting bacteria and cancer cells.
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Neoplasias Pulmonares , Nanopartículas Metálicas , Humanos , Prata/farmacologia , Descoberta de Drogas , Klebsiella pneumoniae , Proteus mirabilisRESUMO
<b>Background and Objective:</b> <i>Kalanchoe tomentosa</i> is identified and their different characteristics regarding the antibacterial and antioxidant properties have a vast effect. Fresh <i>K. tomentosa</i> leaves obtained from Bandung, Indonesia was extracted using n-hexane followed by serial dichloromethane maceration. <b>Materials and Methods:</b> N-hexane and ethyl acetate were used to separate the dichloromethane extract using vacuum liquid chromatography and the isolated compounds were recrystallized with n-hexane. <b>Results:</b> About 37 mg of dichloromethane extract was obtained from the extraction process. Recrystallized compound isolates were identified as stigmast-5-en-3-ol or ß-sitosterol. Both dichloromethane extract and ß-sitosterol isolated compounds showed strong bacteriostatic activity against <i>S. aureus</i> with MIC = 15.63 and 7.81 µg mL<sup></sup><sup>1</sup> and<i> K. pneumonia</i> with MIC = 7.81 and 31.25 µg mL<sup></sup><sup>1</sup>, respectively. However, only dichloromethane extract exhibited a bactericidal effect (7.81 µg mL<sup></sup><sup>1</sup>). <b>Conclusion:</b> The pure ß-sitosterol compound was isolated from<i> K. tomentosa</i> dichloromethane extract. Both the dichloromethane extract and the isolated ß-sitosterol compound had antibacterial effects against <i>S. aureus</i> and <i>K. pneumonia.</i>.
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Kalanchoe , Pneumonia , Antibacterianos/química , Antibacterianos/farmacologia , Klebsiella , Cloreto de Metileno , Extratos Vegetais/química , Folhas de Planta/química , Sitosteroides , Staphylococcus aureusRESUMO
Mycoplasma salivarium, an oral commensal organism, can cause severe invasive infections in immunocompromised individuals. Currently there is no treatment guidance for such infections. We performed antimicrobial susceptibility tests on 39 commensal and invasive M. salivarium isolates and investigated the mechanisms of antimicrobial resistance. Clindamycin was the most active agent [minimum inhibition concentration (MIC) range: 0.004-128 mg/L, MIC50 = 0.031 mg/L, MIC90 = 0.125 mg/ml], followed by tetracycline and levofloxacin. All isolates were resistant to erythromycin (MIC ≥4 mg/L) due to the presence of 2057A (Escherichia coli numbering) in 23S rRNA. Three isolates with elevated clindamycin MICs (≥8 mg/L) harbored A2058T/G mutations in 23S rRNA gene; four sequential isolates from one patient developed C2611T and A2059G mutations accompanying the increase of clindamycin MICs. Five isolates with elevated tetracycline MICs (≥4 mg/L) had mutations in 16S rRNA gene (A965G/T, G966T, or A967C/T) and one of them harbored TetM. Nine isolates with elevated levofloxacin MICs (≥4 mg/L) had one or more mutations in gyrA, gyrB, parC, or parE. Susceptibility breakpoints for clindamycin, tetracycline and levofloxacin were suggested to be ≤0.125, ≤2, and ≤2 mg/L, respectively. Antimicrobial resistance to any of the three agents (clindamycin, tetracycline, or levofloxacin) was documented in 12 (34.3%) non-duplicate isolates, of which 10 were invasive. Levofloxacin resistance was most frequent (25.7%). Multi-drug resistance was also observed (14.3%). This study demonstrates the frequent occurrence of antimicrobial resistance in M. salivarium, emphasizing the need for culture and susceptibility testing to guide antimicrobial therapy.
