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1.
Vet Med Sci ; 10(4): e1498, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38896065

RESUMO

BACKGROUND: Bersama abyssinica Fresen is a plant that is used in folk medicine for the treatment of mastitis and other infectious diseases. OBIECTIVE: The antibacterial activity of methanol crude extract of plant was evaluated against three common bacterial pathogens, including Gram positive (Staphylococcus aureus) and Gram negative (Escherichia coli and Pseudomonas aeruginosa). METHODS: The antibacterial activities and minimum inhibitory concentration of B. abyssinica crude extracts were evaluated using agar-well diffusion and broth dilution methods according to the National Committee for Clinical Laboratory Standards (NCCLS). RESULTS: A significant difference in the antibacterial activity of crude extracts was observed among different levels of concentration against tested isolates. A higher mean inhibition zone diameter was recorded in E. coli (29.2 ± 1.5 mm), followed by S. aureus (27.8 ± 1.1 mm) and P. aeruginosa (18.0 ± 0.7 mm) at a concentration of 100 mg/mL. The antibacterial activity of crude plant extract at 100 mg/mL was comparable with that of a standard antibiotic (27.6 ± 2.6) against S. aureus and E. coli isolates. The findings indicated that bacterial growth inhibition increased as the concentration of the crude extracts increased. E. coli and S. aureus isolates showed significantly higher susceptibilities to crude extracts than P. aeruginosa at all concentrations. The minimum inhibitory concentrations of extracts against S. aureus, E. coli and P. aeruginosa isolates were 0.78 mg/mL, 1.56 mg/mL and 1.56 mg/mL, respectively. CONCLUSIONS: All tested pathogenic bacterial species were susceptible to plant leaf extract and broad-spectrum activity against Gram-positive and Gram-negative bacteria. The study recommends further fractionation of the B. abyssinica plant that contributes to its antibacterial activity and understands the mode of action of this plant against bacteria and other microbes.


Assuntos
Antibacterianos , Bactérias Gram-Negativas , Testes de Sensibilidade Microbiana , Extratos Vegetais , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Antibacterianos/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos
2.
F1000Res ; 13: 36, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38872735

RESUMO

Background: Tigecycline, a glycylcycline antibiotic is a promising option for the treatment of single or multidrug resistant pathogens. The aim of the study was to evaluate the in-vitro Tigecycline susceptibility of various pathogens from clinical samples received at the tertiary care hospitals in South India. Methods: The analysis of specimens from patients admitted were carried out in this prospective cross sectional study. The identification and antimicrobial susceptibility testing was performed by semi-automated Vitek 2 systems and Kirby Bauer method. Pattern of data analysis was done by descriptive statistics. Results: Among 2574 isolates, 812 isolates were Gram positive pathogens and 1762 isolates were Gram negative pathogens. Resistance to Tigecycline was more common among Gram negative pathogens (18.62%) in comparison to the Gram positive pathogens (0.49%). Among 740 Extended Spectrum Beta Lactamases (ESBL) producers such as Klebsiella species & E coli, 629 isolates were susceptible, and 93 isolates were resistant to the tigecycline. All the methicillin resistant Staphylococcus aureus (MRSA) isolates were susceptible to tigecycline. Conclusion: Multidrug resistant (MDR) pathogens like Acinetobacter species, and Klebsiella species were found to be highly effective in vitro to tigecycline for elimination of infections caused by both Gram positive and Gram negative pathogens. The use of combination therapy becomes crucial to prevent the development of Pan Drug resistance.


Assuntos
Farmacorresistência Bacteriana Múltipla , Testes de Sensibilidade Microbiana , Centros de Atenção Terciária , Tigeciclina , Tigeciclina/farmacologia , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Estudos Transversais , Minociclina/análogos & derivados , Minociclina/farmacologia , Minociclina/uso terapêutico , Bactérias Gram-Negativas/efeitos dos fármacos , Estudos Prospectivos , Índia , Bactérias Gram-Positivas/efeitos dos fármacos
3.
Microb Biotechnol ; 17(6): e14483, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38864495

RESUMO

Antimicrobial resistance (AMR) is an escalating global health crisis, driven by the overuse and misuse of antibiotics. Multidrug-resistant Gram-negative bacteria, such as Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae, are particularly concerning due to their high morbidity and mortality rates. In this context, endolysins, derived from bacteriophages, offer a promising alternative to traditional antibiotics. This study introduces LysJEP8, a novel endolysin derived from Escherichia phage JEP8, which exhibits remarkable antimicrobial activity against key Gram-negative members of the ESKAPE group. Comparative assessments highlight LysJEP8's superior performance in reducing bacterial survival rates compared to previously described endolysins, with the most significant impact observed against P. aeruginosa, and notable effects on A. baumannii and K. pneumoniae. The study found that LysJEP8, as predicted by in silico analysis, worked best at lower pH values but lost its effectiveness at salt concentrations close to physiological levels. Importantly, LysJEP8 exhibited remarkable efficacy in the disruption of P. aeruginosa biofilms. This research underscores the potential of LysJEP8 as a valuable candidate for the development of innovative antibacterial agents, particularly against Gram-negative pathogens, and highlights opportunities for further engineering and optimization to address AMR effectively.


