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1.
Braz. j. oral sci ; 20: e213690, jan.-dez. 2021. ilus
Artigo em Inglês | LILACS, BBO - Odontologia | ID: biblio-1281104

RESUMO

Aim: to develop a model for regenerative endodontics using newly-weaned Wistar rats immature molars with pulp necrosis to histologically describe the evolution of apical tissues following treatment with a bi-antibiotic paste, induced bloodclot formation and MTA. Methods: Ten 25-day-old female Wistar rats were divided into an initial control group (Ci) and two experimental groups in which pulp necrosis was experimentally induced on the left mandibular first molar by exposing the pulp chamber and leaving it open to the oral environment. One of the experimental groups was left untreated (E1) while the other was submitted to a protocol of regenerative endodontics 10 days thereafter (E2). Fifteen days after placement of a bi-antibiotic paste, bleeding was induced into the root canal space and MTA was placed upon. Animals were euthanized 30 days later. Right mandibular first molars served as an 80-day-old final control group (Cf). Each hemimandible was histologically processed to analyse parameters associated with root development. Statistical analysis was carried by means of ANOVA; p values below 0.05 were considered statistically significant. Results: baseline (i.e. 25-days old) mean root length and apical diameter of the distal root canal were 1.84±0.25 and 0.38±0.02mm respectively. Following the regenerative endodontic protocol, cells lining the walls of the root canal and significant increase to both length (2.37±0.22mm) and diameter (0.32±0.03 mm) were observed. Conclusions: newly-weaned Wistar rats serve as a suitable model to evaluate regenerative endodontic protocols. However, further research is needed in order to disclose the nature of the cells and/or cell mediators involved


Assuntos
Animais , Ratos , Tratamento do Canal Radicular , Necrose da Polpa Dentária , Endodontia Regenerativa , Antibacterianos
2.
J Oral Sci ; 63(3): 217-226, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34193777

RESUMO

A systematic review was carried out to identify if periprocedural administration of systemic antibiotics could decrease risk of medication-related osteonecrosis of the jaws (MRONJ) in patients under antiresorptive and/or biologic agents for teeth extraction. PubMed/MEDLINE and Scopus were systematically searched for case-series with more than 10 patients, retrospective/prospective studies, and trials concerning this issue. Manual searching of references from previous reviews was also carried out. Of 1,512 results, 17 studies were included, focusing on antibiotics for extraction in patients under intravenous bisphosphonates (8 studies), oral bisphosphonates (2 studies), oral and intravenous bisphosphonates (6 studies), and denosumab (1 study), of which 12 performed dental extraction with surgical flap. With no trials found, "quality in prognosis studies" (QUIPS) tool was used to evaluate risk of bias. First-line treatment was 2-3 grams of oral amoxicillin in 76.4% of studies; 300-600 mg of clindamycin was the alternative treatment in 23.5% of studies. Treatment ranged from 3 to 20 days, consisting of 6-7 days in 47% of studies. No microbiologic insight was provided. A significantly higher risk of MRONJ for patients unexposed to antibiotics was provided in one retrospective study. QUIPS tool revealed moderate-high risk of bias. With empirical data from bias-carrying, heterogeneous observational studies, the validity of antibiotics is yet to be established.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos , Conservadores da Densidade Óssea , Antibacterianos/efeitos adversos , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/tratamento farmacológico , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/prevenção & controle , Humanos , Estudos Prospectivos , Estudos Retrospectivos , Extração Dentária
3.
Talanta ; 233: 122535, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34215038

