Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.781
Filtrar
1.
Mar Drugs ; 23(1)2025 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-39852545

RESUMO

The rise in multidrug-resistant (MDR) bacteria has prompted extensive research into antibacterial compounds, as these resistant strains compromise current treatments. This resistance leads to prolonged hospitalization, increased mortality rates, and higher healthcare costs. To address this challenge, the pharmaceutical industry is increasingly exploring natural products, particularly those of marine origin, as promising candidates for antimicrobial drugs. Marine sponges, in particular, are of interest because of their production of secondary metabolites (SM), which serve as chemical defenses against predators and pathogens. These metabolites exhibit a wide range of therapeutic properties, including antibacterial activity. This systematic review examines recent advancements in identifying new sponge-derived compounds with antimicrobial activity, specifically targeting Pseudomonas aeruginosa, a prevalent Gram-negative pathogen with the highest incidence rates in clinical settings. The selection criteria focused on antimicrobial compounds with reported Minimum Inhibitory Concentration (MIC) values. The identified SM include alkaloids, sesterterpenoids, nitrogenous diterpene, and bromotyrosine-derived derivatives. The structural features of the active compounds selected in this review may provide a foundational framework for developing new, highly bioactive antimicrobial agents.


Assuntos
Antibacterianos , Produtos Biológicos , Poríferos , Antibacterianos/farmacologia , Antibacterianos/química , Animais , Produtos Biológicos/farmacologia , Produtos Biológicos/química , Testes de Sensibilidade Microbiana , Humanos , Pseudomonas aeruginosa/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Organismos Aquáticos , Alcaloides/farmacologia , Alcaloides/química
2.
World J Microbiol Biotechnol ; 41(2): 32, 2025 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-39794611

RESUMO

Bacteria coordinate gene expression in a cell density-dependent manner in a communication process called quorum sensing (QS). The expression of virulence factors, biofilm formation and enzyme production are QS-regulated phenotypes that can interfere in human health. Due to this importance, there is great interest in inhibiting QS, comprising an anti-virulence strategy. This work aimed to evaluate the effect of selected phenolic compounds on the inhibition of QS-regulated phenotypes in Pseudomonas aeruginosa PAO1, using concentrations that do not interfere in bacterial growth. This is one of the main premises for studying the effect of compounds on QS. Firstly, an in-silico study with the LasR and RhlR proteins of P. aeruginosa by molecular docking of 82 phenolic compounds was performed. Then, a screening with 13 selected phenolic compounds was performed, using biosensor strains P. aeruginosa lasB-gfp and P. aeruginosa rhlA-gfp, which emit fluorescence when the QS system is activated. From this assay, eight compounds were selected and evaluated for inhibition of pyocyanin, rhamnolipids, proteases, elastase, and motility. The compounds variably inhibited the evaluated virulence factors. The greatest inhibitions were observed for swarming motility, achieving inhibition rates of up to 50% for baicalein (500 µM) and curcumin (50 µM). Notably, curcumin showed satisfactory inhibition for all phenotypes even at lower concentrations (12.5 to 50 µM) compared to the other compounds (125 to 500 µM). Four compounds - rosmarinic acid, baicalein, curcumin, and resveratrol - were finally tested against biofilm formation observed by optical microscopy. This study demonstrated that phenolic compounds exhibit strong in silico binding to P. aeruginosa LasR and RhlR proteins and variably inhibit QS-regulated phenotypes in vitro. Although no biofilm inhibition was observed, future studies combining compounds and exploring molecular mechanisms are recommended. These findings highlight the biotechnological potential of phenolic compounds for future applications in the food, clinical, and pharmaceutical fields.