Assuntos
Antibacterianos , Farmacorresistência Bacteriana Múltipla , Endopeptidases , Bactérias Gram-Negativas , Endopeptidases/farmacologia , Endopeptidases/metabolismo , Endopeptidases/química , Endopeptidases/genética , Antibacterianos/farmacologia , Antibacterianos/química , Bactérias Gram-Negativas/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Bacteriófagos , Klebsiella pneumoniae/efeitos dos fármacos , Concentração de Íons de Hidrogênio , Acinetobacter baumannii/efeitos dos fármacos , Viabilidade Microbiana/efeitos dos fármacos
4.
BMC Infect Dis ; 24(1): 566, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38844852

RESUMO

BACKGROUND: Early and appropriate antibiotic treatment improves the clinical outcome of patients with sepsis. There is an urgent need for rapid identification (ID) and antimicrobial susceptibility testing (AST) of bacteria that cause bloodstream infection (BSI). Rapid ID and AST can be achieved by short-term incubation on solid medium of positive blood cultures using MALDI-TOF mass spectrometry (MS) and the BD M50 system. The purpose of this study is to evaluate the performance of rapid method compared to traditional method. METHODS: A total of 124 mono-microbial samples were collected. Positive blood culture samples were short-term incubated on blood agar plates and chocolate agar plates for 5 ∼ 7 h, and the rapid ID and AST were achieved through Zybio EXS2000 MS and BD M50 System, respectively. RESULTS: Compared with the traditional 24 h culture for ID, this rapid method can shorten the cultivation time to 5 ∼ 7 h. Accurate organism ID was achieved in 90.6% of Gram-positive bacteria (GP), 98.5% of Gram-negative bacteria (GN), and 100% of fungi. The AST resulted in the 98.5% essential agreement (EA) and 97.1% category agreements (CA) in NMIC-413, 99.4% EA and 98.9% CA in PMIC-92, 100% both EA and CA in SMIC-2. Besides, this method can be used for 67.2% (264/393) of culture bottles during routine work. The mean turn-around time (TAT) for obtaining final results by conventional method is approximately 72.6 ± 10.5 h, which is nearly 24 h longer than the rapid method. CONCLUSIONS: The newly described method is expected to provide faster and reliable ID and AST results, making it an important tool for rapid management of blood cultures (BCs). In addition, this rapid method can be used to process most positive blood cultures, enabling patients to receive rapid and effective treatment.


Assuntos
Bactérias , Testes de Sensibilidade Microbiana , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Humanos , Testes de Sensibilidade Microbiana/métodos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Bactérias/efeitos dos fármacos , Bactérias/isolamento & purificação , Antibacterianos/farmacologia , Fungos/efeitos dos fármacos , Fungos/isolamento & purificação , Hemocultura/métodos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/isolamento & purificação , Fatores de Tempo , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Positivas/isolamento & purificação , Sepse/microbiologia , Sepse/tratamento farmacológico , Sepse/diagnóstico
5.
Sci Rep ; 14(1): 12719, 2024 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-38830875

RESUMO

Polypeptide-targeted MALDI-TOF MS for microbial species identification has revolutionized microbiology. However, no practical MALDI-TOF MS identification method for O-antigen polysaccharides, a major indicator for epidemiological classification within a species of gram-negative bacteria, is available. We describe a simple MALDI glycotyping method for O-antigens that simultaneously identifies the molecular mass of the repeating units and the monosaccharide composition of the O-antigen. We analyzed the Escherichia coli O1, O6, and O157-type strains. Conventional species identification based on polypeptide patterns and O-antigen polysaccharide typing can be performed in parallel from a single colony using our MALDI-TOF MS workflow. Moreover, subtyping within the same O-antigen and parallel colony-specific O-antigen determination from mixed strains, including the simultaneous identification of multiple strains-derived O-antigens within selected colony, were performed. In MALDI glycotyping of two Enterobacteriaceae strains, a Citrobacter freundii strain serologically cross-reactive with E. coli O157 gave a MALDI spectral pattern identical to E. coli O157. On the other hand, an Edwardsiella tarda strain with no reported O-antigen cross-reactivity gave a MALDI spectral pattern of unknown O-antigen repeating units. The method described in this study allows the parallel and rapid identification of microbial genera, species, and serotypes of surface polysaccharides using a single MALDI-TOF MS instrument.