RESUMO

Bacterial infection poses a serious threat to human health worldwide. Rapid antimicrobial susceptibility testing (AST) is essential for the clinical treatment of bacterial infection patients. However, the traditional AST relies on bacteria culture, which is time-consuming and limits the analysis to culturable species. Herein, we present a laser desorption ionization (LDI) mass spectrometry-based method for rapid bacterial viability assessment and AST by tracing the redox of resazurin (RS) by viable bacteria. RS as well as its reduction product, fluorescent resorufin (RF), can be directly detected by LDI-MS in the absence of matrix. The intensity ratio between RF and RS can be used to assess the viability of bacteria in specimens. We have demonstrated the high efficiency of the method using different bacterial species, including K. pneumoniae, S. aureus, E. coli, and P. aeruginosa, and various antibiotic drugs, such as ciprofloxacin, ampicillin, tetracycline, oxytetracycline, ciprofloxacin and levofloxacin. Compared to traditional methods based on optical absorption, the current method is faster and more sensitive. Furthermore, we applied the method to bacterial viability detection and AST using human body fluid samples, i.e. serum and urine, demonstrating that it can screen rapidly appropriate antibiotic drugs for timely clinical treatment of infectious diseases. With the advantages of simplicity in methodology as well as sensitivity and speed in analysis, the current method holds the potential of clinical usages.


Assuntos
Escherichia coli , Staphylococcus aureus , Antibacterianos/farmacologia , Humanos , Lasers , Testes de Sensibilidade Microbiana , Viabilidade Microbiana , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
4.
Talanta ; 233: 122536, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34215039

RESUMO

Preparation of porphyrin-based covalent organic frameworks (Por-COFs) with high photosensitizing activity for photodynamic inactivation of bacteria is of great challenge, but significant for economy and human health. Herein, we show a conjugation-regulating strategy to design and synthesize Por-COFs with high photosensitizing activity for the photodynamic inactivation of bacteria. Terephthalaldehyde (Da), 2,5-Dihydroxyterephthalaldehyde (Dha), and 2,5-Diethoxyterephthalaldehyde (Deta) with different conjugation degrees are selected to condense with 5,10,15,20-Tetrakis(4-aminophenyl)porphyrin (Tph) to synthesize COF-366, DhaTph, and JNU-2, respectively. The higher conjugation of Dha and Deta than Da leads to the higher conjugation of DhaTph and JNU-2, respectively. Moreover, the hydroxyl group in Dha and the ethoxy group in Deta further expand the conjugation of DhaTph and JNU-2 via the formation of intralayer extended π-cloud delocalization and p-π conjunction, respectively. The extension of conjugation for DhaTph and JNU-2 results in the increase of intersystem crossing process and significantly improves their photosensitizing activity. Furthermore, JNU-2 with the highest photosensitizing activity exhibits superior antibacterial effects toward Staphylococcus aureus (99.1%) and Escherichia coli (96.8%). This study offers a new conjugation-regulating strategy for designing high photosensitizing activity of Por-COFs for the inactivation of bacteria.


Assuntos
Estruturas Metalorgânicas , Porfirinas , Antibacterianos/farmacologia , Humanos , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/farmacologia , Staphylococcus aureus
5.
Talanta ; 233: 122610, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34215094

RESUMO

Recently, antibiotic resistant has become a serious public health concern, which warrants new generations of antibiotics to be developed. Pharmacodynamic evaluation is crucial in drug discovery processes. Despite numerous advanced imaging systems are available nowadays, technologies for the sensitive in vivo diagnosis of bacterial infections and direct visualization of drug efficacy are yet to be developed. In this study, we have developed novel near-infrared (NIR) fluorogenic probes. These probes are dark in solution but highly fluorescent when bound to the cognate reporter, fluorogen-activating protein (FAP). We established the in vivo bacterial infection model using FAP_dH6.2 recombinantly expressed E. coli and applied this NIR fluoromodule-based system for diagnosing bacterial infections and monitoring disease progressions and its responses to a type of antibiotics through classic mechanism of membrane lysis. This NIR fluoromodule-based system will discover new information on bacterial infections and identify newer antibacterial entities.