Assuntos
Antibacterianos , Proteínas de Bactérias , Biofilmes , Simulação de Acoplamento Molecular , Fenóis , Pseudomonas aeruginosa , Percepção de Quorum , Transativadores , Fatores de Virulência , Percepção de Quorum/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/fisiologia , Fatores de Virulência/metabolismo , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Fenóis/farmacologia , Fenóis/química , Antibacterianos/farmacologia , Antibacterianos/química , Virulência/efeitos dos fármacos , Transativadores/metabolismo , Transativadores/genética , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Piocianina/metabolismo , Glicolipídeos/farmacologia , Glicolipídeos/química , Glicolipídeos/metabolismo , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos
3.
Med Sci (Basel) ; 13(1)2025 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-39846701

RESUMO

BACKGROUND/OBJECTIVES: Pseudomonas aeruginosa is a clinically significant opportunistic pathogen, renowned for its ability to acquire and develop diverse mechanisms of antibiotic resistance. This study examines the resistance, virulence, and regulatory mechanisms in extensively drug-resistant clinical strains of P. aeruginosa. METHODS: Antibiotic susceptibility was assessed using the Minimum Inhibitory Concentration (MIC) method, and whole-genome sequencing (WGS) was performed on the Illumina NovaSeq platform. RESULTS: The analysis demonstrated a higher prevalence of virulence genes compared to resistance and regulatory genes. Key virulence factors identified included secretion systems, motility, adhesion, and biofilm formation. Resistance mechanisms observed comprised efflux pumps and beta-lactamases, while regulatory systems involved two-component systems, transcriptional regulators, and sigma factors. Additionally, phenotypic profiles were found to correlate with resistance genes identified through genotypic analysis. CONCLUSIONS: This study underscores the significant resistance and virulence of the clinical P. aeruginosa strains analyzed, highlighting the urgent need for alternative strategies to address infections caused by extensively drug-resistant bacteria.


Assuntos
Antibacterianos , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa , Fatores de Virulência , Sequenciamento Completo do Genoma , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/patogenicidade , Virulência/genética , Fatores de Virulência/genética , Humanos , Antibacterianos/farmacologia , Infecções por Pseudomonas/microbiologia , Genoma Bacteriano , Farmacorresistência Bacteriana Múltipla/genética , Biofilmes , Farmacorresistência Bacteriana/genética
4.
NPJ Biofilms Microbiomes ; 11(1): 14, 2025 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-39805827

RESUMO

Biofilms are critical in the persistence of Pseudomonas aeruginosa infections, particularly in cystic fibrosis patients. This study explores the adaptive mechanisms behind the phenotypic switching between Small Colony Variants (SCVs) and revertant states in P. aeruginosa biofilms, emphasizing hypermutability due to Mismatch Repair System (MRS) deficiencies. Through experimental evolution and whole-genome sequencing, we show that both wild-type and mutator strains undergo parallel evolution by accumulating compensatory mutations in factors regulating intracellular c-di-GMP levels, particularly in the Wsp and Yfi systems. While wild-type strains face genetic constraints, mutator strains bypass these by accessing alternative genetic pathways regulating c-di-GMP and biofilm formation. This increased genetic accessibility, driven by higher mutation rates and specific mutational biases, supports sustained cycles of SCV conversion and reversion. Our findings underscore the crucial role of hypermutability in P. aeruginosa adaptation, with significant implications for managing persistent infections in clinical settings.


Assuntos
Biofilmes , GMP Cíclico , Mutação , Fenótipo , Pseudomonas aeruginosa , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/fisiologia , Biofilmes/crescimento & desenvolvimento , GMP Cíclico/análogos & derivados , GMP Cíclico/metabolismo , Sequenciamento Completo do Genoma , Regulação Bacteriana da Expressão Gênica , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Adaptação Fisiológica/genética , Reparo de Erro de Pareamento de DNA , Humanos
5.
Commun Biol ; 8(1): 13, 2025 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-39762450

RESUMO

Pseudomonas aeruginosa is an emergent threat due to the antimicrobial resistance crisis. Bacteriophages (phages) are promising agents for phage therapy approaches against P. aeruginosa. It has been proposed that metazoans harbor phages on their mucosal surfaces, and this could be exploited for the rational design of prophylactic phage therapy. The goal of this study was to evaluate the potential of phage-mucus interaction to prevent infections caused by P. aeruginosa. We isolated two phages capable of infecting P. aeruginosa. Both are similar in morphology and closely related genetically. However, phage VAC3 is more efficient in replicating in mucin-exposed P. aeruginosa in vitro and is preferentially held in the respiratory tract of C57BL/6 mice. Pre-treatment with VAC3 phage protects mice from a lethal dose of P. aeruginosa while VAC1 does not. This shows that phages adapted to mucosal conditions have potential to be applied as prophylactic measures against an ESKAPE pathogen.