Assuntos
Antígenos O , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Antígenos O/química , Antígenos O/imunologia , Antígenos O/análise , Bactérias Gram-Negativas/imunologia , Bactérias Gram-Negativas/classificação , Escherichia coli
6.
J Coll Physicians Surg Pak ; 34(6): 677-681, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38840350

RESUMO

OBJECTIVE: To compare the susceptibility of colistin by two methods in extensive drug-resistant (XDR) Gram-negative isolates from ICU patients. STUDY DESIGN: Cross-sectional comparative analysis. Place and Duration of the Study: Department of Microbiology, Combined Military Hospital Karachi, Pakistan, from August 2022 to February 2023. METHODOLOGY: A total of 100 clinical specimens received from the intensive care unit yielded growth of extensively drug-resistant gram-negative bacteria, which were evaluated for polymyxin E susceptibility. The agar dilution method was compared with the reference broth microdilution (BMD) method. Minimum inhibitory concentration (MIC) was noted for both methods. RESULTS: Comparison of the MIC method by agar dilution showed a 90% correlation with the reference method of broth microdilution. With MICs within the acceptable range of the clinical and laboratory standards institute (CLSI) recommendations, 89 isolates were susceptible to colistin, whereas only 11 remained resistant. Polymyxin E's MIC 50 and MIC 90 were determined to be 1 and 2 µg/ml, respectively, with 97% susceptibility. CONCLUSION: Agar dilution susceptibility method can be used for screening purposes for the susceptibility testing of polymyxin E. This method is reliable and can easily identify the heteroresistance. KEY WORDS: Extensively drug-resistant, Broth microdilution, Multidrug-resistant, Agar dilution, Minimum inhibitory concentration, Colony forming unit.


Assuntos
Antibacterianos , Colistina , Farmacorresistência Bacteriana Múltipla , Bactérias Gram-Negativas , Infecções por Bactérias Gram-Negativas , Unidades de Terapia Intensiva , Testes de Sensibilidade Microbiana , Colistina/farmacologia , Humanos , Testes de Sensibilidade Microbiana/métodos , Antibacterianos/farmacologia , Estudos Transversais , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/isolamento & purificação , Paquistão , Infecções por Bactérias Gram-Negativas/microbiologia , Infecções por Bactérias Gram-Negativas/tratamento farmacológico
7.
Carbohydr Polym ; 341: 122321, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38876723

RESUMO

Starch-based biofilms are biodegradable, but their application is limited by lower mechanical strength and absence of antimicrobial properties. In this context, the present study attempted to unleash the potential of nanotechnology for synthesizing nano-starch (NS) and tannic acid-coated nano-starch (T-NS) for augmenting the tensile strength and antimicrobial properties of starch-based biofilms. Moreover, this study reports one of the first such attempts to improve the commercial viability of starch extracted from the corms of Amorphophallus paeoniifolius. In this study, NS and T-NS samples were first synthesized by the physical and chemical modification of the native starch (S) molecules. The NS and T-NS samples showed significantly smaller granule size, lower moisture content, and swelling power. Further, amendments with NS and T-NS samples (25 % and 50 %) to the native starch molecules were performed to obtain biofilm samples. The NSB (NS amended) and T-NSB (T-NS amended) biofilms showed comparatively higher tensile strength than SB films (100 % starch-based). The T-NSB showed greater antimicrobial activity against gram-positive and gram-negative bacteria. All the biofilms showed almost complete biodegradation in soil (in 10 days). Therefore, it can be concluded that additives like NS and T-NS can improve starch-based biofilms' mechanical strength and antimicrobial properties with considerable biodegradability.


Assuntos
Antibacterianos , Biofilmes , Amido , Taninos , Resistência à Tração , Amido/química , Taninos/química , Taninos/farmacologia , Biofilmes/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/química , Testes de Sensibilidade Microbiana , Nanopartículas/química , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Polifenóis
8.
Yakugaku Zasshi ; 144(6): 627-631, 2024.
Artigo em Japonês | MEDLINE | ID: mdl-38825471

RESUMO

Cefiderocol is a novel siderophore-conjugated cephalosporin with a catechol residue acting as an iron chelator. Cefiderocol forms a chelating complex with ferric iron and is transported rapidly into bacterial cells through iron-uptake systems. As a result, cefiderocol shows good activity against Gram-negative bacteria, including carbapenem-resistant isolates that are causing significant global health issues. Cefiderocol has been approved for clinical use in the United States and Europe, where it is being used to treat infection caused by carbapenem-resistant Gram-negative pathogens.


Assuntos
Antibacterianos , Cefiderocol , Cefalosporinas , Bactérias Gram-Negativas , Sideróforos , Cefalosporinas/farmacologia , Cefalosporinas/química , Sideróforos/química , Humanos , Antibacterianos/farmacologia , Antibacterianos/química , Bactérias Gram-Negativas/efeitos dos fármacos , Quelantes de Ferro/farmacologia , Ferro/metabolismo , Farmacorresistência Bacteriana , Descoberta de Drogas , Carbapenêmicos/farmacologia , Infecções por Bactérias Gram-Negativas/tratamento farmacológico
9.
Biomed Pharmacother ; 176: 116810, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38823276