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This study aimed to evaluate the antibacterial activity in vitro of Salpianthus macrodontus and Azadirachta indica extracts against potentially pathogenic bacteria for Pacific white shrimp. Furthermore, the extracts with higher inhibitory activity were analyzed to identify compounds responsible for bacterial inhibition and evaluate their effect on motility and biofilm formation. S. macrodontus and A. indica extracts were prepared using methanol, acetone, and hexane by ultrasound. The minimum inhibitory concentration (MIC) of the extracts was determined against Vibrio parahaemolyticus, V. harveyi, Photobacterium damselae and P. leiognathi. The polyphenol profile of those extracts showing the highest bacterial inhibition were determined. Besides, the bacterial swimming and swarming motility and biofilm formation were determined. The highest inhibitory activity against the four pathogens was found with the acetonic extract of S. macrodontus leaf (MIC of 50 mg/mL for Vibrio spp. and 25 mg/mL for Photobacterium spp.) and the methanol extract of S. macrodontus flower (MIC of 50 mg/mL for all pathogens tested). Both extracts affected the swarming and swimming motility and the biofilm formation of the tested bacteria. The main phenolic compounds related to Vibrio bacteria inhibition were naringin, vanillic acid, and rosmarinic acid, whilst hesperidin, kaempferol pentosyl-rutinoside, and rhamnetin were related to Photobacterium bacteria inhibition.
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Penaeidae , Vibrio parahaemolyticus , Animais , Antibacterianos/farmacologia , Metanol , Testes de Sensibilidade Microbiana , Extratos Vegetais/farmacologiaRESUMO
Antimicrobial stewardship is imperative when treating bacterial infections because the misuse and overuse of antibiotics have caused pathogens to develop life-threatening resistance mechanisms. The New Delhi metallo-beta-lactamase (NDM-1) is one of many enzymes that enable bacterial resistance. NDM-1 is a more recently discovered beta-lactamase with the ability to inactivate a wide range of beta-lactam antibiotics. Multiple NDM-1 inhibitors have been designed and tested; however, due to the complexity of the NDM-1 active site, there is currently no inhibitor on the market. Consequently, an infection caused by bacteria possessing the gene for the NDM-1 enzyme is a serious and potentially fatal complication. An abundance of research has been invested over the past decade in search of an NDM-1 inhibitor. This review aims to summarize various NDM-1 inhibitor designs that have been developed in recent years.
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Antibacterianos/farmacologia , Infecções Bacterianas/tratamento farmacológico , Desenho de Fármacos , Inibidores de beta-Lactamases/farmacologia , beta-Lactamases/metabolismo , Antibacterianos/síntese química , Antibacterianos/química , Infecções Bacterianas/metabolismo , Humanos , Estrutura Molecular , Inibidores de beta-Lactamases/síntese química , Inibidores de beta-Lactamases/químicaRESUMO
Koumiss has beneficial therapeutic effects on bacterial diseases. Four antibacterial com- pounds from yeasts (Kluyveromyces marxianus and Saccharomyces cerevisiae) in koumiss were evaluated for their antibacterial effects against three Gram-negative bacteria, three Gram-positive bacteria and five pathogenic Escherichia coli strains. The antibacterial compounds from yeasts in koumiss were extracted, and their main components were determined. The inhibition zones were analyzed, and their minimum inhibition concentrations (MICs) and minimum bactericidal concentrations (MBCs) were determined. Aqueous phases of Kluyveromyces marxianus and Saccharomyces cerevisiae at pH 2.0 and 8.0 produced larger inhibition zones than those in other phases, and then antibacterial compounds from K. marxianus (K2, pH=2.0; K8, pH=8.0) and S. cerevisiae (S2, pH=2.0; S8, pH=8.0) were obtained. Their main components were organic acids and killer toxins. K2 had more propanoic acid and S2 had more oxalic acid than others. The inhibition zones of K2, K8, S2 and S8 against three Gram-negative bacteria and three Gram-positive bacteria were 12.03-23.30 mm, their MICs were 0.01-0.13 g/mL, and MBCs were 0.03-0.50 g/mL. Meantime, the inhibition zones of K2, K8, S2 and S8 against five pathogenic E. coli were 16.10-25.26 mm, their MICs were 0.03-0.13 g/mL, and MBCs were 0.13-1.00 g/mL. These four antibacterial compounds from yeasts in koumiss had broad antibacterial spectrum. In addition, K2 and S2 were better than K8 and S8.