Assuntos
Camundongos Endogâmicos C57BL , Terapia por Fagos , Infecções por Pseudomonas , Pseudomonas aeruginosa , Animais , Pseudomonas aeruginosa/virologia , Infecções por Pseudomonas/prevenção & controle , Infecções por Pseudomonas/microbiologia , Infecções por Pseudomonas/terapia , Camundongos , Fagos de Pseudomonas/fisiologia , Bacteriófagos/fisiologia , Feminino , Mucosa/virologia , Mucosa/microbiologia
6.
J Med Microbiol ; 74(1)2025 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-39868561

RESUMO

Introduction. In critically ill patients, the occurrence of multidrug-resistant Pseudomonas aeruginosa infection is a significant concern, given its ability to acquire multidrug-resistant, form biofilms and secrete toxic effectors.Hypothesis or Gap Statement. In Brazil, limited data are available regarding the prevalence of dissemination, and the impact of the type III secretion system (T3SS) on toxin production and biofilm formation in clinical isolates of P. aeruginosa.Aim. This study investigates the dissemination of virulent P. aeruginosa harbouring the bla KPC-2 and bla PDC-5 genes, the presence of T3SS genes and their biofilm-forming capability.Methodology. A total of 128 non-duplicate clinical isolates of carbapenem-resistant P. aeruginosa (CRPA) from different sources collected from eight hospitals were examined. Detection was performed by PCR of the T3SS genes (exoU, exoT, exoS and exoY), carbapenemases (bla KPC, bla GIM and bla NDM) and beta-lactamase gene (bla PDC). PFGE and phenotypic biofilm production (initial adhesion assay and biofilm cell concentration) were performed.Results. We found exoT+ (86%) to be the most frequent genotypic variant, followed by exoY+ (61%). Notably, a substantial proportion of isolates exhibited the simultaneous presence of exoU+ and exoS+ genes, along with a high prevalence of bla KPC-2 + (64%) and bla PDC-5 + (64%) among the disseminated clones in the evaluated region. Additionally, 78% of the isolates demonstrated biofilm-forming capability, and two distinct clonal profiles were identified and disseminated both intra- and inter-hospital. Also, it was revealed that the exoU genotype was significantly more frequent among multidrug-resistant strains.Conclusion. These findings underscore the ability of multiple virulent and biofilm-producing clones of CRPA to propagate effectively.


Assuntos
Proteínas de Bactérias , Biofilmes , Infecções por Pseudomonas , Pseudomonas aeruginosa , Sistemas de Secreção Tipo III , beta-Lactamases , Biofilmes/crescimento & desenvolvimento , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/isolamento & purificação , Pseudomonas aeruginosa/patogenicidade , Pseudomonas aeruginosa/fisiologia , beta-Lactamases/genética , beta-Lactamases/metabolismo , Humanos , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Sistemas de Secreção Tipo III/genética , Sistemas de Secreção Tipo III/metabolismo , Infecções por Pseudomonas/microbiologia , Brasil , Hospitais , Farmacorresistência Bacteriana Múltipla/genética , Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Virulência/genética , Genótipo
7.
PLoS One ; 19(12): e0312783, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39739718

RESUMO

Multidrug resistance in Pseudomonas aeruginosa, a high-priority pathogen per the World Health Organization, poses a global threat due to carbapenem resistance and limited antibiotic treatments. Using the bioinformatic tools CRISPRCasFinder, CRISPRCasTyper, CRISPRloci, and CRISPRImmunity, we analyzed the genome of P. aeruginosa PAO1 and revealed an orphan CRISPR system, suggesting it may be a remnant of a type IV system due to the presence of the DinG protein. This system comprises two CRISPR arrays and noteworthy DinG and Cas3 proteins, supporting recent evidence about the association between type IV and I CRISPR systems. Additionally, we demonstrated a co-evolutionary relationship between the orphan CRISPR system in P. aeruginosa PAO1 and the mobile genetic element and prophages identified. One self-targeting spacer was identified, often associated with bacterial evolution and autoimmunity, and no Acr proteins. This research opens avenues for studying how these CRISPR arrays regulate pathogenicity and for developing alternative strategies using its endogenous orphan CRISPR system against carbapenem-resistant P. aeruginosa strains.


