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1.
J Hazard Mater ; 441: 129861, 2023 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-36063713

RESUMO

A novel strain, Nitratireductor sp. GZWM139 capable of efficient removal of SMX was isolated from mariculture sewage, and Nitratireductor was reported to conduct the removal of antibiotics for the first time. Strain GZWM139 exhibited desirable adaptations to environmental factors with SMX removal efficiencies more than 90 % at temperatures of 28-38 °C, pH values of 4.5-8.5, salinities of 20-30 ‰, SMX levels of 1-5 mg/L and shaking speeds of 20-260 rpm. SMX removal was a cooperated process implemented by intracellular enzymes and extracellular enzymes, and was achieved through four proposed biotransformation pathways with the occurrences of demethylation, hydroxylation, nitration, formylation, oxidation, bond cleavage and ring opening. Strain GZWM139 responded to the SMX removal process by altering properties of cell membrane and motivating activities of xenobiotic-metabolizing enzymes and antioxidant system. Genomic analysis proved the existence of functional genes relevant to the SMX removal in strain GZWM139 and provided echoing genetic insights for revealing the SMX removal mechanism. Strain GZWM139 performed efficient detoxification of SMX and accomplished simultaneous removal of SMX and nitrogen in both mariculture sewage and domestic sewage. The findings are significant to the effective elimination of SMX pollution and comprehensive cognitions on metabolic mechanisms of SMX removal.


Assuntos
Esgotos , Sulfametoxazol , Antibacterianos/metabolismo , Antioxidantes/metabolismo , Biotransformação , Nitrogênio , Sulfametoxazol/metabolismo , Xenobióticos
2.
Food Microbiol ; 109: 104148, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36309447

RESUMO

Despite increasing interest to investigate horizontal gene transfer as a leading cause of antibiotic resistance spread, the resistome is not only influenced by the influx and efflux of genes in different environments. Rather, the expression of existing genes under different stress conditions requires special attention. This study determined whether pre-adapting Lactiplantibacillus pentosus strains, isolated from Aloreña green table olives, to vegetable-based edible oils influence their phenotypic and genotypic responses to antibiotics. This has significant diet, food matrix, gut health, and food safety concerns. Pre-adapting L. pentosus strains to oils significantly changed their susceptibility profile to antibiotics. However, results generally differed among the three strains; although changes in the Minimum Inhibitory Concentration (MIC) of antibiotics occurred, it depended on the L. pentosus strain and the oil used for adaptation. The pre-adaptation of L. pentosus strains with olive, sunflower, argan and linseed oils induced gene expressions (e.g., rpsL, recA and uvrB) in several stress responses. Thus, to analyze this fact in-depth, transcriptional changes were reported in the selected potential probiotic L. pentosus CF2-10 adapted with olive or sunflower, rerouting its metabolic pathways to export toxic molecules through efflux pumps and ABC transporters. Pre-adaptation of some lactobacilli with olive or sunflower oils may represent a novel approach for manufacturing probiotic products with improved stability, functionality and robustness.


Assuntos
Lactobacillus pentosus , Olea , Probióticos , Microbiologia de Alimentos , Fermentação , Lactobacillus pentosus/metabolismo , Probióticos/metabolismo , Antibacterianos/farmacologia , Antibacterianos/metabolismo , Óleos
3.
Sci Total Environ ; 857(Pt 3): 159536, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36280067

RESUMO

Combined veterinary antibiotics (CVAs) belonging to different antibiotics classes could cause exacerbated impacts on the anaerobic digestion (AD) process of swine manure. Four different antibiotics "two tetracyclines: tetracycline (TC) and oxytetracycline (OTC), one fluoroquinolones: norfloxacin (Norf), and one sulfonamides: sulfadiazine (SDZ)" were combined to evaluate their removal performances and its inhibition effects on AD. Results indicated that CVAs removal decreased from 84.3 to 63.7 %, with an increase in the initial concentration from 12.5 to 50 mg L-1, where the removal of CVAs occurring in the order OTC > TC > Norf > SDZ. An average of 9.5, 7.5, 9.5, and 32.1 % of the spiked TC, OTC, SDZ, and Norf were remained in the sludge, respectively. With 50 mg L-1 of CVAs, a competitive adsorption phenomenon was found to have a notable impact on biodegradation microorganisms' activity leading a 73.1 % decrease in CH4 production. CVAs caused a temporal inhibition to the acidogenic activity followed by partial inhibition to methanogenic by 66.8 %, and IC50 was 38.5 mg L-1. Moreover, CVAs resulted in acetate accumulation, while 26 % and 48 % lower in TS and COD removal, respectively, were observed. A significant reduction in the relative abundance of bacteria and archaeal genera was also mentioned. The findings of this research would provide a more in-depth understanding of AD's performance in treating swine manure contaminated with combined antibiotics.


