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1.
J Agric Food Chem ; 70(18): 5570-5578, 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35499918

RESUMO

Antimicrobial compounds from the commensal gut microbiota have gained much attention due to their multifunctionality in maintaining good health in the host and killing multidrug-resistant bacteria. Our previous study showed that Paenibacillus jilinensis YPG26 isolated from chicken intestine can antagonize multiple pathogens. Herein, we characterized a bacteriocin-like inhibitory substance, jileicin, purified from P. jilinensis YPG26. Mass spectrometry analysis revealed that jileicin was a protein consisting of 211 amino acids, which showed 88.98% identity to the SIMPL domain-containing protein. The jileicin showed a relatively broad-spectrum antibacterial ability, especially against enterococci. Additionally, the jileicin exhibited good stability after various treatments, no detectable resistance, no significant cytotoxicity, and very low levels of hemolytic activity. The mode of action against Enterococcus faecium demonstrated that jileicin could destroy cell membrane integrity, increase cell membrane permeability, and eventually lead to cell death. Furthermore, jileicin was efficient in controlling the growth of E. faecium in milk. In conclusion, jileicin, as a newly identified antibacterial agent, is expected to be a promising candidate for application in the food, pharmaceutical, and biomedical industries.


Assuntos
Bacteriocinas , Enterococcus faecium , Paenibacillus , Antibacterianos/metabolismo , Enterococcus , Enterococcus faecium/metabolismo , Paenibacillus/genética
2.
PLoS One ; 17(5): e0266742, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35536836

RESUMO

Pseudomonas aeruginosa has different resistant mechanisms including the constitutive MexAB-OprM efflux pump. Single nucleotide polymorphisms (SNPs) in the mexR, nalC, and nalD repressors of this efflux pump can contribute to antimicrobial resistance; however, it is unknown whether these changes are mainly related to genetic lineages or environmental pressure. This study identifies SNPs in the mexR, nalC, and nalD genes in clinical and environmental isolates of P. aeruginosa (including high-risk clones). Ninety-one P. aeruginosa strains were classified according to their resistance to antibiotics, typified by multilocus sequencing, and mexR, nalC, and nalD genes sequenced for SNPs identification. The mexAB-oprM transcript expression was determined. The 96.7% of the strains were classified as multidrug resistant. Eight strains produced serine carbapenemases, and 11 strains metallo-ß-lactamases. Twenty-three new STs and high-risk clones ST111 and ST233 were identified. SNPs in the mexR, nalC, and nalD genes revealed 27 different haplotypes (patterns). Sixty-two mutational changes were identified, 13 non-synonymous. Haplotype 1 was the most frequent (n = 40), and mainly identified in strains ST1725 (33/40), with 57.5% pan drug resistant strains, 36.5% extensive drug resistant and two strains exhibiting serin-carbapenemases. Haplotype 12 (n = 9) was identified in ST233 and phylogenetically related STs, with 100% of the strains exhibiting XDR and 90% producing metallo-ß-lactamases. Haplotype 5 was highly associated with XDR and related to dead when compared to ST1725 and ST233 (RRR 23.34; p = 0.009 and RRR 32.01; p = 0.025). A significant relationship between the mexR-nalC-nalD haplotypes and phylogenetically related STs was observed, suggesting mutational changes in these repressors are highly maintained within genetic lineages. In addition, phylogenetically related STs showed similar resistant profiles; however, the resistance was (likely or partly) attributed to the MexAB-OprM efflux pump in 56% of the strains (only 45.05% showed mexA overtranscription), in the remaining strains the resistance could be attributed to carbapenemases or mechanisms including other pumps, since same SNPs in the repressor genes gave rise to different resistance profiles.


Assuntos
Nucleotídeos , Pseudomonas aeruginosa , Antibacterianos/metabolismo , Proteínas da Membrana Bacteriana Externa/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Genes Reguladores , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Testes de Sensibilidade Microbiana , Nucleotídeos/metabolismo , Pseudomonas aeruginosa/metabolismo , beta-Lactamases/genética
3.
Proc Natl Acad Sci U S A ; 119(19): e2114214119, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35500116

RESUMO

SignificanceThe increase in multidrug-resistant bacteria highlights the urgent need for compounds with novel target sites that can be developed as antibiotics. The argyrins represent a family of naturally produced octapeptides that display promising activity against Pseudomonas aeruginosa by inhibiting protein synthesis. Our structural and kinetic analyses reveal that argyrins inhibit protein synthesis by interacting with, and trapping, the translation elongation factor G (EF-G) on the ribosome, analogous to that reported previously for the unrelated antibiotic fusidic acid. However, the binding site of argyrin on EF-G is distinct from that of fusidic acid, indicating that intramolecular movements at the domain III/V interface of EF-G are also essential for facilitating late events in the translocation mechanism.