Assuntos
Infecções Bacterianas , Corantes Fluorescentes , Antibacterianos/farmacologia , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/tratamento farmacológico , Escherichia coli/genética , Humanos , Proteínas
6.
Talanta ; 233: 122472, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34215106

RESUMO

Direct identification of bacteria in blood cultures using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is interfered with by a variety of non-bacterial proteins derived from blood cells and culture media. Thus, appropriate pre-treatments are needed for successful identification. Here, the bacteria in blood culture bottles were enriched using co-magnetic beads and processed for MALDI-TOF MS profiling. In this strategy, the Fc-containing mannose-binding lectin-coated Fe3O4 (Fc-MBL@Fe3O4) is incorporated with human IgG-coated Fe3O4 (IgG@Fe3O4) to form co-magnetic beads, which can recognize both Gram-positive and Gram-negative bacteria. Compared to single magnetic beads Fc-MBL@Fe3O4 or IgG@Fe3O4, co-magnetic beads resulted in better bacterial capture efficiency and, therefore, could decrease the false-negative results. Our proposed strategy is much more suitable for enrichment of clinically unknown bacteria from blood culture bottles for MALDI-TOF MS database identification.


Assuntos
Antibacterianos , Hemocultura , Bactérias , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Humanos , Fenômenos Magnéticos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
7.
Mater Sci Eng C Mater Biol Appl ; 127: 112209, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34225861

RESUMO

The design of bioactive plasters is of major interest for the amelioration of dental and bone cements. In this article, a one pot and environmentally friendly strategy based on the addition of a cheap polyphenol-tannic acid (TA) or the main phenolic constituent of TA, namely pyrogallol (PY)- able to interact with calcium sulfate is proposed. Tannic acid and pyrogallol not only modify the morphology of the obtained plaster+TA/PY composites but a part of it is released and provides strong-up to twenty fold- antibacterial effect against Staphylococcus aureus. It is shown that the higher antibacterial efficiency of PY is related to a greater release compared to TA even if in solution the antibacterial effect of PY is lower than that of TA when reported on the basis of the molar concentration in PY units.


Assuntos
Anti-Infecciosos , Taninos , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Sulfato de Cálcio , Pirogalol/farmacologia , Taninos/farmacologia
8.
Mater Sci Eng C Mater Biol Appl ; 127: 112225, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34225870

RESUMO

Many medical and chemical applications require the precise supply of antimicrobial components in a controlled manner at the location of mature biofilm deposits. This work reports a facile strategy to fabricate nanoscale metal-organic frameworks (NMOFs) coencapsulating the antibacterial ligand (lysine carbon dots, Lys-CDs) and targeted drug (folic acid, FA) in one pot to improve antibiofilm efficiency against established biofilms. The resulting products are characterized by transmission electron microscopy, field-emission scanning electron microscopy, powder x-ray diffraction, and ultraviolet-visible spectroscopy. The results show that Lys-CDs could coordinate with Zn2+ and the adding of FA inhibits the coordination of Lys-CDs with central ions of Zn. The Lys-CDs and FA are successfully exposed with the NMOFs disintegrating in the acid environment of bacterial metabolites. We are surprised to find a sharp increase of reactive oxygen species (ROS) inside the bacterial cells by FA functionalizing NMOFs, which undoubtedly enhance the antibacterial and antibiofilm activity. The as-synthesized ZIF-8-based nanocomposites also show the peroxidase-like activity in an acid environment, and produce extremely active hydroxyl radicals resulting in the improved antibacterial and antibiofilm activity. The possible mechanisms of antibacterial activities indicate that the presence of FA is significant in the sense of targeting bacteria. This study shows a novel approach to construct acid stimulation supply system which may be helpful for the research of antibiofilms.