Assuntos
Compostos Heterocíclicos , Oxitetraciclina , Suínos , Animais , Oxitetraciclina/metabolismo , Esterco/microbiologia , Tetraciclina , Sulfadiazina , Norfloxacino , Anaerobiose , Antibacterianos/metabolismo , Tetraciclinas
4.
Environ Monit Assess ; 195(1): 75, 2022 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-36334179

RESUMO

Quorum sensing (QS) is a system of bacteria in which cells communicate with each other; it is linked to cell density in the microbiome. The high-density colony population can provide enough small molecular signals to enable a range of cellular activities, gene expression, pathogenicity, and antibiotic resistance that cause damage to the hosts. QS is the basis of chronic illnesses in human due to microbial sporulation, expression of virulence factors, biofilm formation, secretion of enzymes, or production of membrane vesicles. The transfer of antimicrobial resistance gene (ARG) among antibiotic resistance bacteria is a major public health concern. QS-mediated biofilm is a hub for ARG horizontal gene transfer. To develop innovative approach to prevent microbial pathogenesis, it is essential to understand the role of QS especially in response to environmental stressors such as exposure to antibiotics. This review provides the latest knowledge on the relationship of QS and pathogenicity and explore the novel approach to control QS via quorum quenching (QQ) using QS inhibitors (QSIs) and QQ enzymes. The state-of-the art knowledge on the role of QS and the potential of using QQ will help to overcome the threats of rapidly emerging bacterial pathogenesis.


Assuntos
Anti-Infecciosos , Percepção de Quorum , Humanos , Percepção de Quorum/fisiologia , Virulência , Monitoramento Ambiental , Bactérias , Biofilmes , Antibacterianos/toxicidade , Antibacterianos/metabolismo , Anti-Infecciosos/metabolismo
5.
World J Microbiol Biotechnol ; 39(1): 3, 2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36344903

RESUMO

Due to increasing antibiotic resistance, targeting bacterial virulence factors is now gaining further interest as an alternative strategy to develop novel classes of anti-infective agents. The critical role of α-hemolysin (Hla), an indispensable virulence determinant, in the pathogenicity of Staphylococcus aureus renders this virulence factor an appealing target for effective therapeutic applications. Herein, we identified a natural compound schisandraone, as an effective Hla inhibitor, which could inhibit Hla production and thus hemolytic activity in a dose-dependent manner without affecting the growth of S. aureus. We also found that the addition of schisandrone could down-regulate the transcriptional levels of the hla, agrA and RNAIII and significantly alleviated Hla-mediated injury of A549 cells co-cultured with S. aureus. In vivo studies further suggested that schisandrone combined with antibiotic ceftiofur exhibited a significant therapeutic effect on S. aureus infection. These findings revealed the role of schisandrone in inhibiting the activity of Hla and we believe that it is a promising anti-virulence candidate to combat MRSA pneumonia.


Assuntos
Toxinas Bacterianas , Staphylococcus aureus Resistente à Meticilina , Pneumonia Estafilocócica , Infecções Estafilocócicas , Humanos , Proteínas Hemolisinas/metabolismo , Staphylococcus aureus , Toxinas Bacterianas/metabolismo , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Antibacterianos/farmacologia , Antibacterianos/metabolismo , Fatores de Virulência/metabolismo
6.
ACS Appl Mater Interfaces ; 14(46): 51763-51775, 2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36373472