Assuntos
Antibacterianos , Fator G para Elongação de Peptídeos , Antibacterianos/metabolismo , Ácido Fusídico/farmacologia , Humanos , Oligopeptídeos , Fator G para Elongação de Peptídeos/metabolismo , Ribossomos/metabolismo , Translocação Genética
4.
Microbiology (Reading) ; 168(5)2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35536738

RESUMO

Vibrio parahaemolyticus is a shellfish-borne pathogen that is a highly prevalent causative agent of inflammatory gastroenteritis in humans. Genomic libraries have proven useful for the identification of novel gene functions in many bacterial species. In this study we prepared a library containing 40 kb fragments of randomly sheared V. parahaemolyticus genomic DNA and introduced this into Escherichia coli HB101 using a commercially available low copy cosmid system. In order to estimate coverage and suitability of the library and potentially identify novel antimicrobial resistance determinants, we screened for the acquisition of resistance to the fluoroquinolone norfloxacin - a phenotype exhibited by V. parahaemolyticus but not the heterologous E. coli host. Upon selection on solid medium containing norfloxacin, 0.52% of the library population was resistant, consistent with the selection of a single resistance locus. End-sequencing identified six distinct insert fragments. All clones displayed fourfold increased norfloxacin MIC compared with E. coli HB101 carrying an empty vector. The common locus contained within resistant clones included qnr, a previously described quinolone resistance gene. These results indicate that the library was unbiased, of sufficient coverage and that heterologous expression was possible. While we hope that this library proves useful for identifying the genetic determinants of complex phenotypes such as those related to virulence, not all norfloxacin resistance genes were detected in our screen. As such, we discuss the benefits and limitations of this approach for identifying the genetic basis of uncharacterized bacterial phenotypes.


Assuntos
Quinolonas , Vibrio parahaemolyticus , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Farmacorresistência Bacteriana/genética , Escherichia coli/genética , Biblioteca Genômica , Norfloxacino/metabolismo , Norfloxacino/farmacologia , Quinolonas/metabolismo , Quinolonas/farmacologia , Vibrio parahaemolyticus/metabolismo
5.
PLoS One ; 17(5): e0268072, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35511780

RESUMO

Pseudomonas strain NCIMB10586, in the P. fluorescens subgroup, produces the polyketide antibiotic mupirocin, and has potential as a host for industrial production of a range of valuable products. To underpin further studies on its genetics and physiology, we have used a combination of standard and atypical approaches to achieve a quality of the genome sequence and annotation, above current standards for automated pathways. Assembly of Illumina reads to a PacBio genome sequence created a retrospectively hybrid assembly, identifying and fixing 415 sequencing errors which would otherwise affect almost 5% of annotated coding regions. Our annotation pipeline combined automation based on related well-annotated genomes and stringent, partially manual, tests for functional features. The strain was close to P. synxantha and P. libaniensis and was found to be highly similar to a strain being developed as a weed-pest control agent in Canada. Since mupirocin is a secondary metabolite whose production is switched on late in exponential phase, we carried out RNAseq analysis over an 18 h growth period and have developed a method to normalise RNAseq samples as a group, rather than pair-wise. To review such data we have developed an easily interpreted way to present the expression profiles across a region, or the whole genome at a glance. At the 2-hour granularity of our time-course, the mupirocin cluster increases in expression as an essentially uniform bloc, although the mupirocin resistance gene stands out as being expressed at all the time points.