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Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Kumis/microbiologia , Leveduras/metabolismo , Antibacterianos/química , Leveduras/químicaRESUMO
The multi-drug resistant effect of the Gram negative bacteria K. pneumoniae was identified by disc diffusion method using specific UTI panel discs of Kleb 1 HX077 and Kleb 2 HX090 HEXA. Among the multi-drug resistant bacteria, the carbapenem resistant (CR) effect of the K. pneumoniae was screened by specific carbapenem detection antibiotics of HEXA HX066 and HX0103 HEXA by disc diffusion method. In addition, the effective antibiotics were further performed against K. pneumoniae by minimum inhibition concentration method. Further, the carbapenemase genes of VIM 1 and IMP 1 were detected from the isolated strains by multiplex PCR method. Furthermore, the biofilm forming ability of selected carbapenem resistant K. pneumoniae was initially identified by tissue culture plate method and confirmed by exopolysaccharide arrest ability of congo red agar assay. Finally, our result was proved that the identified K. pneumoniae is carbapenemase producing strain, and its virulence was extended with strong biofilm formation.
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In this study, the phytochemical, phenolic, flavonoid and bioactive compounds were successfully screened from crude extract of Sargassum wightii by LC-MS analysis after NIST interpretation. Bacterial growth inhibition study result was shown with 24 mm zone inhibition at 200 µg/mL concentration against P. aeruginosa. The increased phenolic content was much closed to gallic acid and the range was observed at 250 µg/mL concentration. In addition, flavonoid contents of the algae extract was indicated more significant with rutin at 200 µg/mL. In result, both the phenolic and flavonoid contents of the extract were more correlated with gallic acid and rutin. Further, the total anti-oxidant and DPPH radical scavenging activities were shown increased activity at 200 µg/mL concentrations. Furthermore, the excellent anti-bacterial alteration result was observed at 200 µg/mL concentration by minimum inhibition concentration. Therefore, the result was revealed that the marine algae Sargassum wightii has excellent phytochemical and anti-oxidant activities, and it has improved anti-bacterial activity against P. aeruginosa.
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The development of antibiotic resistant in K. pneumoniae is an emerging thread worldwide due to the poor antimicrobial drugs. To overcome this issue, researchers are focused on plant material and their essential oils to fight against multi drug resistant bacteria. In this context, the current study was concentrated in medicinal plant of guva leaves and their essential oils to combat multi drug resistant bacterial infections. The essential oils were successfully screened and confirmed by HRLC-MS analysis. The anti-bacterial ability of the compounds were loaded into the chitosan nanoparticles and proved by FT-IR analysis. In addition, the chitosan loaded essential oils morphology was compared with chitosan alone in SEM analysis and suggested that the material was loaded successfully. Further, the anti-bacterial ability of the chitosan loaded essential oils were primarily confirmed by agar well diffusion method. At the 100 µg/mL of lowest concentration of chitosan loaded essential oils, the multi-drug resistant K. pneumoniae was inhibited with 96% and confirmed by minimum inhibition concentration experiment. Hence, all the experiments were proved that the essential oils were successfully loaded into the chitosan nanoparticles, and it has more anti-bacterial activity against multi-drug resistant K. pneumoniae.
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Minimum inhibition concentration (MIC) of antibiotic is an effective value to ascertain the agent and minimum dosage of inhibiting bacterial growth. However, current techniques to determine MIC are labor intensive and time-consuming, and require skilled operator and high initial concentration of bacteria. To simplify the operation and reduce the time of inhibition test, we developed a microfluidic system, containing a concentration generator and sub-micro-liter chambers, for rapid bacterial growth and inhibition test. To improve the mixing effect, a micropillar array in honeycomb-structure channels is designed, so the steady concentration gradient of amoxicillin can be generated. The flanged chambers are used to culture bacteria under the condition of continuous flow and the medium of chambers is refreshed constantly, which could supply the sufficient nutrient for bacteria growth and take away the metabolite. Based on the microfluidic platform, the bacterial growth with antibiotic inhibition on chip can be quantitatively measured and MIC can be obtained within six hours using low initial concentration of bacteria. Overall, this microfluidic platform has the potential to provide rapidness and effectiveness to screen bacteria and determine MIC of corresponding antibiotics in clinical therapies.