RESUMO

Postcataract endophthalmitis (PCE), a devastating complication following cataract surgeries, is one of the most crucial diseases causing irreversible eye blindness. Pseudomonas aeruginosa (PA), a multiple-drug-resistance (MDR) pathogen, always leads to uncontrolled infection and severe inflammation in PCE that can be difficult to treat by antibiotics. Therefore, it is urgent to develop new feasible strategies composed of both antibacterial and anti-inflammatory capabilities. Here, we report a multifunctional non-antibiotic nanoplatform (Ga-mSiO2-BFN) comprised of clinically approved gallium, mesoporous silica, and bromfenac (BFN) as a co-modified release system to simultaneously eradicate MDR-PA infection and cure inflammation for PCE. The released gallium ions can disrupt bacterial iron metabolism. Meanwhile, the simultaneously released BFN can suppresses the inflammation both postoperation and postinfection of PCE. In the PCE rabbit model, the slit-lamp dispersion and retro-illumination micrograph, ophthalmic clinical grading, and etiological histopathology analysis demonstrated that Ga-mSiO2-BFN could eradicate the MDR infection and alleviate the secondary inflammation from MDR-PA infection. Moreover, both cellular biocompatibility and in vivo animal model application verified the biocompatibility. A potential antibacterial mechanism implicated in the antibacterial action was demonstrated by comprehensive assays of iron antagonism evolutionary curve, colony autofluorescence, polymerase chain reaction, and electron microscopy, showing a repressing siderophore peptide pyoverdine, pyoverdine synthetase D, and interfering with bacterial DNA synthesis. All composites of our nanoplatform were FDA approved, making the Ga-mSiO2-BFN as a potentially promising therapeutic approach for treating MDR-PA in PCE accompanying satisfactory prognosis and prospects for clinical translations.


Assuntos
Catarata , Endoftalmite , Gálio , Infecções por Pseudomonas , Animais , Coelhos , Pseudomonas aeruginosa/metabolismo , Gálio/farmacologia , Gálio/uso terapêutico , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Endoftalmite/tratamento farmacológico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Antibacterianos/metabolismo , Bactérias/metabolismo , Ferro/metabolismo , Inflamação/tratamento farmacológico , Catarata/tratamento farmacológico
7.
BMC Vet Res ; 18(1): 410, 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36411417

RESUMO

BACKGROUND: The holin-endolysin lysis system plays an essential role in the phage life cycle. Endolysins are promising alternatives to antibiotics, and have been successfully used against Gram-positive bacteria. However, a few endolysins can externally lyse Gram-negative bacteria, due to the inaccessible peptidoglycan layer covered by the envelope. RESULTS: This study investigated the lysis system of a new Siphoviridae bacteriophage vB_Sal-S-S10 (S10), which, that was isolated from broiler farms, was found to be able to infect 51.4% (37/72) of tested S. enteritidis strains. Phage S10 genome had a classic holin-endolysin lysis system, except that one holin and one endolysin gene were functionally annotated. The orf 22 adjacent to the lysis cassette was identified as a new endolysin gene. Antibacterial activity assays showed that holin had an intracellular penetrating activity against S. enteritidis 35; both endolysins acted on the cell envelope of S. enteritidis 35 and showed a natural extracellular antibacterial activity, leading to a ~ 1 log titer decrease in 30 min. Protein characterization of lysin1 and lysin2 revealed that the majority of the N-terminus and the C-terminus were hydrophobic amino acids or positively charged. CONCLUSION: In this study, a new Salmonella phage vB_Sal-S-S10 (S10) was characterized and showed an ideal development prospect. Phage S10 has a classic holin-endolysin lysis system, carrying an overlapping holin-lysin gene and a novel lysin gene. Both endolysins coded by lysin genes could externally lyse S. enteritidis. The natural extracellular antibacterial character of endolysins would provide necessary information for the development of engineering endolysin as the antibiotic alternative against the infection with multidrug-resistant gram-negative bacteria.


Assuntos
Bacteriófagos , Animais , Bacteriófagos/metabolismo , Salmonella enteritidis , Galinhas , Antibacterianos/farmacologia , Antibacterianos/metabolismo
8.
Biomolecules ; 12(11)2022 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-36358894

RESUMO

Antibiotic resistance in bacteria has remained a serious public health concern, resulting in substantial deaths and morbidity each year. Factors such as mutation and abuse of currently available antibiotics have contributed to the bulk of the menace. Hence, the introduction and implementation of new therapeutic strategies are imperative. Of these strategies, data supporting the role of reactive oxygen species (ROS) in bacterial lethality are intriguing, with several antimicrobials, including antibiotics such as fluoroquinolones, ß-lactams, and aminoglycosides, as well as natural plant compounds, being remarkably implicated. Following treatment with ROS-inducing antimicrobials, ROS such as O2•-, •OH, and H2O2 generated in bacteria, which the organism is unable to detoxify, damage cellular macromolecules such as proteins, lipids, and nucleic acids and results in cell death. Despite the unique mechanism of action of ROS-inducing antibacterials and significant studies on ROS-mediated means of bacterial killing, the field remains a topical one, with contradicting viewpoints that require frequent review. Here, we appraised the antibacterial agents (antibiotics, natural and synthetic compounds) implicated in ROS generation and the safety concerns associated with their usage. Further, background information on the sources and types of ROS in bacteria, the mechanism of bacterial lethality via oxidative stress, as well as viewpoints on the ROS hypothesis undermining and solidifying this concept are discussed.