Assuntos
Ácido Fólico , Estruturas Metalorgânicas , Antibacterianos/farmacologia , Bactérias , Biofilmes , Espécies Reativas de Oxigênio
9.
Mater Sci Eng C Mater Biol Appl ; 127: 112227, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34225872

RESUMO

A novel hemostatic nanocomposite (OBC-PDA/PDA-MMT/Ag NPs) was prepared. As Functional hemostatic particles, hydrochloric acid modified montmorillonite coated with dopamine (PDA-MMT) doped into oxidized bacterial cellulose (OBC). In the presence of carboxyl and dopamine, silver ions (Ag+) were reduced into Ag nanoparticles (Ag NPs) distributed homogeneously on the matrix of PDA-MMT and OBC. Then, dopamine was grafted onto the oxidized bacterial cellulose under the crosslinking effect of 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC). After dopamine was grafted onto the oxidized bacterial cellulose, the interaction between PDA-MMT and the whole material was enhanced, and the flexibility was also improved. OBC-PDA/PDA-MMT/Ag NPs hemostatic sponge have appropriate mechanical strength, broad-spectrum antibacterial properties and excellent biodegradability. The hemostatic sponge with addition of PDA-MMT and Ag NPs is expected to provide functional properties such as rapid hemostasis, bacteriostasis and wound healing. In addition, the hemostatic effect of the compound was confirmed in vivo. The hemostatic sponge showed greater coagulation capacity, higher adherent red blood cells and platelets, and lower blood loss. The results show that hemostatic sponge is a rapid and effective coagulant with good antibacterial properties.


Assuntos
Hemostáticos , Nanopartículas Metálicas , Antibacterianos/farmacologia , Dopamina/farmacologia , Hemostasia , Hemostáticos/farmacologia , Prata/farmacologia
10.
Mater Sci Eng C Mater Biol Appl ; 127: 112241, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34225881

RESUMO

Orthopedic implant is commonly associated with occurrence or relapse of osteomyelitis. This study developed a hydrofluoric acid (HF) cleaned silicon nitride (Si3N4) implant Si3N4_AC for osteomyelitis control and established a rat tibial osteomyelitis model to evaluate its efficacy on eradicating periprosthetic infection and enhancing bone regeneration. In vitro studies revealed Si3N4_AC had improved biocompatibility and inhibited Staphylococcus aureus adhesion. A custom-made Si3N4_AC implant was prepared and inserted into the rat tibia longitudinal cavity inoculated with Staphylococcus aureus. The in vivo bacteriostatic and osteogenic efficacies of Si3N4_AC implant were evaluated by histological, microbiological and Micro-CT analyses and compared with implants of pure Ti and Si3N4 . Si3N4_AC implant group revealed 99.5% inhibition of periprosthetic Staphylococcus aureus compared to the osteomyelitis group after 14 days post-operation. Implant-adhering bacteria density of Si3N4_AC was also much lower than pure Ti and Si3N4. In addition, micro-CT evaluation of peri-implant bone formation under the condition of periprosthetic osteomyelitis after 30 days post-surgery confirmed the osteogenic ability of Si3N4_AC. Taken together, Si3N4_AC can be an effective orthopedic biomaterial to eradicate periprosthetic infection and enhance bone regeneration.


Assuntos
Osteomielite , Infecções Estafilocócicas , Animais , Antibacterianos/farmacologia , Regeneração Óssea , Modelos Animais de Doenças , Ácido Fluorídrico , Osteomielite/tratamento farmacológico , Próteses e Implantes , Ratos , Compostos de Silício/farmacologia , Infecções Estafilocócicas/tratamento farmacológico
11.
Mater Sci Eng C Mater Biol Appl ; 127: 112245, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34225884