RESUMO

Globally, infections due to multi-drug resistant (MDR) Gram-negative bacterial (GNB) pathogens are on the rise, negatively impacting morbidity and mortality, necessitating urgent treatment alternatives. Herein, we report a detailed bio-evaluation of an ultrashort, cationic lipopeptide 'SVAP9I' that demonstrated potent antibiotic activity and acted as an adjuvant to potentiate existing antibiotic classes towards GNBs. Newly synthesized lipopeptides were screened against ESKAPE pathogens and cytotoxicity assays were performed to evaluate the selectivity index (SI). SVAP9I exhibited broad-spectrum antibacterial activity against critical MDR-GNB pathogens including members of Enterobacteriaceae (MIC 4-8 mg/L), with a favorable CC50 value of ≥100 mg/L and no detectable resistance even after 50th serial passage. It demonstrated fast concentration-dependent bactericidal action as determined via time-kill analysis and also retained full potency against polymyxin B-resistant E. coli, indicating distinct mode of action. SVAP9I targeted E. coli's outer and inner membranes by binding to LPS and phospholipids such as cardiolipin and phosphatidylglycerol. Membrane damage resulted in ROS generation, depleted intracellular ATP concentration and a concomitant increase in extracellular ATP. Checkerboard assays showed SVAP9I's synergism with narrow-spectrum antibiotics like vancomycin, fusidic acid and rifampicin, potentiating their efficacy against MDR-GNB pathogens, including carbapenem-resistant Acinetobacter baumannii (CRAB), a WHO critical priority pathogen. In a murine neutropenic thigh infection model, SVAP9I and rifampicin synergized to express excellent antibacterial efficacy against MDR-CRAB outcompeting polymyxin B. Taken together, SVAP9I's distinct membrane-targeting broad-spectrum action, lack of resistance and strong in vitro andin vivopotency in synergism with narrow spectrum antibiotics like rifampicin suggests its potential as a novel antibiotic adjuvant for the treatment of serious MDR-GNB infections.


Assuntos
Antibacterianos , Farmacorresistência Bacteriana Múltipla , Bactérias Gram-Negativas , Lipopeptídeos , Testes de Sensibilidade Microbiana , Animais , Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Camundongos , Lipopeptídeos/farmacologia , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/microbiologia , Sinergismo Farmacológico , Feminino , Humanos , Adjuvantes Farmacêuticos/farmacologia
10.
J Assoc Physicians India ; 72(6): 69-73, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38881138

RESUMO

OBJECTIVES: Antimicrobial resistance (AMR) is a major health issue. To determine trends in bacterial organisms in respiratory tract infections (RTIs) and their antibiotic sensitivity at a tertiary care center in India, we performed this study. METHODS: Successive samples received from January 2017 to December 2021 from the respiratory tract (sputum, endotracheal secretion, and bronchoalveolar lavage) from intensive care units and medical inpatients were processed for bacterial growth. The identification of isolates and antibiotic sensitivity patterns was performed using an automated VITEK-2 system. Descriptive statistics are reported. RESULTS: We received 7,204 respiratory samples. Significant bacterial growth was in 3,000 (41.6%), and 2,992 (41.5%) were gram-negative. Klebsiella pneumoniae was the most prevalent, followed by Pseudomonas aeruginosa, Acinetobacter baumannii, Escherichia coli, and Enterobacter aerogenes. Increasing secular trends were observed for Klebsiella and Pseudomonas and declining trends for Acinetobacter and Escherichia (p < 0.05). Antimicrobial sensitivity patterns showed that Klebsiella, Pseudomonas, Acinetobacter, E. coli, and Enterobacter had a high sensitivity with colistin and polymyxin (99-100%). Moderate sensitivity was observed with carbapenems (Acinetobacter: 47.5%, Enterobacter: 62.0%, Escherichia: 76.5%, Klebsiella: 72.3%, Pseudomonas: 66.7%) and tigecycline (Acinetobacter: 50.4%, Enterobacter: 68.0%, Escherichia: 81.1%, Klebsiella: 66.6%, Pseudomonas: 0%). Aminoglycosides had <50% sensitivity for various organisms, and <25% sensitivity was observed with third-generation cephalosporins and quinolones. Trend analysis showed persistent sensitivity of various pathogenic bacteria to colistin and polymyxin and declining pharmacological sensitivity in Acinetobacter (carbapenems and tigecycline), Escherichia (carbapenems, quinolones, and tigecycline), Klebsiella (carbapenems, quinolones, aminoglycosides, and tigecycline), and Pseudomonas (carbapenems and aminoglycosides) species (p < 0.05). CONCLUSION: Common respiratory tract gram-negative bacterial pathogens at a tertiary care hospital are K. pneumoniae, P. aeruginosa, A. baumannii, and E. coli. All these bacteria demonstrate high sensitivity only with colistin and polymyxin. Significant AMR is observed to carbapenems, tigecycline, aminoglycosides, and third-generation cephalosporins. Secular trends show declining antimicrobial sensitivity among various bacterial pathogens.