Assuntos
Anti-Infecciosos , Peróxido de Hidrogênio , Espécies Reativas de Oxigênio/metabolismo , Peróxido de Hidrogênio/metabolismo , Bactérias/metabolismo , Antibacterianos/farmacologia , Antibacterianos/metabolismo , Oxirredução , Estresse Oxidativo , Anti-Infecciosos/metabolismo
9.
ACS Infect Dis ; 8(11): 2242-2252, 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36318734

RESUMO

In the hunt for new antibiotics with activity against Gram-negative pathogens, the outer membrane ß-barrel assembly machine (BAM) complex has become an increasingly interesting target. The recently reported BAM complex inhibitor, MRL-494, was discovered via a screening campaign for molecules that target the outer membrane. Notably, MRL-494 was reported to be an unintended byproduct generated during the synthesis of an unrelated compound, and as such no synthesis of the compound was disclosed. We here present a convenient and reliable route for the synthesis of MRL-494 that scales well. The antibacterial activity measured for synthesized MRL-494 matches that reported in the literature. Furthermore, MRL-494 was found to exhibit potent synergistic activity with rifampicin against Gram-negative bacteria, including E. coli, K. pneumoniae, A. baumannii, and P. aeruginosa. MRL-494 was also found to cause outer membrane disruption and induction of the Rcs stress response pathway. In addition, we undertook a focused structure-activity study specifically aimed at elucidating the roles played by the two guanidine moieties contained within the structure of MRL-494.


Assuntos
Proteínas de Escherichia coli , Escherichia coli , Escherichia coli/metabolismo , Proteínas de Escherichia coli/metabolismo , Proteínas da Membrana Bacteriana Externa/metabolismo , Antibacterianos/farmacologia , Antibacterianos/metabolismo
10.
Biochem Biophys Res Commun ; 636(Pt 2): 10-17, 2022 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-36343485

RESUMO

Acinetobacter baumannii forms robust biofilms, which aid protection against antimicrobials and account for adaptation in hospital settings. Biofilm formation by A. baumannii has worsens the scenario of drug resistance. Therefore, new strategies are required to tackle biofilm-forming multidrug-resistant A. baumannii. The present study investigated compounds with antimicrobials and antibiofilm properties against A. baumannii. Different antimicrobials were selected from available reports. Initially, comparative antimicrobial activity against A. baumannii isolates was assessed. Most potent antimicrobial compounds were further analyzed for time-kill kinetics, biofilm inhibition, and exopolysaccharide (EPS) reduction in their presence and absence. The antibiofilm potentials were also confirmed with SEM analysis. The relative gene expression of the csuE gene and molecular docking was carried out to investigate the molecular mechanism of mature biofilm disruption. The results demonstrated eugenol and geraniol as the most potent inhibitors with MICs of 6.08 mM and 3.24 mM, respectively, with the potential to significantly inhibit growth and EPS production. Complete inhibition of A. baumannii mature biofilms was observed with a maximum of 60.89 mM and 129.6 mM concentrations of eugenol and geraniol, respectively. The SEM analysis and lower expression of the csuE gene showed the effectiveness of potent antibiofilm agents. In-silico docking showed efficient binding of eugenol and geraniol with the csuE protein of archaic pilus. The findings of molecular docking concordant the assumption that these molecules may prevent the assembly of mature pilus, which results in abolished biofilms. In conclusion, the antibiofilm virtues of eugenol and geraniol were elucidated to be used in the future to control the persistence of biofilm-forming drug-resistant A. baumannii.


Assuntos
Acinetobacter baumannii , Acinetobacter baumannii/genética , Eugenol/farmacologia , Simulação de Acoplamento Molecular , Biofilmes , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Antibacterianos/metabolismo , Farmacorresistência Bacteriana Múltipla/genética
11.
Elife ; 112022 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-36350124