Assuntos
Sistemas CRISPR-Cas , Pseudomonas aeruginosa , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/efeitos dos fármacos , Genoma Bacteriano , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas/genética
8.
Molecules ; 29(23)2024 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-39683715

RESUMO

Four mononuclear bioefficient zinc coordination complexes [Zn(NN)3](ClO4)2 (A-D) involving chiral bidentate Schiff base ligands have been synthesized and characterized by IR, 1H, and 13C NMR spectroscopy and mass spectrometry. X-ray crystal structures of three of the zinc complexes revealed that the zinc metal ion is hexacoordinated, exhibiting a distorted octahedral geometry where both the nitrogen atoms (NN = pyridyl and imine) of imines are coordinated to the central zinc ion. The isolated zinc complexes were evaluated for their antimicrobial activity in vitro against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus, displaying varying levels of growth inhibition. An acute toxicity test conducted using Artemia salina and Swiss albino mice showed that the zinc complexes A-D were non-toxic towards A. salina at concentrations below 414, 564, 350, and 385 µM, respectively, and did not affect liver biochemical parameters, although pyknosis was induced in hepatocytes of the treated mice.


Assuntos
Complexos de Coordenação , Testes de Sensibilidade Microbiana , Bases de Schiff , Zinco , Bases de Schiff/química , Bases de Schiff/farmacologia , Zinco/química , Animais , Camundongos , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Complexos de Coordenação/síntese química , Cristalografia por Raios X , Artemia/efeitos dos fármacos , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Anti-Infecciosos/síntese química , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Escherichia coli/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Estrutura Molecular , Staphylococcus aureus/efeitos dos fármacos , Testes de Toxicidade Aguda
9.
Infect Genet Evol ; 126: 105702, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39657902

RESUMO

Pseudomonas aeruginosa, an opportunistic pathogen often found in Healthcare-associated infections (HAI), has shown increased resistance to carbapenems (imipenem, meropenem, doripenem), the primary treatment options. We've seen a rise in carbapenemase-producing P. aeruginosa in Brazil, including NDM-producers. This study characterises an isolate carrying blaNDM-1 from a patient's skin fragment in a Brazilian hospital. The whole genomic sequence (WGS) of P. aeruginosa CCBH26428 was extracted and sequenced using Illumina and minION platforms. The assembly used MinION results mapped with Illumina reads, and annotation was performed by the RAST server. Resistance genes and clonality were identified using the CABGen platform. Additional information was carried out by manual annotation using Geneious software and BLAST tool. The genomic analysis revealed a genome of 6.995.008 bp and G+C 65.9 %. P. aeruginosa CCBH26428 belongs to ST2407. The blaNDM gene, associated with ISAba125, was found in a 63.862 pb genomic region flanked by IS26 insertion sequences. This region also contained the repA of the plasmid incompatibility group IncC2 and other resistance genes, suggesting it is a possible "translocation unit". Additionally, 17 resistance genes, mutations in OprD and GyrA, and several virulence genes were detected, potentially exacerbating the infection. This study is report a WGS analysis of P. aeruginosa carrying blaNDM-1 in Brazil, highlighting the role of IS26 in the acquisition and spread of resistance genes between plasmids and chromosomes.