Assuntos
Antibacterianos , Testes de Sensibilidade Microbiana , Infecções Respiratórias , Centros de Atenção Terciária , Humanos , Infecções Respiratórias/microbiologia , Infecções Respiratórias/tratamento farmacológico , Antibacterianos/farmacologia , Índia/epidemiologia , Farmacorresistência Bacteriana , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/isolamento & purificação
11.
Anal Chem ; 96(23): 9317-9324, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38818541

RESUMO

Inaccurate or cumbersome clinical pathogen diagnosis between Gram-positive bacteria (G+) and Gram-negative (G-) bacteria lead to delayed clinical therapeutic interventions. Microelectrode-based electrochemical sensors exhibit the significant advantages of rapid response and minimal sample consumption, but the loading capacity and discrimination precision are weak. Herein, we develop reversible fusion-fission MXene-based fiber microelectrodes for G+/G- bacteria analysis. During the fissuring process, the spatial utilization, loading capacity, sensitivity, and selectivity of microelectrodes were maximized, and polymyxin B and vancomycin were assembled for G+/G- identification. The surface-tension-driven reversible fusion facilitated its reusability. A deep learning model was further applied for the electrochemical impedance spectroscopy (EIS) identification in diverse ratio concentrations of G+ and G- of (1:100-100:1) with higher accuracy (>93%) and gave predictable detection results for unknown samples. Meanwhile, the as-proposed sensing platform reached higher sensitivity toward E. coli (24.3 CFU/mL) and S. aureus (37.2 CFU/mL) in 20 min. The as-proposed platform provides valuable insights for bacterium discrimination and quantification.


Assuntos
Microeletrodos , Bactérias Gram-Positivas/isolamento & purificação , Bactérias Gram-Negativas/isolamento & purificação , Escherichia coli/isolamento & purificação , Staphylococcus aureus/isolamento & purificação , Técnicas Eletroquímicas/instrumentação , Vancomicina/farmacologia , Antibacterianos/farmacologia , Antibacterianos/análise , Polimixina B/química , Polimixina B/farmacologia , Espectroscopia Dielétrica
12.
Mol Biol Evol ; 41(5)2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38768245

RESUMO

As species diverge, a wide range of evolutionary processes lead to changes in protein-protein interaction (PPI) networks and metabolic networks. The rate at which molecular networks evolve is an important question in evolutionary biology. Previous empirical work has focused on interactomes from model organisms to calculate rewiring rates, but this is limited by the relatively small number of species and sparse nature of network data across species. We present a proxy for variation in network topology: variation in drug-drug interactions (DDIs), obtained by studying drug combinations (DCs) across taxa. Here, we propose the rate at which DDIs change across species as an estimate of the rate at which the underlying molecular network changes as species diverge. We computed the evolutionary rates of DDIs using previously published data from a high-throughput study in gram-negative bacteria. Using phylogenetic comparative methods, we found that DDIs diverge rapidly over short evolutionary time periods, but that divergence saturates over longer time periods. In parallel, we mapped drugs with known targets in PPI and cofunctional networks. We found that the targets of synergistic DDIs are closer in these networks than other types of DCs and that synergistic interactions have a higher evolutionary rate, meaning that nodes that are closer evolve at a faster rate. Future studies of network evolution may use DC data to gain larger-scale perspectives on the details of network evolution within and between species.


Assuntos
Filogenia , Evolução Molecular , Mapas de Interação de Proteínas , Interações Medicamentosas , Bactérias Gram-Negativas/genética , Evolução Biológica , Redes e Vias Metabólicas
13.
J Clin Lab Anal ; 38(9): e25043, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38804639

RESUMO

BACKGROUND: Rapid antimicrobial susceptibility testing (AST) for bloodstream infections (BSIs) facilitates the optimization of antimicrobial therapy, preventing antimicrobial resistance and improving patient outcomes. QMAC-dRAST (QuantaMatrix Inc., Korea) is a rapid AST platform based on microfluidic chip technology that performs AST directly using positive blood culture broth (PBCB). This study evaluated the performance of QMAC-dRAST for Gram-negative bacteria using PBCB and subcultured colony isolates, comparing it with that of VITEK 2 (bioMérieux, France) using broth microdilution (BMD) as the reference method. METHODS: We included 141 Gram-negative blood culture isolates from patients with BSI and 12 carbapenemase-producing clinical isolates of Enterobacterales spiked into blood culture bottles. QMAC-dRAST performance was evaluated using PBCB and colony isolates, whereas VITEK 2 and BMD were tested only on colony isolates. RESULTS: For PBCB, QMAC-dRAST achieved 92.1% categorical agreement (CA), 95.3% essential agreement (EA), with 1.8% very major errors (VMEs), 3.5% major errors (MEs), and 5.2% minor errors (mEs). With colony isolates, it exhibited 92.5% CA and 95.1% EA, with 2.0% VMEs, 3.2% MEs, and 4.8% mEs. VITEK 2 showed 94.1% CA and 96.0% EA, with 4.3% VMEs, 0.4% MEs, and 4.3% mEs. QMAC-dRAST yielded elevated error rates for specific antimicrobial agents, with high VMEs for carbapenems and aminoglycosides. The median time to result for QMAC-dRAST was 5.9 h for PBCB samples and 6.1 h for subcultured colony isolates. CONCLUSIONS: The QMAC-dRAST system demonstrated considerable strengths and comparable performance to the VITEK 2 system; however, challenges were discerned with specific antimicrobial agents, underlining a necessity for improvement.