RESUMO

Wound healing is a complicated process constituted of four successive physiological stages involving wound bleeding, inflammatory response, cell proliferation and tissue remodeling. During this period, bacteria can easily infect the wound. Therefore, we prepared a novel curcumin-loaded sandwich-like nanofibrous membrane (CSNM) using sequential electrospinning for the hemostasis, antibacterial and accelerate wound healing. The morphology of the nanofibrous membrane was analyzed by SEM. In addition, the water absorption capacity, water vapor transmission rate, water contact-angle, and in vitro drug release were all tested. Then in vitro and in vivo hemostatic experiments demonstrated that CSNM has a good hemostatic effect. Antioxidant effect was assessed by the DPPH radical scavenging method and CSNM presented a high antioxidant activity. Additionally, CSNM demonstrated excellent antibacterial activity by the disk diffusion method. Furthermore, the rat dorsal skin defects model revealed that the CSNM distinctly induced the granulation tissue grew, collagen deposition and epithelial tissue remodeling. Meanwhile, the results of the immunohistochemical staining showed that the CSNM can facilitate the expression of CD31 and TGF-ß in the early stage of the wound, thereby accelerating wound healing. In general, this study proved that the multifunctional CSNM has great potential as wound dressing in wound healing.


Assuntos
Curcumina , Nanofibras , Animais , Antibacterianos/farmacologia , Bandagens , Curcumina/farmacologia , Ratos , Tecnologia , Cicatrização
12.
Mymensingh Med J ; 30(3): 625-632, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34226447

RESUMO

The aim of this study was to find the prevalence of ESBL genes among A. baumannii isolates. In this cross sectional study, 49 Acinetobacter spp. were isolated from various clinical samples from March 2019 to February 2020 conducted in the department of Microbiology, Mymensingh Medical College, Mymensingh, Bangladesh. Clinical samples including endotracheal aspirates, wound swab/pus, urine and blood. A total of 380 samples were analyzed. Growth was obtained in 34.21% of the samples yielding 130 organisms. Out of 130 organisms, 49(37.69%) were Acinetobacter spp. Among 49 Acinetobacter spp, 39(79.59%) were Acinetobacter baumannii which was identified by PCR targeting OXA-51 like gene. Amplification of the ESBL encoding genes, namely CTX-M, TEM, SHV done by molecular technique PCR. The most antibacterial resistance was against ceftriaxone (79.48%) and lower resistance only showed in colistin (12.82%). All the isolates were sensitive to tigecycline. The distribution of ESBLs genes such as TEM 20(51.28%), CTX-M 16(41.02%) and SHV 0(0%). The high resistance to most of the antibiotics among the studied strains and also a high prevalence of TEM gene in A. baumannii strains found in our study gives alarming sign towards the treatment complexity of these strains.


Assuntos
Acinetobacter baumannii , Acinetobacter baumannii/genética , Antibacterianos/farmacologia , Bangladesh/epidemiologia , Estudos Transversais , Humanos , Testes de Sensibilidade Microbiana , Prevalência , Centros de Atenção Terciária , beta-Lactamases/genética
13.
Mymensingh Med J ; 30(3): 725-737, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34226462

RESUMO

Multi-drug resistant Typhoid fever (resistant to previously used chloramphenicol, ampicillin, amoxicillin, and trimethoprim-sulfamethoxazole) has been commonly described in the South East Asia region and a recent report suggests that the salmonella typhi have reduced response to fluoroquinolones (nalidixic acid-resistant). The optimum treatment protocol for this type of serovar has not been established. This study compared different antimicrobial regimens for the treatment of uncomplicated typhoid fever which was conducted in the medicine ward of Dhaka Medical College Hospital (DMCH) and outdoor setting in private practice in Dhaka metropolitan city, Mymensingh and Sylhet town from January 2017 to December 2017. Bangladeshi adults with uncomplicated typhoid fever were included in this an open-label randomized controlled trial. Ciprofloxacin (20mg/kg of body weight/day for 14 days), azithromycin (20mg/kg/day for 14 days), and Cefixime (16mg/kg/day for 14 days) were compared. Of the 81 enrolled patients, 62 were eligible for analysis (61 S. enterica serovar Typhi, 1 Salmonella enterica serovar paratyphi A). Of the S enterica serovar Typhi isolates, 88.7% (55/62) were MDR and 93.5% (58/62) were nalidixic acid resistant (NAR). The clinical cure rate was 62% (13/21) with ciprofloxacin, 71% (15/21) with Cefixime, and 85% (17/20) with azithromycin (p=0.053). The mean (95% confidence interval [CI]) fever clearance time for patients treated with azithromycin (5.8 days [5.1 to 6.5 days]) was shorter than that for patients treated with cefixime (7.1 days [6.2 to 8.1 days]) and ciprofloxacin (8.2 days [7.2 to 9.2 days]) (p<0.001). All three antibiotics were well tolerated. A 7-day course of azithromycin can be successfully used in uncomplicated typhoid fever due to isolates of MDR S enterica serovar Typhi.