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BACKGROUND: Burn is still an important global public health challenge. Wound colonization of antibiotic resistant bacteria such as Acinetobacter baumannii can lead to high morbidity and mortality in burn patients. The aim of this study was to evaluate the inhibitory effect of tazobactam on efflux pump, which can cause aminoglycoside resistant in A. baumannii isolated from burn patients. METHODS: In this study, 47 aminoglycoside resistant A. baumannii spp. were obtained from burn patients, admitted to the Shahid Motahari Burns Hospital in Tehran, Iran, during June-August 2018. The inhibitory effect of tazobactam against adeB such as efflux pump was evaluated by Minimum Inhibitory Concentration (MIC) determination of amikacin alone and in combination with tazobactam. Fractional Inhibitory Concentration index (FIC) was used to determine the efficacy of tazobactam/ amikacin combination. Further, semi-quantitative Real- Time PCR was performed to quantify the expression rates of the adeB gene before and after addition of tazobactam/amikacin. RESULTS: The MIC values were significantly reduced when a combined amikacin and tazobactam was utilized. The most common interaction observed was synergistic (78.2%), followed by.additive effects (21.8%), as per FIC results. The adeB mRNA expression levels were found to be downregulated in 60.7% of isolates treated with tazobactam. CONCLUSION: Tazobactam can have impact on resistance to aminoglycoside by inhibiting efflux pump. Thus, the combination of tazobactam with amikacin can be used as an alternative treatment approach in multidrug resistant A. baumannii infections.
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Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/efeitos dos fármacos , Amicacina/farmacologia , Antibacterianos/farmacologia , Queimaduras/microbiologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Tazobactam/farmacologia , Infecções por Acinetobacter/tratamento farmacológico , Acinetobacter baumannii/genética , Acinetobacter baumannii/isolamento & purificação , Queimaduras/tratamento farmacológico , Farmacorresistência Bacteriana Múltipla/genética , Sinergismo Farmacológico , Genes Bacterianos , Humanos , Irã (Geográfico) , Testes de Sensibilidade MicrobianaRESUMO
Multidrug membrane transporters exist in both prokaryotic and eukaryotic cells, which causes multidrug resistance (MDR) and urgent need of new and more effective therapeutic agencies. In this study, we used three different sized antibiotic nanocarriers to study their mode of actions and their size-dependent inhibitory effects against Escherichia coli (E. coli). The antibiotic nanocarriers (AgMUNH-Oflx NPs) with 8.6×102, 9.4×103 and 6.5×105 Oflx molecules per nanoparticle (NP) were prepared by functionalizing the Ag NPs (2.4 ± 0.7, 13.0 ± 3.1 and 92.6 ± 4.4 nm) with a monolayer of 11-amino-1-undecanethiol (MUNH2) and covalently linking ofloxacin (Oflx) with the amine group of AgMUNH2 NPs, respectively. We designed a modified cell culture medium for nanocarriers to be stable (non-aggregated) over 18 h of cell culture, which enables us to quantitatively study their size and dose dependent inhibitory effects against E. coli. We found that inhibitory effects of Oflx against E. coli highly depend upon dose of Oflx and size of nanocarriers, showing that the equal amount of Oflx delivered by the largest nanocarriers (92.6 ± 4.4 nm) were the most potent with the lowest minimum inhibitory concentration (MIC50) and created the longest and highest percentage of filamentous cells, while the smallest nanocarriers (2.4 ± 0.7) were the least potent with the highest MIC50 and produced the shortest and lowest percentage of filamentous cells. Interestingly, the same amount of Oflx on 2.4 ± 0.7 nm nanocarriers showed the 2x higher MIC and created the 2x shorter filamentous cells than free Oflx, while the Oflx on 13.0 ± 3.1 and 92.6 ± 4.4 nm nanocarriers exhibited 2x and 6x lower MICs, and produced 2x and 3x longer filamentous cell than free Oflx, respectively. Notably, three sized AgMUNH2 NPs (absence of Oflx) showed negligible inhibitory effects and did not create filamentous cells. The results show that the filamentation of E. coli highly depends upon the sizes of nanocarriers, which leads to the size-dependent inhibitory effects of nanocarriers against E. coli.