Assuntos
Mupirocina , Pseudomonas fluorescens , Antibacterianos/metabolismo , Anotação de Sequência Molecular , Pseudomonas fluorescens/genética , Estudos Retrospectivos , Análise de Sequência de DNA/métodos
6.
Arch Microbiol ; 204(6): 297, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35508818

RESUMO

The depletion of dissolved oxygen in a defined synthetic medium can be measured in real time, using a micro-well plate format, associated with a fluorescent plate reader. This technology is appropriate for investigating the effect of antibiotics on cell kinetics because there is a direct correlation between the latter and the amount of dissolved oxygen in the medium of an assay. In this study, the metabolic activity of the opportunistic human pathogen Pseudomonas aeruginosa PA01 was investigated using the OxoPlate OP96U optical sensor technology. The response of P. aeruginosa to aminoglycoside antibiotics when Ca2+and Mg2+ ions are present in the Evans defined synthetic medium was measured. The results revealed that the effect of antibiotics on P. aeruginosa is influenced by the concentration of divalent cations present in the test medium, although the efficiency of Ca2+ in supressing antibiotic activity was found to be greater than that of Mg2+. By comparison to tobramycin, the effect of amikacin is largely inhibited by the Ca2+and Mg2+concentrations. The study results underscore that the reliability of the observation of growth inhibitors is enhanced by the oxygen consumption measurements. Thus, the OxoPlate OP96U system is proven to be an accurate method to test the effectiveness of antibiotic treatments against P. aeruginosa.


Assuntos
Antibacterianos , Pseudomonas aeruginosa , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Cátions Bivalentes/metabolismo , Cátions Bivalentes/farmacologia , Humanos , Testes de Sensibilidade Microbiana , Oxigênio/metabolismo , Reprodutibilidade dos Testes , Tobramicina/metabolismo , Tobramicina/farmacologia
7.
J Antibiot (Tokyo) ; 75(6): 341-353, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35440769

RESUMO

Antibiotic use provides a promising strategy for the treatment of non-alcoholic fatty liver disease (NAFLD) by regulating the gut microbiota composition. Triclosan, a widely used antibiotic, may improve gut microbiome dysbiosis associated with NAFLD through the suppression of pathogenic gram-negative bacteria. However, the effects of triclosan on gut microbiota and hepatic steatosis and have not been explored in NAFLD mouse model. In this study, C57BL/6J mice were fed with high fat diet (HFD) for continuous 20 weeks and treated with triclosan at 400 mg/kg/d for 8 weeks from week 13. We explored the effects of triclosan on hepatic lipid accumulation and gut microbiome in HFD-fed mice by histological examination and 16 S ribosomal RNA sequencing, respectively. Analysis on the composition of gut microbiota indicated that triclosan suppressed pathogenic gram-negative bacteria, including Helicobacter, Erysipelatoclostridium and Citrobacter, and increased the ratio of Bacteroidetes/Firmicutes in HFD-fed mice. Meanwhile, triclosan increased the relative abundance of beneficial gut microbiomes including Lactobacillus, Bifidobacterium and Lachnospiraceae, which protected against metabolic abnormality. The results of alpha-diversity and beta-diversity also showed the improvement of triclosan on bacterial diversity and richness in HFD-fed mice. Pathway analysis further confirmed that triclosan can regulate nutrient and energy metabolism through the elimination of deleterious bacteria. As a result, triclosan intervention significantly reduced lipid accumulation and alleviated hepatic steatosis in HFD-fed mice. In conclusion, our results suggest that triclosan can alleviate liver steatosis in HFD-fed mice by targeting the gut microbiome.


Assuntos
Microbioma Gastrointestinal , Hepatopatia Gordurosa não Alcoólica , Triclosan , Animais , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Bactérias/genética , Dieta Hiperlipídica/efeitos adversos , Microbioma Gastrointestinal/genética , Lipídeos , Fígado/metabolismo , Fígado/patologia , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/microbiologia , Triclosan/farmacologia
8.
Biochim Biophys Acta Biomembr ; 1864(8): 183935, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35461827

RESUMO

Ciprofloxacin (CPX), a second generation fluoroquinolone antibiotic, is used as a primary antibiotic for treatment against gastroenteritis, drug-resistant tuberculosis, and malignant otitis externa. CPX is a broad spectrum antibiotic that targets the DNA gyrase of both Gram-positive and Gram-negative bacteria. Irrational and improper usage of CPX results in emergence of CPX resistant organisms emphasizing the importance of using lethal doses of CPX. Here, we have systematically analysed the effect of CPX at sub lethal concentrations on live E. coli membrane and growth dynamics. As a result of CPX interaction at sub-lethal concentrations, we detected filamentation of the bacterial cells during cell division. Although CPX is a DNA targeting antibiotic and did not result in considerable increase of live E. coli cell surface roughness, we observed significant enhancement in the lipid diffusion coefficients possibly due to disrupted lipid packing or altered lipid composition. Interestingly, we seem to observe slightly higher extent of lipid diffusion alteration when bacterial inner membrane specific label FM4-64 was used in comparison to the non-specific membrane dye. Both these results are contrary to that observed in bacterial cells for colistin, a membrane targeting antibiotics. Our work highlights the need for using multiple, complementary surface and depth sensitive techniques to obtain information on the realistic nature of bacterial cell membrane remodelling due to non-membrane targeting antibiotics. Our work could have implications for identification of potential biomembrane markers at sub-lethal concentrations even for antibiotics which are non-membrane targeting that could help in unravelling pathways for emergence of antimicrobial resistance.