Assuntos
Azitromicina , Febre Tifoide , Adulto , Antibacterianos/uso terapêutico , Azitromicina/uso terapêutico , Bangladesh/epidemiologia , Cefixima/uso terapêutico , Ciprofloxacina/uso terapêutico , Humanos , Testes de Sensibilidade Microbiana , Salmonella typhi , Febre Tifoide/tratamento farmacológico , Febre Tifoide/epidemiologia
14.
Front Cell Infect Microbiol ; 11: 668632, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34195099

RESUMO

Antibiotics are essential drugs used to treat pathogenic bacteria, but their prolonged use contributes to the development and spread of drug-resistant microorganisms. Antibiotic resistance is a serious challenge and has led to the need for new alternative molecules less prone to bacterial resistance. Antimicrobial peptides (AMPs) have aroused great interest as potential next-generation antibiotics, since they are bioactive small proteins, naturally produced by all living organisms, and representing the first line of defense against fungi, viruses and bacteria. AMPs are commonly classified according to their sources, which are represented by microorganisms, plants and animals, as well as to their secondary structure, their biosynthesis and their mechanism of action. They find application in different fields such as agriculture, food industry and medicine, on which we focused our attention in this review. Particularly, we examined AMP potential applicability in wound healing, skin infections and metabolic syndrome, considering their ability to act as potential Angiotensin-Converting Enzyme I and pancreatic lipase inhibitory peptides as well as antioxidant peptides. Moreover, we argued about the pharmacokinetic and pharmacodynamic approaches to develop new antibiotics, the drug development strategies and the formulation approaches which need to be taken into account in developing clinically suitable AMP applications.


Assuntos
Peptídeos Catiônicos Antimicrobianos , Preparações Farmacêuticas , Animais , Antibacterianos/uso terapêutico , Bactérias , Proteínas Citotóxicas Formadoras de Poros
15.
Front Cell Infect Microbiol ; 11: 690799, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34211858

RESUMO

In this study, a detailed genetic dissection of the huge and complex bla NDM-carrying genetic elements and their related mobile genetic elements was performed in Enterobacteriaceae. An extensive comparison was applied to 12 chromosomal genetic elements, including six sequenced in this study and the other six from GenBank. These 12 genetic elements were divided into five groups: a novel IME Tn6588; two related IMEs Tn6523 (SGI1) and Tn6589; four related ICEs Tn6512 (R391), Tn6575 (ICEPvuChnBC22), Tn6576, and Tn6577; Tn7 and its derivatives Tn6726 and 40.7-kb Tn7-related element; and two related IMEs Tn6591 (GIsul2) and Tn6590. At least 51 resistance genes, involved in resistance to 18 different categories of antibiotics and heavy metals, were found in these 12 genetic elements. Notably, Tn6576 carried another ICE Tn6582. In particular, the six bla NDM-carrying genetic elements Tn6588, Tn6589, Tn6575, Tn6576, Tn6726, and 40.7-kb Tn7-related element contained large accessory multidrug resistance (MDR) regions, each of which had a very complex mosaic structure that comprised intact or residual mobile genetic elements including insertion sequences, unit or composite transposons, integrons, and putative resistance units. Core bla NDM genetic environments manifested as four different Tn125 derivatives and, notably, two or more copies of relevant Tn125 derivatives were found in each of Tn6576, Tn6588, Tn6589, and 40.7-kb Tn7-related element. The huge and complex bla NDM-carrying genetic elements were assembled from complex transposition and homolog recombination. Firstly identified were eight novel mobile elements, including three ICEs Tn6576, Tn6577, and Tn6582, two IMEs, Tn6588 and Tn6589, two composite transposons Tn6580a and Tn6580b, and one integron In1718.