Assuntos
Infecções por Pseudomonas , Pseudomonas aeruginosa , beta-Lactamases , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/efeitos dos fármacos , beta-Lactamases/genética , Brasil , Humanos , Infecções por Pseudomonas/microbiologia , Genoma Bacteriano , Antibacterianos/farmacologia , Testes de Sensibilidade Microbiana , Sequenciamento Completo do Genoma , Genômica/métodos , Cromossomos Bacterianos/genética
10.
Sci Rep ; 14(1): 31283, 2024 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-39732799

RESUMO

Antimicrobial resistance (AMR) poses a significant global health challenge, necessitating advanced predictive models to support clinical decision-making. In this study, we explore multi-label classification as a novel approach to predict antibiotic resistance across four clinically relevant bacteria: E. coli, S. aureus, K. pneumoniae, and P. aeruginosa. Using multiple datasets from the DRIAMS repository, we evaluated the performance of four algorithms - Multi-Layer Perceptron, Support Vector Classifier, Random Forest, and Extreme Gradient Boosting - under both single-label and multi-label frameworks. Our results demonstrate that the multi-label approach delivers competitive performance compared to traditional single-label models, with no statistically significant differences in most cases. The multi-label framework naturally captures the complex, interconnected nature of AMR data, reflecting real-world scenarios more accurately. We further validated the models on external datasets (DRIAMS B and C), confirming their generalizability and robustness. Additionally, we investigated the impact of oversampling techniques and provided a reproducible methodology for handling MALDI-TOF data, ensuring scalability for future studies. These findings underscore the potential of multi-label classification to enhance predictive accuracy in AMR research, offering valuable insights for developing diagnostic tools and guiding clinical interventions.


Assuntos
Algoritmos , Antibacterianos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Antibacterianos/farmacologia , Humanos , Farmacorresistência Bacteriana , Escherichia coli/efeitos dos fármacos , Testes de Sensibilidade Microbiana/métodos , Staphylococcus aureus/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos
11.
Emerg Microbes Infect ; 13(1): 2420737, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39530158

RESUMO

Although an increased effectiveness has been suggested when phages and antibiotics are combined, this approach has not been tested against a mature biofilm on an endotracheal tube (ETT) surface. This study evaluated the effect of short- and long-term combined phage-antibiotic therapy in a control of a mature biofilm on an ETT surface. Pseudomonas aeruginosa strains, including susceptible and resistant clinical samples, were used to develop the ETT biofilm. Biofilm was treated with 108PFU/mL of phage_2, phage_18 or 5 µg/mL of ceftolozane/tazobactam, alone or in combination with phages. The sequential combination of the two different phages and ceftolozane/tazobactam was also tested. Biofilm viability was assessed after short (2, 4, 24 h) and long-(48, 72 h) term treatment exposure using colony forming unit measurement. For long-term exposition, a new treatment shot was added every 24 h. In the sequential combination, the phage type was switched at 24 h of treatment. Regarding the susceptible strains, the treatments had limited antibiofilm effect after 2, 4 and 24 h. After 48 and 72 h, administering phages alone had no effect on biofilm viability, indicating the emergence of phage-resistant phenotypes. Nonetheless, the combined phage-antibiotic treatment reduced the biofilm viability in about 5-log, whilst antibiotic alone reduced in about 3-log. The sequential combination of phages and antibiotic reduced the biofilm viability in about 6-log. With respect to the resistant strains, no antibiofilm activity was observed regarding the treatment arms. The combination of phages and ceftolozane/tazobactam showed a synergism strain-dependent, being more apparent in susceptible strains.


Assuntos
Antibacterianos , Biofilmes , Cefalosporinas , Infecções por Pseudomonas , Pseudomonas aeruginosa , Tazobactam , Biofilmes/efeitos dos fármacos , Pseudomonas aeruginosa/virologia , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/fisiologia , Tazobactam/farmacologia , Cefalosporinas/farmacologia , Antibacterianos/farmacologia , Humanos , Infecções por Pseudomonas/microbiologia , Infecções por Pseudomonas/terapia , Intubação Intratraqueal , Testes de Sensibilidade Microbiana , Fagos de Pseudomonas/fisiologia , Terapia por Fagos
12.
Rev Argent Microbiol ; 56(4): 368-372, 2024.
Artigo em Espanhol | MEDLINE | ID: mdl-39572364