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Candida albicans is a major fungal pathogen, accounting for approximately 15% of healthcare infections with associated mortality as high as 40% in the case of systemic candidiasis. Antifungal agents for C. albicans infections are limited, and rising resistance is an inevitable problem. Therefore, understanding the mechanism behind antifungal responses is among the top research focuses in combating Candida infections. Herein, the recently developed C. albicans haploid model is employed to examine the association between mitochondrial fission, regulated by Dnm1, and the pathogen's response to antifungals. Proteomic analysis of dnm1Δ and its wild-type haploid parent, GZY803, reveal changes in proteins associated with mitochondrial structures and functions, cell wall, and plasma membrane. Antifungal susceptibility testing revealed that dnm1Δ is more susceptible to SM21, a novel antifungal, than GZY803. Analyses of reactive oxygen species release, antioxidant response, lipid peroxidation, and membrane damages uncover an association between dnm1Δ and the susceptibility to SM21. Dynasore-induced mitochondrial inhibition in SC5314 diploids corroborate the findings. Interestingly, Dynasore-primed SC5314 cultures exhibit increased susceptibility to all antifungals tested. These data suggest an important contribution of mitochondrial fission in antifungal susceptibility of C. albicans. Hence, mitochondrial fission can be a potential target for combined therapy in anti-C. albicans treatment.
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Antifúngicos/farmacologia , Candida albicans/metabolismo , Proteínas Fúngicas/metabolismo , Dinâmica Mitocondrial/efeitos dos fármacos , Proteoma/metabolismo , Proteômica/métodos , Compostos de Anilina/farmacologia , Candida albicans/genética , Candida albicans/fisiologia , Candidíase/microbiologia , Proteínas Fúngicas/genética , Perfilação da Expressão Gênica/métodos , Regulação Fúngica da Expressão Gênica/efeitos dos fármacos , Ontologia Genética , Haploidia , Humanos , Testes de Sensibilidade Microbiana , Dinâmica Mitocondrial/genética , Mutação , Oniocompostos/farmacologia , Proteoma/genéticaRESUMO
BACKGROUND: The antibacterial property of new atraumatic restorative treatment (ART) materials incorporated with Azadirachta indica (Neem) on Streptococcus mutans was carried out. MATERIALS AND METHODS: The study was carried out by using the agar diffusion method to determine the antibacterial property of ART materials (ART-I and ART-II). The zone of inhibition was tabulated, and the data was statistically analyzed using the student t-test. The minimum inhibitory concentrations (MIC) and the minimum bactericidal concentrations (MBC) of the ethanolic extract of Neem were recorded. RESULTS: The MIC and MBC of the mixture of the ethanolic extract of Neem was 3.13% and 12.5% respectively. The zone of inhibition of ART-I and ART-II was 11.81â¯mm and 11.97â¯mm respectively. Significant differences were observed between these two ART materials (Pâ¯=â¯0,08). CONCLUSION: Both the new ART materials i.e. ART-I and ART-II have considerable antibacterial activity against S. mutans.
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Copper oxide nanoparticles (CuO NPs) were synthesized biologically using leaf extract of Camilla japonica. The typical UV-visible spectral peak of CuO NPs was observed at a wavelength of â¼290â¯nm, which confirmed their successful synthesis. From scanning electron microscope (SEM) and transmission electron microscope (TEM) analyses, the synthesized CuO NPs were found to possess spherical shape. Energy dispersive X-ray analyzer (EDX) results revealed that the CuO NPs are almost pure with atomic percentages of 50.92 for Cu and 49.08 for O. Fourier transform infrared (FTIR) confirmed the presence of an absorption peak located at a wavenumber position of â¼480â¯cm-1 typical for highly pure CuO NPs. TEM images displayed that the particles are relatively uniform in size â¼15-25â¯nm. The P. aeruginosa and K. pneumonia showed complete resistance against Hexa 077 antibiotic discs. The result of ≤22 ceftazidime and ≤27 cefotaxime confirmed that both the uropathogens were ESBL producers. The ≥8â¯mm of the MIC stripe further confirmed that both the uropathogens were ESBL producers. Furthermore, the antibacterial activity of CuO NPs against selected ESBL producing P. aeruginosa and K. pneumoniae at minimum inhibition concentration (MIC) of 100⯵g/mL. The decreased cell viability and damaged membrane construction of both the uropathogens were observed by confocal laser scanning microscope (CLSM) using AO/EB stains at desired MIC dose. The morphological damage of the bacterial cells was demonstrated by SEM analysis. Hence, based on the above in vitro findings, the results suggested that the CuO NPs are efficient antibacterial compounds against ESBL producing bacteria, and that the plant leaf mediated CuO NPs can be considered as novel and promising material to act against various infectious bacteria.