Assuntos
Infecções por Enterobacteriaceae , Enterobacteriaceae , Antibacterianos/farmacologia , Elementos de DNA Transponíveis , Enterobacteriaceae/genética , Humanos , Integrons/genética , Plasmídeos/genética , beta-Lactamases/genética
16.
Ying Yong Sheng Tai Xue Bao ; 32(6): 2267-2274, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34212633

RESUMO

The spread of antibiotic resistance in soil is a global threat to public health and food safety, challenging the prevention and treatment of human infectious disease. The horizontal transfer of ARGs mediated by bacteriophages (phages) is an important pathway for the spread of antibiotic resistance genes (ARGs). However, the knowledge on the contribution of phages to ARGs transmission in soil is elusive. Here, we reviewed the distribution characteristics of phages in soil and its driving factors. We summarized the main methods for purification and enrichment of soil phage, reviewed recent achievements in the mechanism of phage-mediated horizontal transfer of ARGs in soil and proposed some outstanding questions. This review would contribute to understanding the important ecological role of phages in driving the horizontal transfer of ARGs, and provide a basis for developing management strategies to mitigate ARGs pollution.


Assuntos
Bacteriófagos , Antibacterianos/farmacologia , Bacteriófagos/genética , Resistência Microbiana a Medicamentos/genética , Genes Bacterianos , Humanos , Solo , Microbiologia do Solo
17.
Molecules ; 26(12)2021 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-34201372

RESUMO

A novel pleuromutilin derivative, 22-(4-(2-(4-nitrophenyl-piperazin-1-yl)-acetyl)-piperazin-1-yl)-22-deoxypleuromutilin (NPDM), was synthesized in our laboratory and proved excellent antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). In this study, more methods were used to further study its preliminary pharmacological effect. The antibacterial efficacy and toxicity of NPDM were evaluated using tiamulin as the reference drug. The in vitro antibacterial activity study showed that NPDM is a potent bactericidal agent against MRSA that induced time-dependent growth inhibition and a concentration-dependent post-antibiotic effect (PAE). Toxicity determination showed that the cytotoxicity of NPDM was slightly higher than that of tiamulin, but the acute oral toxicity study proved that NPDM was a low-toxic compound. In an in vivo antibacterial effect study, NPDM exhibited a better therapeutic effect than tiamulin against MRSA in a mouse thigh infection model as well as a mouse systemic infection model with neutropenia. The 50% effective dose (ED50) of NPDM in a Galleria mellonella infection model was 50.53 mg/kg. The pharmacokinetic properties of NPDM were also measured, which showed that NPDM was a rapid elimination drug in mice.


Assuntos
Antibacterianos/farmacologia , Diterpenos/farmacologia , Nitrofenóis/farmacologia , Piperazina/farmacologia , Compostos Policíclicos/farmacologia , Animais , Linhagem Celular , Insetos/microbiologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos ICR , Testes de Sensibilidade Microbiana/métodos , Ratos , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia
18.
Molecules ; 26(13)2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34202191