RESUMO

Pseudomonas aeruginosa is a Gram-negative bacillus capable of developing in humid environments and animal tissue. The interest in this bacterium lies in its ability to cause opportunistic diseases in patients with cystic fibrosis and healthcare-associated infections (HAIs). The objective of our study was to characterize the resistance profile of strains causing HAIs isolated in hospitals within our community, from January 2019 to December 2021. This descriptive, prospective, and cross-sectional study involved the isolation of strains from January 2019 to December 2021 at the Autonomous University of Baja California (UABC). The identification of the strains was carried out using Matrix-Assisted Laser Desorption/Ionization-Time of Flight (MALDI-TOF) mass spectrometry, and the detection of beta-lactam resistance was performed according to the criteria of the Clinical and Laboratory Standards Institute as stipulated in the CLSI M100-S27 document. A total of 649 samples were obtained from January 2019 to December 2021, including sputum (335 samples), urine (119 samples), and wounds (91 samples). Resistance to carbapenems was 38.94% for meropenem and 21.97% for imipenem. For cephalosporins, there was a 21.05% resistance rate for cefepime, 22.9% for ceftazidime, and 24.78% for ceftolozane-tazobactam. The prevalence of antimicrobial resistance has increased over time, which is attributable to both selective pressure and the evolution of the microorganisms themselves.


Assuntos
Pseudomonas aeruginosa , Resistência beta-Lactâmica , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/isolamento & purificação , Estudos Transversais , Humanos , Estudos Prospectivos , Infecções por Pseudomonas/microbiologia , Infecções por Pseudomonas/epidemiologia , Infecção Hospitalar/microbiologia , Infecção Hospitalar/epidemiologia , México , Antibacterianos/farmacologia , Testes de Sensibilidade Microbiana
13.
J Wound Ostomy Continence Nurs ; 51(6): 445-453, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39588812

RESUMO

PURPOSE: The aim of the study was to analyze the characteristics of the biofilm of venous ulcers in terms of location and formation and to relate the presence of the biofilm to ulcer characteristics including duration, injured area, and necrotic tissue. DESIGN: Descriptive clinical study. MATERIALS AND METHODS: We obtained 2 biopsy fragments (tissue samples) from 44 patients with venous ulcers treated at a public outpatient clinic in a university hospital in Belo Horizonte, Brazil. Ulcers were photographed and classified according to the duration. In addition, the wound size and proportion of wound surface covered by necrotic tissue were measured. One fragment from each ulcer underwent microbiological analysis, while the other was analyzed using transmission electron microscopy. Data analysis was limited to fragments from patients with bacteria in the microbiological analysis. RESULTS: Data analysis is based on samples obtained from 21 ulcers in 21 patients who had bacteria in their ulcer based on microbiologic analysis of a tissue sample. Most ulcers were open for 2 to 10 years, 57% (n = 12) were 16 cm2 or smaller, and the proportion of the wound bed covered by necrotic tissue coverage varied widely. Of the 21/44 patients (48%) with bacteria in their ulcers, only 3 patients had bacterial biofilm present in the transmission electron microscopy, corresponding to 7% of the 44 patients. Pseudomonas aeruginosa was the most frequent bacterium, identified in 10 fragments. The biofilm was not present on the surface but in a layer slightly below it. The detection of biofilms was not directly related to the duration of the ulcer. It was not possible to establish a correlation between the size of the lesion and the presence of these microorganisms due to the small sample size. CONCLUSIONS: Our findings indicate that detecting biofilm in venous ulcers is challenging, as it does not uniformly occur throughout the wound bed, can occur at different depths, and is often not present on the wound surface. There is a need to develop studies that can contribute to the detection of biofilm in clinical practice.