Assuntos
Ciprofloxacina , Escherichia coli , Antibacterianos/metabolismo , Bactérias , Membrana Celular , Ciprofloxacina/metabolismo , Ciprofloxacina/farmacologia , Ciprofloxacina/uso terapêutico , Escherichia coli/metabolismo , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Lipídeos/farmacologia
9.
Front Cell Infect Microbiol ; 12: 866900, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35433501

RESUMO

The concept of antimicrobial lipids as effectors of innate host defense is an emerging field. There is limited knowledge on the antimicrobial role of lipids in the ocular environment. Tears act as first line of defense to protect the ocular surface from infections. Antimicrobial effects of tear lipids have been demonstrated using meibomian lipids that are the source of majority of lipids in tears. This article describes the knowledge available on the antimicrobial role of tear lipids at the ocular surface and the antimicrobial potential of various lipid classes present in tears that can contribute to antimicrobial protection of the eye. Like other mucosal secretions, tears contain many proteins and lipids with known antimicrobial effects. The antimicrobial defense of tears is far stronger than can be demonstrated by the effects of individual compounds many of which are present in low concentrations but synergistic and additive interactions between them provide substantial antimicrobial protection to the ocular surface. It is inferred that antimicrobial lipids play important role in innate defense of tears, and cooperative interactions between various antimicrobial lipids and proteins in tears provide a potent host defense mechanism that is effective against a broad spectrum of pathogens and renders self-sterilizing properties to tears for keeping the microbial load low at the ocular surface.


Assuntos
Anti-Infecciosos , Lágrimas , Antibacterianos/metabolismo , Anti-Infecciosos/metabolismo , Anti-Infecciosos/farmacologia , Lipídeos , Glândulas Tarsais/metabolismo
10.
Microbiology (Reading) ; 168(4)2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35438625

RESUMO

Microcins are an understudied and poorly characterized class of antimicrobial peptides. Despite the existence of only 15 examples, all identified from the Enterobacteriaceae, microcins display diversity in sequence, structure, target cell uptake, cytotoxic mechanism of action and target specificity. Collectively, these features describe some of the unique means nature has contrived for molecules to cross the 'impermeable' barrier of the Gram-negative bacterial outer membrane and inflict cytotoxic effects. Microcins appear to be widely dispersed among different species and in different environments, where they function in regulating microbial communities in diverse ways, including through competition. Growing evidence suggests that microcins may be adapted for therapeutic uses such as antimicrobial drugs, microbiome modulators or facilitators of peptide uptake into cells. Advancing our biological, ecological and biochemical understanding of the roles of microcins in bacterial interactions, and learning how to regulate and modify microcin activity, is essential to enable such therapeutic applications.


Assuntos
Antibacterianos , Bacteriocinas , Sequência de Aminoácidos , Antibacterianos/metabolismo , Bactérias/metabolismo , Bacteriocinas/metabolismo , Enterobacteriaceae/metabolismo
11.
Microbiology (Reading) ; 168(4)2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35467499

RESUMO

Despite renewed interest, development of chemical biology methods to study peptidoglycan metabolism has lagged in comparison to the glycobiology field in general. To address this, a panel of diamides were screened against the Gram-positive bacterium Streptococcus pneumoniae to identify inhibitors of bacterial growth. The screen identified the diamide masarimycin as a bacteriostatic inhibitor of S. pneumoniae growth with an MIC of 8 µM. The diamide inhibited detergent-induced autolysis in a concentration-dependent manner, indicating perturbation of peptidoglycan degradation as the mode-of-action. Cell based screening of masarimycin against a panel of autolysin mutants, identified a higher MIC against a ΔlytB strain lacking an endo-N-acetylglucosaminidase involved in cell division. Subsequent biochemical and phenotypic analyses suggested that the higher MIC was due to an indirect interaction with LytB. Further analysis of changes to the cell surface in masarimycin treated cells identified the overexpression of several moonlighting proteins, including elongation factor Tu which is implicated in regulating cell shape. Checkerboard assays using masarimycin in concert with additional antibiotics identified an antagonistic relationship with the cell wall targeting antibiotic fosfomycin, which further supports a cell wall mode-of-action.