Assuntos
Antibacterianos , Hemocultura , Bactérias Gram-Negativas , Testes de Sensibilidade Microbiana , Testes de Sensibilidade Microbiana/métodos , Humanos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/isolamento & purificação , Hemocultura/métodos , Antibacterianos/farmacologia
14.
Biochim Biophys Acta Biomembr ; 1866(6): 184336, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38763273

RESUMO

Short systemic half- life of Antimicrobial Peptides (AMP) is one of the major bottlenecks that limits their successful commercialization as therapeutics. In this work, we have designed analogs of the natural AMP Jelleine, obtained from royal jelly of apis mellifera. Among the designed peptides, J3 and J4 were the most potent with broad spectrum activities against a varied class of ESKAPE pathogens and fungus C. albicans. All the developed peptides were more effective against Gram-negative bacteria in comparison to the Gram-positive pathogens, and were especially effective against P. aeruginosa and C. albicans.J3 and J4 were completely trypsin resistant and serum stable, while retaining the non-cytotoxicity of the parent Jelleine, Jc. The designed peptides were membranolytic in their mode of action. CD and MD simulations in the presence of bilayers, established that J3 and J4 were non-structured even upon membrane binding and suggested that biological properties of the AMPs were innocent of any specific secondary structural requirements. Enhancement of charge to increase the antimicrobial potency, controlling the hydrophobic-hydrophilic balance to maintain non-cytotoxicity and induction of unnatural amino acid residues to impart protease resistance, remains some of the fundamental principles in the design of more effective antimicrobial therapeutics of the future, which may help combat the quickly rising menace of antimicrobial resistance in the microbes.


Assuntos
Peptídeos Catiônicos Antimicrobianos , Candida albicans , Testes de Sensibilidade Microbiana , Peptídeos Catiônicos Antimicrobianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/síntese química , Candida albicans/efeitos dos fármacos , Animais , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Bactérias Gram-Negativas/efeitos dos fármacos , Peptídeo Hidrolases/química , Peptídeo Hidrolases/metabolismo , Humanos , Abelhas , Peptídeos Antimicrobianos/farmacologia , Peptídeos Antimicrobianos/química , Simulação de Dinâmica Molecular , Oligopeptídeos
15.
PLoS One ; 19(5): e0301767, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38758936

RESUMO

The primary objective of this study was to isolate bacteria from diabetic foot ulcers and subsequently assess their antibiotic resistance capabilities. Seventy-five patients diagnosed with diabetic foot ulcers were investigated. A number of these patients (97.33%) had type 2 diabetes, with a significant proportion of them having been diagnosed for 1-5 years (29.33%). Notably, a substantial number of these individuals were on insulin usage (78.66%). Among the patients under examination, 49.33% reported having no use of tobacco products, alcohol, or betel leaf. The ulcers analyzed in this study were classified into grades 1-5 according to the Wagner scale. Wagner grade 2 diabetic foot ulcers had the highest number of culture-positive patients, at 33.33%. Pus samples collected from patients were cultured on selective media, and bacterial identity was confirmed by biochemical tests and polymerase chain reaction. A total of 141 isolates were isolated. Among the isolates, 82.97% gram-negative bacteria and 17.02% gram-positive bacteria were detected. Klebsiella pneumoniae was the most common isolate. Proteus spp., Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus were also detected. Approximately 61.33% of the ulcers exhibited were polybacterial. In this study, it was observed that all bacterial isolates, except for Proteus spp., were primarily detected in patients classified under Wagner's grade 2. Moreover, antibiotic susceptibility was also tested on these 141 isolates. Among them, Escherichia coli showed the highest multidrug resistance, 81.81%. Most of the gram-negative bacteria were resistant to ampicillin. All of the gram-negative isolates exhibited high levels of susceptibility to piperacillin-tazobactam, and these levels were Klebsiella pneumoniae (97.56%), Pseudomonas aeruginosa (95.24%), Escherichia coli (81.82%), and Proteus spp. (80%). On the other hand, gram-positive Staphylococcus aureus mostly showed sensitivity towards vancomycin and norfloxacin (79.17%).


Assuntos
Antibacterianos , Pé Diabético , Testes de Sensibilidade Microbiana , Humanos , Pé Diabético/microbiologia , Pé Diabético/tratamento farmacológico , Masculino , Feminino , Pessoa de Meia-Idade , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Bangladesh/epidemiologia , Idoso , Adulto , Farmacorresistência Bacteriana , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/isolamento & purificação , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Positivas/isolamento & purificação , Escherichia coli/efeitos dos fármacos , Escherichia coli/isolamento & purificação , Diabetes Mellitus Tipo 2/microbiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/isolamento & purificação
16.
Carbohydr Polym ; 338: 122218, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38763705

RESUMO

Here, biogenic and multifunctional active food coatings and packaging with UV shielding and antimicrobial properties were structured from the aqueous dispersion of an industrial byproduct, suberin, which was stabilized with amphiphilic cellulose nanofibers (CNF). The dual-functioning CNF, synthesized in a deep eutectic solvent, functioned as an efficient suberin dispersant and reinforcing agent in the packaging design. The nanofibrillar percolation network of CNF provided a steric hindrance against the coalescence of the suberin particles. The low CNF dosage of 0.5 wt% resulted in dispersion with optimal viscosity (208.70 Pa.s), enhanced stability (instability index of <0.001), and reduced particle size (9.37 ± 2.43 µm). The dispersion of suberin and CNF was further converted into self-standing films with superior UV-blocking capability, good thermal stability, improved hydrophobicity (increase in water contact angle from 61° ± 0.15 to 83° ± 5.11), and antimicrobial properties against gram-negative bacteria. Finally, the synergistic bicomponent dispersions were demonstrated as fruit coatings for bananas and packaging for strawberries to promote their self-life. The coatings and packaging considerably mitigated fruit deterioration and improved their freshness by preventing moisture loss and microbial attack. This sustainable approach is expected to pave the way toward advanced, biogenic, and active food packaging based on widely available bioresources.