Assuntos
Biofilmes , Úlcera Varicosa , Humanos , Úlcera Varicosa/microbiologia , Úlcera Varicosa/fisiopatologia , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Brasil , Cicatrização/fisiologia , Idoso de 80 Anos ou mais , Pseudomonas aeruginosa/patogenicidade , Adulto
14.
Biofouling ; 40(10): 735-742, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39380146

RESUMO

Microbiologically contaminated water is a significant source of infections in humans and animals, with Pseudomonas aeruginosa (PSA) being particularly concerning due to its ability to thrive in water environments and its resistance to many disinfectants. Therefore, this study investigates the adhesion potential of PSA strains on various materials used in mineral water extraction wells, focusing on hydrophobic and hydrophilic properties. Mineral water samples were collected from three wells (P-01, P-07, and P-08) within the Guarani Aquifer System and Fractured Aquifer System (SAF) in Brazil. The physicochemical properties of the water, including concentrations of Sr (strontium), Fe (iron), Si (silicon), SO42- (sulfate ions), Cl- (chloride ions), and ORP (oxidation-reduction potential), were analyzed. Results indicated higher PSA adhesion on hydrophobic materials, particularly high-density polyethylene (HDPE) and geomechanically plasticized polyvinyl chloride (PVC). Multiple correlation analyses revealed positive correlations between PSA adhesion on hydrophilic materials and Sr, Fe, Si, SO42-, and Cl- concentrations. Conversely, ORP negatively correlated with bacterial adhesion on PVC surfaces, suggesting higher ORP values reduced PSA attachment. These findings highlight the importance of water composition and material properties in influencing bacterial adhesion and potential biofilm formation in mineral water extraction systems.


Assuntos
Aderência Bacteriana , Interações Hidrofóbicas e Hidrofílicas , Águas Minerais , Pseudomonas aeruginosa , Propriedades de Superfície , Pseudomonas aeruginosa/fisiologia , Águas Minerais/microbiologia , Poços de Água , Biofilmes , Brasil , Microbiologia da Água
15.
Microb Pathog ; 197: 107019, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39442815

RESUMO

Agroindustrial wastes are generated daily and seem to be rich in bioactive molecules. Thus, they can potentially be used as source of compounds able to control bacterial biofilms. We investigated the potential of extracts from the residues of rice and grape to combat clinically important bacterial biofilms. Extracts of grape pomace and rice bran were obtained using different extractive methodologies and subjected to the evaluation of its antimicrobial and antibiofilm activities. After the in vivo toxicity, the chemical characterization of the most promising extract was assessed. The mass spectrometry analysis revealed the presence of dipeptides, alkaloids and phenolic compounds. Most grape extracts presented antibiofilm and antimicrobial activities against Staphylococcus epidermidis ATCC 35984 and Pseudomonas aeruginosa PA14. The hydromethanolic grape pomace extract obtained by ultrasound assisted extraction (MeOH 80 UAE) presented the most promising activity, being able to inhibit in 99 % and 80 % the biofilm formation of S. epidermidis and P. aeruginosa, respectively. Against the gram-negative model, this extract eradicated the biofilm by 80 %, induced the swarming motility and displayed a physical effect. It also did not present acute or chronic toxicity in Caenorhabditis elegans model. In this way, agroindustrial residues represent a promising source of molecules capable of controlling bacterial biofilms.


Assuntos
Antibacterianos , Biofilmes , Caenorhabditis elegans , Testes de Sensibilidade Microbiana , Oryza , Extratos Vegetais , Pseudomonas aeruginosa , Staphylococcus epidermidis , Vitis , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Staphylococcus epidermidis/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/fisiologia , Oryza/microbiologia , Caenorhabditis elegans/efeitos dos fármacos , Vitis/química , Animais , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Antibacterianos/farmacologia , Antibacterianos/química
16.
Microb Pathog ; 197: 107079, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39454803

RESUMO

Bacteria coordinate gene expression in a cell density-dependent manner using a communication process called quorum sensing (QS). The expression of virulence factors, biofilm formation and enzyme production are examples of QS-regulated phenotypes that can interfere with food quality and safety. Due to the importance of these phenotypes, the inhibition of bacterial communication as an anti-virulence strategy is of great interest. This work aimed to evaluate the effect of phenolic compounds on the inhibition of biofilm formation by Pseudomonas aeruginosa PAO1, using concentrations that do not interfere in bacterial growth. The synergistic effect of rosmarinic acid, baicalein, curcumin and resveratrol with tobramycin and between the phenolics themselves was evaluated. The tested combinations proved to be a good strategy for reducing the dose of antibiotics used in treatments and obtaining satisfactory results against P. aeruginosa biofilms. The combination of the four compounds at the highest concentration (500 µM) completely inhibited biofilm formation. The obtained results contribute to understanding the effect of phenolic compounds on QS inhibition, which may help to define the mechanism of inhibition, in addition to expanding the biotechnological potential of these compounds for future applications in the food, pharmaceutical and medical fields.