Assuntos
Peptidoglicano , Streptococcus pneumoniae , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Parede Celular/metabolismo , Diamida/metabolismo , N-Acetil-Muramil-L-Alanina Amidase/genética , N-Acetil-Muramil-L-Alanina Amidase/metabolismo , Peptidoglicano/metabolismo , Streptococcus pneumoniae/metabolismo
12.
mBio ; 13(2): e0038522, 2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35377167

RESUMO

Toxin-antitoxin systems are genetic elements that are widespread in prokaryotes. Although molecular mode of action of many of these toxins has been identified, their biological functions are mostly unknown. We investigated the functional integration of the TisB/IstR toxin-antitoxin system in the Escherichia coli SOS genotoxic stress response network. We showed that the tisB gene is induced in cells exposed to high doses of the genotoxic antibiotic trimethoprim. However, we also found that TisB contributes to trimethoprim-induced lethality. This is a consequence of the TisB-induced drop in the proton motive force (PMF), which results in blocking the thymine import and therefore the functioning of the pyrimidine salvage pathway. Conversely, a TisB-induced PMF drop protects cells by preventing the import of some other toxic compounds, like the aminoglycoside antibiotic gentamicin and colicin M, in the SOS-induced cells. Colicins are cytotoxic molecules produced by Enterobacterales when they are exposed to strong genotoxic stresses in order to compete with other microbiota members. We indeed found that TisB contributes to E. coli's fitness during mouse gut colonization. Based on the results obtained here, we propose that the primary biological role of the TisB toxin is to increase the probability of survival and maintenance in the mammalian gut of their bacterial hosts when they have to simultaneously deal with massive DNA damages and a fierce chemical warfare with other microbiota members. IMPORTANCE The contribution of toxin-antitoxin systems to the persistence of bacteria to antibiotics has been intensively studied. This is also the case with the E. coli TisB/IstR toxin-antitoxin system, but the contribution of TisB to the persistence to antibiotics turned out to be not as straightforward as anticipated. In this study, we show that TisB can decrease, but also increase, cytotoxicity of different antibiotics. This inconsistency has a common origin, i.e., TisB-induced collapse of the PMF, which impacts the import and the action of different antibiotics. By taking into account the natural habitat of TisB bacterial hosts, the facts that this toxin-antitoxin system is integrated into the genotoxic stress response regulon SOS and that both SOS regulon and TisB are required for E. coli to colonize the host intestine, and the phenotypic consequences of the collapse of the PMF, we propose that TisB protects its hosts from cytotoxic molecules produced by competing intestinal bacteria.


Assuntos
Colicinas , Infecções por Escherichia coli , Animais , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Colicinas/genética , Dano ao DNA , Escherichia coli/metabolismo , Mamíferos , Camundongos , Trimetoprima
13.
Molecules ; 27(8)2022 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-35458637

RESUMO

Quorum sensing (QS) is a cell-to-cell communication process that controls bacterial collective behaviors. The QS network regulates and coordinates bacterial virulence factor expression, antibiotic resistance and biofilm formation. Therefore, inhibition of the QS system is an effective strategy to suppress the bacterial virulence. Herein, we identify a phosphate ester derivative of chrysin as a potent QS inhibitor of the human pathogen Pseudomonas aeruginosa (P. aeruginosa) using a designed luciferase reporter assay. In vitro biochemical analysis shows that the chrysin derivative binds to the bacterial QS regulator LasR and abrogates its DNA-binding capability. In particular, the derivative exhibits higher anti-virulence activity compared to the parent molecule. All the results reveal the potential application of flavone derivative as an anti-virulence compound to combat the infectious diseases caused by P. aeruginosa.