RESUMO

Bacteria of the order Corynebacteriales including pathogens such as Mycobacterium tuberculosis and Corynebacterium diphtheriae are characterized by their complex, multi-layered envelope. In addition to a peptidoglycan layer, these organisms possess an additional polysaccharide layer made of arabinogalactan and an outer membrane layer composed predominantly of long-chain fatty acids called mycolic acids. This so-called mycolata envelope structure is both a potent barrier against antibiotic entry into cells and a target of several antibacterial therapeutics. A better understanding of the mechanisms underlying mycolata envelope assembly therefore promises to reveal new ways of disrupting this unique structure for the development of antibiotics and antibiotic potentiators. Because they engage with receptors on the cell surface during infection, bacteriophages have long been used as tools to uncover important aspects of host envelope assembly. However, surprisingly little is known about the interactions between Corynebacteriales phages and their hosts. We therefore made use of the phages Cog and CL31 that infect Corynebacterium glutamicum (Cglu), a model member of the Corynebacteriales, to discover host factors important for phage infection. A high-density transposon library of Cglu was challenged with these phages followed by transposon sequencing to identify resistance loci. The analysis identified an important role for mycomembrane proteins in phage infection as well as components of the arabinogalactan and mycolic acid synthesis pathways. Importantly, the approach also implicated a new gene (cgp_0396) in the process of arabinogalactan modification and identified a conserved new factor (AhfA, Cpg_0475) required for mycolic acid synthesis in Cglu.


Assuntos
Bacteriófagos , Corynebacterium glutamicum , Ácidos Micólicos/metabolismo , Bacteriófagos/genética , Bacteriófagos/metabolismo , Parede Celular/metabolismo , Corynebacterium glutamicum/genética , Corynebacterium glutamicum/metabolismo , Antibacterianos/farmacologia , Antibacterianos/metabolismo
12.
Int J Mol Sci ; 23(21)2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36361855

RESUMO

Proteus mirabilis is a common cause of catheter-associated urinary tract infections (CAUTIs). In this study, we verified the effectiveness of amikacin or gentamicin and ascorbic acid (AA) co-therapy in eliminating uropathogenic cells, as well as searched for the molecular basis of AA activity by applying chromatographic and fluorescent techniques. Under simulated physiological conditions, a combined activity of the antibiotic and AA supported the growth (threefold) of the P. mirabilis C12 strain, but reduced catheter colonization (≤30%) in comparison to the drug monotherapy. Slight modifications in the phospholipid and fatty acid profiles, as well as limited (≤62%) 2',7'-dichlorofluorescein fluorescence, corresponding to the hydroxyl radical level, allowed for the exclusion of the hypothesis that the anti-biofilm effect of AA was related to membrane perturbations of the C12 strain. However, the reduced (≤20%) fluorescence intensity of propidium iodide, as a result of a decrease in membrane permeability, may be evidence of P. mirabilis cell defense against AA activity. Quantitative analyses of ascorbic acid over time with a simultaneous measurement of the pH values proved that AA can be an effective urine acidifier, provided that it is devoid of the presence of urease-positive cells. Therefore, it could be useful in a prevention of recurrent CAUTIs, rather than in their treatment.


Assuntos
Infecções por Proteus , Infecções Urinárias , Humanos , Proteus mirabilis/metabolismo , Aminoglicosídeos/metabolismo , Ácido Ascórbico/farmacologia , Ácido Ascórbico/metabolismo , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/prevenção & controle , Infecções Urinárias/patologia , Biofilmes , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Antibacterianos/metabolismo , Cateteres , Infecções por Proteus/tratamento farmacológico
13.
Int J Mol Sci ; 23(21)2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36361877

RESUMO

The development of bacterial resistance to antibiotics is an increasing public health issue that worsens with the formation of biofilms. Quorum sensing (QS) orchestrates the bacterial virulence and controls the formation of biofilm. Targeting bacterial virulence is promising approach to overcome the resistance increment to antibiotics. In a previous detailed in silico study, the anti-QS activities of twenty-two ß-adrenoreceptor blockers were screened supposing atenolol as a promising candidate. The current study aims to evaluate the anti-QS, anti-biofilm and anti-virulence activities of the ß-adrenoreceptor blocker atenolol against Gram-negative bacteria Serratia marcescens, Pseudomonas aeruginosa, and Proteus mirabilis. An in silico study was conducted to evaluate the binding affinity of atenolol to S. marcescens SmaR QS receptor, P. aeruginosa QscR QS receptor, and P. mirabilis MrpH adhesin. The atenolol anti-virulence activity was evaluated against the tested strains in vitro and in vivo. The present finding shows considerable ability of atenolol to compete with QS proteins and significantly downregulated the expression of QS- and virulence-encoding genes. Atenolol showed significant reduction in the tested bacterial biofilm formation, virulence enzyme production, and motility. Furthermore, atenolol significantly diminished the bacterial capacity for killing and protected mice. In conclusion, atenolol has potential anti-QS and anti-virulence activities against S. marcescens, P. aeruginosa, and P. mirabilis and can be used as an adjuvant in treatment of aggressive bacterial infections.