Assuntos
Celulose , Embalagem de Alimentos , Lipídeos , Nanofibras , Madeira , Nanofibras/química , Celulose/química , Embalagem de Alimentos/métodos , Madeira/química , Lipídeos/química , Interações Hidrofóbicas e Hidrofílicas , Antibacterianos/química , Antibacterianos/farmacologia , Viscosidade , Musa/química , Água/química , Bactérias Gram-Negativas/efeitos dos fármacos , Frutas/química
17.
BMC Infect Dis ; 24(1): 501, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38760687

RESUMO

BACKGROUND: The study aims were to evaluate the species distribution and antimicrobial resistance profile of Gram-negative pathogens isolated from specimens of intra-abdominal infections (IAI), urinary tract infections (UTI), respiratory tract infections (RTI), and blood stream infections (BSI) in emergency departments (EDs) in China. METHODS: From 2016 to 2019, 656 isolates were collected from 18 hospitals across China. Minimum inhibitory concentrations were determined by CLSI broth microdilution and interpreted according to CLSI M100 (2021) guidelines. In addition, organ-specific weighted incidence antibiograms (OSWIAs) were constructed. RESULTS: Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) were the most common pathogens isolated from BSI, IAI and UTI, accounting for 80% of the Gram-negative clinical isolates, while Pseudomonas aeruginosa (P. aeruginosa) was mainly isolated from RTI. E. coli showed < 10% resistance rates to amikacin, colistin, ertapenem, imipenem, meropenem and piperacillin/tazobactam. K. pneumoniae exhibited low resistance rates only to colistin (6.4%) and amikacin (17.5%) with resistance rates of 25-29% to carbapenems. P. aeruginosa exhibited low resistance rates only to amikacin (13.4%), colistin (11.6%), and tobramycin (10.8%) with over 30% resistance to all traditional antipseudomonal antimicrobials including ceftazidime, cefepime, carbapenems and levofloxacin. OSWIAs were different at different infection sites. Among them, the susceptibility of RTI to conventional antibiotics was lower than for IAI, UTI or BSI. CONCLUSIONS: Gram-negative bacteria collected from Chinese EDs exhibited high resistance to commonly used antibiotics. Susceptibilities were organ specific for different infection sites, knowledge which will be useful for guiding empirical therapies in the clinic.


Assuntos
Antibacterianos , Serviço Hospitalar de Emergência , Bactérias Gram-Negativas , Infecções por Bactérias Gram-Negativas , Testes de Sensibilidade Microbiana , Humanos , China/epidemiologia , Antibacterianos/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/isolamento & purificação , Serviço Hospitalar de Emergência/estatística & dados numéricos , Infecções por Bactérias Gram-Negativas/microbiologia , Infecções por Bactérias Gram-Negativas/epidemiologia , Infecções Urinárias/microbiologia , Infecções Urinárias/epidemiologia , Infecções Respiratórias/microbiologia , Infecções Respiratórias/epidemiologia , Infecções Intra-Abdominais/microbiologia , Infecções Intra-Abdominais/epidemiologia , Farmacorresistência Bacteriana , Feminino , Masculino
18.
Nat Commun ; 15(1): 3947, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38729951

RESUMO

Gram-negative bacteria (GNB) are a major cause of neonatal sepsis in low- and middle-income countries (LMICs). Although the World Health Organization (WHO) reports that over 80% of these sepsis deaths could be prevented through improved treatment, the efficacy of the currently recommended first- and second-line treatment regimens for this condition is increasingly affected by high rates of drug resistance. Here we assess three well known antibiotics, fosfomycin, flomoxef and amikacin, in combination as potential antibiotic treatment regimens by investigating the drug resistance and genetic profiles of commonly isolated GNB causing neonatal sepsis in LMICs. The five most prevalent bacterial isolates in the NeoOBS study (NCT03721302) are Klebsiella pneumoniae, Acinetobacter baumannii, E. coli, Serratia marcescens and Enterobacter cloacae complex. Among these isolates, high levels of ESBL and carbapenemase encoding genes are detected along with resistance to ampicillin, gentamicin and cefotaxime, the current WHO recommended empiric regimens. The three new combinations show excellent in vitro activity against ESBL-producing K. pneumoniae and E. coli isolates. Our data should further inform and support the clinical evaluation of these three antibiotic combinations for the treatment of neonatal sepsis in areas with high rates of multidrug-resistant Gram-negative bacteria.