Assuntos
Flavonas , Percepção de Quorum , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Proteínas de Bactérias/metabolismo , Biofilmes , Flavonas/metabolismo , Flavonas/farmacologia , Humanos , Pseudomonas aeruginosa , Fatores de Virulência/metabolismo
14.
Molecules ; 27(8)2022 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-35458685

RESUMO

The increase in ß-lactam-resistant Gram-negative bacteria is a severe recurrent problem in the food industry for both producers and consumers. The development of nanotechnology and nanomaterial applications has transformed many features in food science. The antibacterial activity of zinc oxide nanoparticles (ZnO NPs) and their mechanism of action on ß-lactam-resistant Gram-negative food pathogens, such as Escherichia coli, Pseudomonas aeruginosa, Salmonella typhi, Serratia marcescens, Klebsiella pneumoniae, and Proteus mirabilis, are investigated in the present paper. The study results demonstrate that ZnO NPs possesses broad-spectrum action against these ß-lactamase-producing strains. The minimal inhibitory and minimal bactericidal concentrations vary from 0.04 to 0.08 and 0.12 to 0.24 mg/mL, respectively. The ZnO NPs elevate the level of reactive oxygen species (ROS) and malondialdehyde in the bacterial cells as membrane lipid peroxidation. It has been confirmed from the transmission electron microscopy image of the treated bacterial cells that ZnO NPs diminish the permeable membrane, denature the intracellular proteins, cause DNA damage, and cause membrane leakage. Based on these findings, the action of ZnO NPs has been attributed to the fact that broad-spectrum antibacterial action against ß-lactam-resistant Gram-negative food pathogens is mediated by Zn2+ ion-induced oxidative stress, actions via lipid peroxidation and membrane damage, subsequently resulting in depletion, leading to ß-lactamase enzyme inhibition, intracellular protein inactivation, DNA damage, and eventually cell death. Based on the findings of the present study, ZnO NPs can be recommended as potent broad-spectrum antibacterial agents against ß-lactam-resistant Gram-negative pathogenic strains.


Assuntos
Nanopartículas Metálicas , Nanopartículas , Óxido de Zinco , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Bactérias , Escherichia coli , Testes de Sensibilidade Microbiana , Óxido de Zinco/metabolismo , Óxido de Zinco/farmacologia , beta-Lactamases/metabolismo , beta-Lactamas/metabolismo
15.
Biomed Res Int ; 2022: 8691261, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35372582

RESUMO

The present study is aimed at evaluating the haematobiochemical and immune system alterations in rabbit's exposure to amoxicillin. Thirty-two healthy rabbits were randomly divided into four (n = 8) groups comprising of three experimental groups and one control group. After 7 days of the acclimatization period, the study animals were given different doses of amoxicillin orally (100, 150, and 200 mg/kg body weight) for 21 days. The hematological results revealed that red blood cells, hemoglobin, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration decreased significantly (P < 0.05) whereas white blood cells, neutrophils, and granulocyte exhibited a significantly increasing trend. Serum biochemical analysis showed a significantly increased concentration of HDL, LDL, serum globulin cholesterol, triglyceride, urea, uric acid, creatine, and calcium while plasma fibrinogen, blood sugar, albumin, and total protein were decreased significantly. Furthermore, liver function enzymes such as alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and bilirubin significantly increased. Antioxidant enzymes and oxidative stress parameters such as malondialdehyde concentrations (MDA) increased significantly while catalase, superoxide dismutase, reduced glutathione, and peroxidase reduced significantly in antibiotic amoxicillin-treated groups as compared to the untreated control group (P < 0.05). Microscopic histopathological examination showed negative structural changes in liver, kidney, and heart tissues due to karyorrhexis; a disorganized hepatic cord in the liver; increased Bowman's space, necrotic renal tubules, and degenerative glomerulus in the kidney; and necrotic cardiac cells and cytoplasmic vacuolization in the heart, in antibiotic amoxicillin-treated rabbit groups as compared to the control group. In conclusion, amoxicillin induced stress and physiological and immunological impairments due to the adverse effects on haematobiochemical parameters and histopathological and tissue protein changes in target animals.