Assuntos
Atenolol , Fatores de Virulência , Camundongos , Animais , Atenolol/farmacologia , Atenolol/metabolismo , Fatores de Virulência/genética , Percepção de Quorum , Biofilmes , Bactérias Gram-Negativas , Pseudomonas aeruginosa , Serratia marcescens/metabolismo , Antibacterianos/farmacologia , Antibacterianos/metabolismo , Proteus mirabilis/metabolismo , Proteínas de Bactérias/metabolismo
14.
Int J Mol Sci ; 23(21)2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36362282

RESUMO

Pseudomonas aeruginosa is an opportunistic pathogen causing several chronic infections resistant to currently available antibiotics. Its pathogenicity is related to the production of different virulence factors such as biofilm and protease secretion. Pseudomonas communities can persist in biofilms that protect bacterial cells from antibiotics. Hence, there is a need for innovative approaches that are able to counteract these virulence factors, which play a pivotal role, especially in chronic infections. In this context, antimicrobial peptides are emerging drugs showing a broad spectrum of antibacterial activity. Here, we tested the anti-virulence activity of a chionodracine-derived peptide (KHS-Cnd) on five P. aeruginosa clinical isolates from cystic fibrosis patients. We demonstrated that KHS-Cnd impaired biofilm development and caused biofilm disaggregation without affecting bacterial viability in nearly all of the tested strains. Ultrastructural morphological analysis showed that the effect of KHS-Cnd on biofilm could be related to a different compactness of the matrix. KHS-Cnd was also able to reduce adhesion to pulmonary cell lines and to impair the invasion of host cells by P. aeruginosa. A cytotoxic effect of KHS-Cnd was observed only at the highest tested concentration. This study highlights the potential of KHS-Cnd as an anti-biofilm and anti-virulence molecule against P. aeruginosa clinical strains.


Assuntos
Fibrose Cística , Infecções por Pseudomonas , Humanos , Pseudomonas aeruginosa , Virulência , Fibrose Cística/tratamento farmacológico , Fibrose Cística/microbiologia , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Biofilmes , Fatores de Virulência/metabolismo , Antibacterianos/farmacologia , Antibacterianos/metabolismo , Peptídeos/farmacologia , Peptídeos/metabolismo , Testes de Sensibilidade Microbiana
15.
Appl Microbiol Biotechnol ; 106(23): 7917-7931, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36350402

RESUMO

Low-protein (LP) feeds are used in the poultry industry to combat the increasing consumption of protein resources and reduce environmental pollution caused by excessive nitrogen excretion. Dietary supplementation of protease or Clostridium butyricum increases the growth performance of broilers; however, it is unclear whether they counteract the negative effects of LP diets. The effects of protease and C. butyricum on growth performance, intestinal morphology, anti-oxidant capacity, anti-inflammatory response, and microbial community of broilers have not been studied extensively. Here, 450 healthy 1-day-old Cobb500 broilers were allocated to five groups, according to different diets: basal diet (Control); LP diet (LP; 2% less crude protein than the control); LP diet + 200 g/t HuPro protease (LPH); LP diet + 1.0 × 109 CFU/t C. butyricum (LPC); and basal diet + 200 g/t oxytetracycline (Antibiotic). Supplementing both C. butyricum and protease improved the growth performance of broilers. The supplementation of HuPro protease under low-protein conditions could achieve a breeding effect similar to that of the positive control (Antibiotic). Supplementing C. butyricum could maintain intestinal barrier function, alleviate the inflammatory response, and increase ileal and cecal short-chain fatty acid concentrations. Both C. butyricum and protease altered the bacterial diversity in the cecum, increased Bacteroidetes abundance, and resulted in higher abundance of Rikenellaceae RC9 gut spp. and lower abundance of Alistipes spp. in broilers. This study demonstrates the positive effects of proteases and C. butyricum on broilers and serves as a reference for the selection of appropriate supplementation for broilers in the poultry industry. KEY POINTS: • Low-protein diet had a negative effect on growth performance of broilers. • Protease significantly reduced feed conversion rate. • Clostridium butyricum had positive effects on broilers.