Assuntos
Acinetobacter baumannii , Antibacterianos , Bactérias Gram-Negativas , Infecções por Bactérias Gram-Negativas , Klebsiella pneumoniae , Testes de Sensibilidade Microbiana , Sepse Neonatal , Humanos , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Sepse Neonatal/microbiologia , Sepse Neonatal/tratamento farmacológico , Recém-Nascido , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/genética , Bactérias Gram-Negativas/isolamento & purificação , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/microbiologia , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/isolamento & purificação , Acinetobacter baumannii/genética , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/isolamento & purificação , Klebsiella pneumoniae/genética , Amicacina/farmacologia , Amicacina/uso terapêutico , Fosfomicina/farmacologia , Fosfomicina/uso terapêutico , beta-Lactamases/genética , beta-Lactamases/metabolismo , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Escherichia coli/isolamento & purificação , Países em Desenvolvimento , Farmacorresistência Bacteriana Múltipla/genética , Quimioterapia Combinada , Serratia marcescens/efeitos dos fármacos , Serratia marcescens/genética , Serratia marcescens/isolamento & purificação , Enterobacter cloacae/efeitos dos fármacos , Enterobacter cloacae/genética , Enterobacter cloacae/isolamento & purificação , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo
19.
J Microbiol ; 62(4): 261-275, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38816673

RESUMO

Lipopolysaccharide (LPS) is a critical component of the extracellular leaflet within the bacterial outer membrane, forming an effective physical barrier against environmental threats in Gram-negative bacteria. After LPS is synthesized and matured in the bacterial cytoplasm and the inner membrane (IM), LPS is inserted into the outer membrane (OM) through the ATP-driven LPS transport (Lpt) pathway, which is an energy-intensive process. A trans-envelope complex that contains seven Lpt proteins (LptA-LptG) is crucial for extracting LPS from the IM and transporting it across the periplasm to the OM. The last step in LPS transport involves the mediation of the LptDE complex, facilitating the insertion of LPS into the outer leaflet of the OM. As the Lpt system plays an essential role in maintaining the impermeability of the OM via LPS decoration, the interactions between these interconnected subunits, which are meticulously regulated, may be potential targets for the development of new antibiotics to combat multidrug-resistant Gram-negative bacteria. In this review, we aimed to provide an overview of current research concerning the structural interactions within the Lpt system and their implications to clarify the function and regulation of LPS transport in the overall process of OM biogenesis. Additionally, we explored studies on the development of therapeutic inhibitors of LPS transport, the factors that limit success, and future prospects.


Assuntos
Antibacterianos , Bactérias Gram-Negativas , Lipopolissacarídeos , Lipopolissacarídeos/metabolismo , Antibacterianos/farmacologia , Antibacterianos/metabolismo , Antibacterianos/química , Bactérias Gram-Negativas/metabolismo , Bactérias Gram-Negativas/efeitos dos fármacos , Transporte Biológico , Proteínas da Membrana Bacteriana Externa/metabolismo , Proteínas da Membrana Bacteriana Externa/química , Proteínas de Membrana Transportadoras/metabolismo , Proteínas de Membrana Transportadoras/química , Membrana Externa Bacteriana/metabolismo , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Farmacorresistência Bacteriana Múltipla
20.
Inorg Chem ; 63(23): 10691-10704, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38805682

RESUMO

As the main challenge of dental healthcare, oral infectious diseases are highly associated with the colonization of pathogenic microbes. However, current antibacterial treatments in the field of stomatology still lack a facile, safe, and universal approach. Herein, we report the controllable synthesis of copper aluminum-layered double hydroxides (CuAl-LDHs) with high Fenton-like catalytic activity, which can be utilized in the treatment of oral infectious diseases with negligible side effects. Our strategy can efficiently avoid the unwanted doping of other divalent metal ions in the synthesis of Cu-contained LDHs and result in the formation of binary CuAl-LDHs with high crystallinity and purity. Evidenced by experimental and theoretical results, CuAl-LDHs exhibit excellent catalytic ability toward the ·OH generation in the presence of H2O2 and hold strong affinity toward bacteria, endowing them with great catalytic sterilization against both Gram-positive and Gram-negative bacteria. As expected, these CuAl-LDHs provide outstanding treatments for mucosal infection and periodontitis by promoting wound healing and remodeling of the periodontal microenvironment. Moreover, toxicity investigation demonstrates the overall safety. Accordingly, the current study not only provides a convenient and economic strategy for treating oral infectious diseases but also extends the development of novel LDH-based Fenton or Fenton-like antibacterial reagents for further biomedical applications.


Assuntos
Alumínio , Antibacterianos , Cobre , Peróxido de Hidrogênio , Cobre/química , Cobre/farmacologia , Catálise , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Peróxido de Hidrogênio/química , Peróxido de Hidrogênio/farmacologia , Alumínio/química , Alumínio/farmacologia , Hidróxidos/química , Hidróxidos/farmacologia , Testes de Sensibilidade Microbiana , Animais , Ferro/química , Ferro/farmacologia , Saúde Bucal , Camundongos , Humanos , Bactérias Gram-Negativas/efeitos dos fármacos
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