Assuntos
Amoxicilina , Antioxidantes , Amoxicilina/efeitos adversos , Animais , Antibacterianos/efeitos adversos , Antibacterianos/metabolismo , Antioxidantes/farmacologia , Sistema Imunitário , Fígado/patologia , Estresse Oxidativo , Coelhos
16.
Front Cell Infect Microbiol ; 12: 866357, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35419296

RESUMO

To discover novel microbial pesticide for controlling rice bacterial disease, polymyxin B1 and E2 were firstly isolated from the supernatant of fermentation broth of Paenibacillus polymyxa Y-1 by bioactivity tracking separation. It is shown that polymyxin B1 and E2 had remarkable in vitro inhibitory activities to Xanthomonas oryzae pv. oryzae (Xoo) and Xanthomonas oryzae pv. oryzicola (Xoc) with the EC50 values of 0.19 µg/ml and 0.21 µg/ml against Xoo, and 0.32 µg/ml and 0.41 µg/ml against Xoc, respectively, which were better than those of Zhongshengmycin (0.31 µg/ml and 0.73 µg/ml) and Bismerthiazol (77.48 µg/ml and 85.30 µg/ml). Polymyxins B1 and E2 had good protection and curative activities against rice bacterial leaf blight (BLB) and rice bacterial leaf streak (BLS) in vivo. The protection and curative activities of polymyxins B1 (45.8 and 35.8%, respectively) and E2 (41.2 and 37.0%, respectively) to BLB were superior to those of Zhongshengmycin (34.8 and 29.8%, respectively) and Bismerthiazol (38.0 and 33.5%, respectively). Meanwhile, the protection and curative activities of polymyxins B1 (44.8 and 39.8%, respectively) and E2 (42.9 and 39.9%, respectively) to BLS were also superior to those of Zhongshengmycin (39.7 and 32.0%, respectively) and Bismerthiazol (41.5 and 34.3%, respectively). Polymyxin B1 exerted the anti-pesticide properties via destroying the cell integrity of Xoo, reducing its infectivity and enhancing rice resistance against pathogens through activating the phenylpropanoid biosynthesis pathway of rice. It is indicated that polymyxin B1 and E2 were potential microbial pesticides for controlling rice bacterial disease.


Assuntos
Infecções Bacterianas , Oryza , Paenibacillus polymyxa , Xanthomonas , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Oryza/microbiologia , Paenibacillus polymyxa/genética , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Polimixinas/análogos & derivados , Polimixinas/metabolismo , Xanthomonas/metabolismo
17.
Sci Rep ; 12(1): 5609, 2022 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-35379875

RESUMO

The outer membrane of Gram-negative bacteria functions as an impermeable barrier to foreign compounds. Thus, modulating membrane transport can contribute to improving susceptibility to antibiotics and efficiency of bioproduction reactions. In this study, the cellular uptake of hydrophobic and large-scaffold antibiotics and other compounds in Gram-negative bacteria was investigated by modulating the homolog expression of bamB encoding an outer membrane lipoprotein and tolC encoding an outer membrane efflux protein via gene deletion and gene silencing. The potential of deletion mutants for biotechnological applications, such as drug screening and bioproduction, was also demonstrated. Instead of being subjected to gene deletion, wild-type bacterial cells were treated with cell-penetrating peptide conjugates of a peptide nucleic acid (CPP-PNA) against bamB and tolC homologs as antisense agents. Results revealed that the single deletion of bamB and tolC in Escherichia coli increased the uptake of large- and small-scaffold hydrophobic compounds, respectively. A bamB-and-tolC double deletion mutant had a higher uptake efficiency for certain antibiotics and other compounds with high hydrophobicity than each single deletion mutant. The CPP-PNA treated E. coli and Pseudomonas aeruginosa cells showed high sensitivity to various antibiotics. Therefore, these gene deletion and silencing approaches can be utilized in therapeutic and biotechnological fields.


Assuntos
Proteínas de Escherichia coli , Escherichia coli , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Transporte Biológico , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/metabolismo
18.
Environ Pollut ; 305: 119299, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35430309