RESUMO

Twenty-two novel, variously substituted nitroazetidines were designed as both sulfonamide and urethane vinylogs possibly endowed with antimicrobial activity. The compounds under study were obtained following a general procedure recently developed, starting from 4-nitropentadienoates deriving from a common ß-nitrothiophenic precursor. While being devoid of any activity against fungi and Gram-negative bacteria, most of the title compounds performed as potent antibacterial agents on Gram-positive bacteria (E. faecalis and three strains of S. aureus), with the most potent congener being the 1-(4-chlorobenzyl)-3-nitro-4-(p-tolyl)azetidine 22, which displayed potency close to that of norfloxacin, the reference antibiotic (minimum inhibitory concentration values 4 and 1-2 µg/mL, respectively). Since 22 combines a relatively efficient activity against Gram-positive bacteria and a cytotoxicity on eucharyotic cells only at 4-times higher concentrations (inhibiting concentration on 50% of the cultured eukaryotic cells: 36 ± 10 µM, MIC: 8.6 µM), it may be considered as a promising hit compound for the development of a new series of antibacterials selectively active on Gram-positive pathogens. The relatively concise synthetic route described herein, based on widely available starting materials, could feed further structure-activity relationship studies, thus allowing for the fine investigation and optimization of the toxico-pharmacological profile.


Assuntos
Antibacterianos , Azetidinas , Enterococcus faecalis/crescimento & desenvolvimento , Staphylococcus aureus/crescimento & desenvolvimento , Antibacterianos/síntese química , Antibacterianos/química , Antibacterianos/farmacologia , Azetidinas/síntese química , Azetidinas/química , Azetidinas/farmacologia , Relação Dose-Resposta a Droga , Avaliação de Medicamentos , Células Hep G2 , Humanos , Relação Estrutura-Atividade
19.
Molecules ; 26(13)2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34203552

RESUMO

Here, we investigated general porin regulation in Yersinia pseudotuberculosis 488, the causative agent of Far Eastern scarlet-like fever, in response to sublethal concentrations of antibiotics. We chose four antibiotics of different classes and measured gene expression using qRT-PCR and GFP reporter systems. Our data showed temporal regulation of the general porin genes ompF and ompC caused by antibiotic stress. The porin transcription initially decreased, providing early defensive response of the bacterium, while it returned to that of the untreated cells on prolonged antibiotic exposure. Unlike the major porin genes, the transcription of the alternative porin genes ompX and lamB was increased. Moreover, a short-term ompR- and marA-mediated porin regulation was observed. The main finding was a phenotypic heterogeneity of Y. pseudotuberculosis population manifested in variable porin gene expression under carbenicillin exposure. This may offer adaptive fitness advantages for a particular bacterial subpopulation.


Assuntos
Antibacterianos/farmacologia , Proteínas de Bactérias/biossíntese , Carbenicilina/farmacologia , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Porinas/biossíntese , Estresse Fisiológico/efeitos dos fármacos , Yersinia pseudotuberculosis/metabolismo
20.
Molecules ; 26(11)2021 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-34205002

RESUMO

Numerous chemical compounds of high practical importance, such as drugs, fertilizers, and food additives are being commercialized as racemic mixtures, although in most cases only one of the isomers possesses the desirable properties. As our understanding of the biological actions of chiral compounds has improved, the investigation of the pharmacological and toxicological properties has become more and more important. Chirality has become a major issue in the pharmaceutical industry; therefore, there is a continuous demand to extend the available analytical methods for enantiomeric separations and enhance their efficiency. Direct liquid chromatography methods based on the application of chiral stationary phases have become a very sophisticated field of enantiomeric separations by now. Hundreds of chiral stationary phases have been commercialized so far. Among these, macrocyclic glycopeptide-based chiral selectors have proved to be an exceptionally useful class of chiral selectors for the separation of enantiomers of biological and pharmacological importance. This review focuses on direct liquid chromatography-based enantiomer separations, applying macrocyclic glycopeptide-based chiral selectors. Special attention is paid to the characterization of the physico-chemical properties of these macrocyclic glycopeptide antibiotics providing detailed information on their applications published recently.


Assuntos
Antibacterianos/química , Glicopeptídeos/química , Compostos Macrocíclicos/química , Cromatografia Líquida , Estrutura Molecular , Fenômenos Físicos , Estereoisomerismo
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