Assuntos
Clostridium butyricum , Animais , Clostridium butyricum/fisiologia , Dieta com Restrição de Proteínas , Galinhas , Ração Animal/análise , Peptídeo Hidrolases/metabolismo , Dieta/veterinária , Antibacterianos/metabolismo
16.
Mar Drugs ; 20(11)2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36355025

RESUMO

To explore the application of chitosan-gentamicin conjugate (CS-GT) in inhibiting Vibrio parahaemolyticus (V. parahaemolyticus), which is an important pathogen in aquatic animals worldwide, the antimicrobial activity of CS-GT and the effects of a CS-GT dose on the intestine histopathology and intestinal flora of V. parahaemolyticus-infected shrimps were explored. The results showed that CS-GT possessed broad-spectrum antibacterial activity, with minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and half inhibitory concentration (IC50) of 20.00 ± 0.01, 75.00 ± 0.02 and 18.72 ± 3.17 µg/mL for V. parahaemolyticus, respectively. Further scanning electron microscope and cell membrane damage analyses displayed that the electrostatic interaction of CS-GT with cell membrane strengthened after CS grafted GT, resulting in leakage of nucleic acid and electrolytes of V. parahaemolyticus. On the other hand, histopathology investigation indicated that high (100 mg/kg) and medium (50 mg/kg) doses of CS-GT could alleviate the injury of a shrimp's intestine caused by V. parahaemolyticus. Further 16S rRNA gene sequencing analysis found high and medium dose of CS-GT could effectively inhabit V. parahaemolyticus invasion and reduce intestinal dysfunction. In conclusion, CS-GT possesses good antibacterial activity and could protect shrimps from pathogenic bacteria infection.


Assuntos
Quitosana , Microbioma Gastrointestinal , Penaeidae , Vibrio parahaemolyticus , Animais , Quitosana/farmacologia , Quitosana/metabolismo , Gentamicinas/farmacologia , RNA Ribossômico 16S/metabolismo , Penaeidae/genética , Antibacterianos/farmacologia , Antibacterianos/metabolismo
17.
J Microbiol Biotechnol ; 32(11): 1390-1395, 2022 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36437519

RESUMO

Acne is a chronic inflammatory disease of the sebaceous gland attached to the hair follicles. Cutibacterium acnes is a major cause of inflammation caused by acne. It is well known that C. acnes secretes a lipolytic enzyme to break down lipids in sebum, and free fatty acids produced at this time accelerate the inflammatory reaction. There are several drugs used to treat acne; however, each one has various side effects. According to previous studies, sulforaphene (SFEN) has several functions associated with lipid metabolism, brain function, and antibacterial and anti-inflammatory activities. In this study, we examined the effects of SFEN on bacterial growth and inflammatory cytokine production induced by C. acnes. The results revealed that SFEN reduced the growth of C. acnes and inhibited proinflammatory cytokines in C. acnes-treated HaCaT keratinocytes through inhibiting NF-κB-related pathways. In addition, SFEN regulated the expression level of IL-1α, a representative pro-inflammatory cytokine expressed in co-cultured HaCaT keratinocytes and THP-1 monocytes induced by C. acnes. In conclusion, SFEN showed antibacterial activity against C. acnes and controlled the inflammatory response on keratinocytes and monocytes. This finding means that SFEN has potential as both a cosmetic material for acne prevention and a pharmaceutical material for acne treatment.


Assuntos
Acne Vulgar , Propionibacterium acnes , Humanos , Inflamação/tratamento farmacológico , Acne Vulgar/tratamento farmacológico , Acne Vulgar/microbiologia , Antibacterianos/metabolismo
18.
Int J Mol Sci ; 23(22)2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36430568

RESUMO

Yersiniosis, caused by Yersinia enterocolitica, is the third most rampant zoonotic disease in Europe; the pathogen shows high antibiotic resistance. Herbs have multiple anti-microbial components that reduce microorganism resistance. Therefore, an extract of Picrorhiza kurroa (P. kurroa) was evaluated for potential antimicrobial activity. We report that the ethanolic extract of P. kurroa showed effective antimicrobial activity (zone of inhibition: 29.8 mm, Minimum inhibitory concentration (MIC): 2.45 mg/mL, minimum bactericidal concentration (MBC): 2.4 mg/mL) against Yersinia enterocolitica. Potential bioactive compounds from P. kurroa were identified using LC-MS, namely, cerberidol, annonidine A, benzyl formate, picroside-1, and furcatoside A. P. kurroa showed effective antimicrobial potential in skim milk at different pH, acidity, and water activity levels. P. kurroa affected the physiology of Yersinia enterocolitica and reduced the number of live cells. Yersinia enterocolitica, when incubated with P. kurroa extract, showed lower toxin production. Picroside-1 was isolated and showed higher antimicrobial potential in comparison to the standard antibiotic. Picroside-1 lysed the Yersinia enterocolitica cells, as observed under scanning electron microscopy. Docking revealed that picroside-1 (ligand) showed both hydrophilic and hydrophobic interactions with the dihydrofolate reductase (DHFR) protein of Yersinia enterocolitica and that DHFR is a possible drug target. The high activity and natural origin of Picroside-1 justify its potential as a possible drug candidate for Yersinia enterocolitica.