RESUMO

Contamination by tetracycline residues has adverse influences on the environment and is considered a pressing issue. Biodegradation is regarded as a promising way to treat tetracycline residues in the environment. Here, strain Sphingobacterium mizutaii S121, which could degrade 20 mg/L tetracycline completely within 5 days, was isolated from contaminated soil. The characteristics of tetracycline degradation by strain S121 were investigated under various culture conditions. Response surface methodology was used to predict the maximum tetracycline degradation ratio, which can be obtained under the following conditions: 31.36 °C, pH of 7.15, and inoculum volume of 5.5% (v/v). Furthermore, extracellular tetracycline biodegradation products and intracellular metabolic pathways of S121 were detected by ultraperformance liquid chromatography-quadrupole-time-of-flight-mass spectrometry (UPLC-Q-TOF-MS) and UHPLC-quadrupole electrospray (QE)-MS, respectively. The results identified eight possible degradation products, and three putative degradation pathways were proposed. In addition, exposure to tetracycline produced significant influences on metabolic pathways such as pyrimidine, purine, taurine and hypotaurine metabolism and lysine degradation. Consequently, the intracellular metabolic pathway response of S121 in the presence of tetracycline was proposed. These findings are presented for the first time, which will facilitate a comprehensive understanding of the mechanism of tetracycline degradation. Moreover, strain S121 can be a promising bacterium for tetracycline bioremediation.


Assuntos
Sphingobacterium , Tetraciclina , Antibacterianos/metabolismo , Biodegradação Ambiental , Metabolômica , Sphingobacterium/metabolismo , Tetraciclina/análise
19.
Environ Pollut ; 305: 119321, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35439597

RESUMO

Aquatic organisms such as fish can accumulate high levels of arsenic (As) and transform toxic inorganic As (iAs) to non-toxic arsenobetaine (AsB). Whether the gut microbiota are involved in the process of As accumulation and transformation in fish is unclear. Herein, we subjected tilapia (Oreochromis mossambicus) to antibiotic treatment for 19 d to remove the gut microbiota, followed by the dietary exposure to arsenate (As(V)) for 16 d. The antibiotic-treated fish accumulated significantly less total As and AsB levels in the intestine and muscle than the fish in the control group. The gut contents (mixture of microbiota, digestive fluid, and diet debris) in the control fish metabolized As(V) to arsenite (As(III)) and organoarsenicals in vitro, while those in the antibiotic-treated fish lost this ability. As(V) exposure significantly changed the fish gut microbiota community. Stenotrophomonas maltophilia was found to be the dominant species (>60% of total operational taxonomic unit (OTU) number) in the gut microbiota of As-treated fish. The isolated As-resistant strain S. maltophilia SCSIOOM owned a high capability to metabolize As(V) to As(III) and organoarsenicals. Overall, these results demonstrated that the gut microbiota, at least the As-resistant bacteria, were involved in As biotransformation pathways in fish.


Assuntos
Arsênio , Microbioma Gastrointestinal , Tilápia , Poluentes Químicos da Água , Animais , Antibacterianos/metabolismo , Arsênio/metabolismo , Bioacumulação , Biotransformação , Tilápia/metabolismo , Poluentes Químicos da Água/toxicidade
20.
Food Funct ; 13(9): 5050-5060, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35403637

RESUMO

Due to the rapid evolution of antibiotic resistance in Staphylococcus aureus, antivirulence therapy may be a promising alternative for the effective control of the spread of resistant pathogens. The Chinese Materia Medica has been widely used for the treatment of diseases and production of health foods, and it remains a valuable resource for the discovery of compounds possessing antivirulence activity. Through a Caenorhabditis elegans infection model, an EtOAc-soluble fraction of 80% EtOH extract of Salvia miltiorrhiza Bunge (SMEA) was found to possess potential anti-infective activity against S. aureus. Then, several in vitro assays indicated that SMEA had robust antivirulence activity at the dose of 400 µg mL-1, reducing hemolytic activity and α-hemolysin expression in S. aureus. Furthermore, at 100 mg kg-1, SMEA reduced abscess formation in the main organs of mice challenged with S. aureus. In order to identify the bioactive components of SMEA and investigate the mechanisms underlying the antivirulence activity, SMEA was separated using bioassay-guided fractionation. As a result, eight compounds were identified in SMEA. Among them, tanshinone IIB (TNB) showed strong antivirulence activity both in vitro and in vivo. Furthermore, at 24 µg mL-1, TNB significantly reduced the expression of RNAIII and psmα, indicating that the mechanism underlying TNB activity was related to the accessory gene regulator quorum sensing system. In conclusion, TNB's antivirulence properties make it a promising candidate for drug development against S. aureus infections.


Assuntos
Anti-Infecciosos , Salvia miltiorrhiza , Infecções Estafilocócicas , Animais , Antibacterianos/metabolismo , Anti-Infecciosos/farmacologia , Camundongos , Percepção de Quorum , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus , Virulência
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