Assuntos
Anti-Infecciosos , Picrorhiza , Yersinia enterocolitica , Picrorhiza/química , Picrorhiza/metabolismo , Anti-Infecciosos/farmacologia , Antibacterianos/farmacologia , Antibacterianos/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/metabolismo
19.
Int J Mol Sci ; 23(22)2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36430829

RESUMO

The localization of lipoprotein (Lol) system is responsible for the transport of lipoproteins in the outer membrane (OM) of Vibrio parahaemolyticus. LolB catalyzes the last step in the Lol system, where lipoproteins are inserted into the OM. If the function of LolB is impeded, growth of V. parahaemolyticus is inhibited, due to lack of an intact OM barrier for protection against the external environment. Additionally, it becomes progressively harder to generate antimicrobial resistance (AMR). In this study, LolB was employed as the receptor for a high-throughput virtual screening from a natural compounds database. Compounds with higher glide score were selected for an inhibition assay against V. parahaemolyticus. It was found that procyanidin, stevioside, troxerutin and rutin had both exciting binding affinity with LolB in the micromolar range and preferable antibacterial activity in a concentration-dependent manner. The inhibition rates of 100 ppm were 87.89%, 86.2%, 91.39% and 83.71%, respectively. The bacteriostatic mechanisms of the four active compounds were explored further via fluorescence spectroscopy and molecular docking, illustrating that each molecule formed a stable complex with LolB via hydrogen bonds and pi-pi stacking interactions. Additionally, the critical sites for interaction with V. parahaemolyticus LolB, Tyr108 and Gln68, were also illustrated. This paper demonstrates the inhibition of LolB, thus, leading to antibacterial activity, and identifies LolB as a promising drug target for the first time. These compounds could be the basis for potential antibacterial agents against V. parahaemolyticus.


Assuntos
Proteínas de Escherichia coli , Proteínas Periplásmicas de Ligação , Vibrio parahaemolyticus , Proteínas de Escherichia coli/metabolismo , Proteínas Periplásmicas de Ligação/metabolismo , Proteínas da Membrana Bacteriana Externa/química , Vibrio parahaemolyticus/metabolismo , Escherichia coli/metabolismo , Simulação de Acoplamento Molecular , Chaperonas Moleculares/metabolismo , Lipoproteínas/metabolismo , Antibacterianos/farmacologia , Antibacterianos/metabolismo
20.
Int J Mol Sci ; 23(22)2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36430942

RESUMO

The overexpression of efflux pumps is one of the strategies used by bacteria to resist antibiotics and could be targeted to circumvent the antibiotic crisis. In this work, a series of trimethoxybenzoic acid derivatives previously described as antifouling compounds was explored for potential antimicrobial activity and efflux pump (EP) inhibition. First, docking studies on the acridine resistance proteins A and B coupled to the outer membrane channel TolC (AcrAB-TolC) efflux system and a homology model of the quinolone resistance protein NorA EP were performed on 11 potential bioactive trimethoxybenzoic acid and gallic acid derivatives. The synthesis of one new trimethoxybenzoic acid derivative (derivative 13) was accomplished. To investigate the potential of this series of 11 derivatives as antimicrobial agents, and in reverting drug resistance, the minimum inhibitory concentration was determined on several strains (bacteria and fungi), and synergy with antibiotics and EP inhibition were investigated. Derivative 10 showed antibacterial activity against the studied strains, derivatives 5 and 6 showed the ability to inhibit EPs in the acrA gene inactivated mutant Salmonella enterica serovar Typhimurium SL1344, and 6 also inhibited EPs in Staphylococcus aureus 272123. Structure-activity relationships highlighted trimethoxybenzoic acid as important for EP inhibitory activity. Although further studies are necessary, these results show the potential of simple trimethoxybenzoic acid derivatives as a source of feasible EP inhibitors.


Assuntos
Proteínas de Bactérias , Ácido Gálico , Ácido Gálico/farmacologia , Ácido Gálico/metabolismo , Proteínas de Bactérias/metabolismo , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Antibacterianos/metabolismo , Staphylococcus aureus/metabolismo
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