Assuntos
Antibacterianos , Biofilmes , Depsídeos , Sinergismo Farmacológico , Flavanonas , Fenóis , Pseudomonas aeruginosa , Percepção de Quorum , Resveratrol , Ácido Rosmarínico , Tobramicina , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Pseudomonas aeruginosa/efeitos dos fármacos , Tobramicina/farmacologia , Antibacterianos/farmacologia , Percepção de Quorum/efeitos dos fármacos , Fenóis/farmacologia , Depsídeos/farmacologia , Resveratrol/farmacologia , Flavanonas/farmacologia , Curcumina/farmacologia , Cinamatos/farmacologia , Testes de Sensibilidade Microbiana , Fatores de Virulência
17.
Photochem Photobiol Sci ; 23(11): 2029-2044, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39470974

RESUMO

Ultraviolet A (UVA) radiation is the major fraction of UV radiation reaching the Earth's surface. Its harmful effects on microorganisms, due mainly to oxidative damage, have been exploited for development of natural solar and commercial UVA-based disinfection methods. In this work, the global transcriptional response of Pseudomonas aeruginosa exposed to ultraviolet A (UVA) radiation was analyzed. To conduct this study, we analyzed the whole transcriptome of the PAO1 strain grown to logarithmic phase under sublethal doses of UVA or in the dark. We found that a total of 298 genes responded to UVA with a change of at least two-fold (5.36% of the total P. aeruginosa genome), and showed equal amount of induced and repressed genes. An important fraction of the induced genes were involved in the response to DNA damage and included induction of SOS, prophage and pyocins genes. The results presented in this study suggest that one of the main UVA targets are proteins carrying [Fe-S] clusters since several genes involved in the processes of synthesis, trafficking and assembly of these structures were upregulated. The management of intracellular iron levels also seems to be a robust response to this stress factor. The strong induction of genes involved in denitrification suggest that this pathway and/or reactive nitrogen species such as nitric oxide could have a role in the response to this radiation. Regarding the down-regulated genes, we found many involved in the biosynthesis of PQS, a quorum-sensing signal molecule with a possible role as endogenous photosensitizer.


Assuntos
Pseudomonas aeruginosa , Raios Ultravioleta , Pseudomonas aeruginosa/metabolismo , Pseudomonas aeruginosa/efeitos da radiação , Pseudomonas aeruginosa/genética , Transcrição Gênica/efeitos da radiação , Regulação Bacteriana da Expressão Gênica/efeitos da radiação , Dano ao DNA , Transcriptoma/efeitos da radiação
18.
mBio ; 15(12): e0250524, 2024 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-39475236

RESUMO

Serratia marcescens, a member of the Enterobacteriaceae family, is an opportunistic human pathogen and a frequent cause of urinary tract infections. Clinical isolates often exhibit resistance to multiple antibiotics, posing challenges for successful treatment. Understanding its pathogenic mechanisms is crucial for elucidating new potential targets to develop effective therapeutic interventions and manage S. marcescens infections. This work identifies urea-induced lactonase of Serratia (UilS), a lactonase encoded in the S. marcescens RM66262 strain isolated from a patient with a urinary tract infection. The study explores the bacterium's response to urea, a major component of urine, and its impact on uilS expression. We found that UilS degrades acyl-homoserine lactones (AHL) autoinducers traditionally associated with quorum sensing mechanisms. Surprisingly, UilS is able to degrade self and non-self AHL, exhibiting quorum-quenching activity toward Pseudomonas aeruginosa. We found that LuxR regulates uilS expression that is enhanced in the presence of AHL. In addition, urea-dependent induction of UilS expression is controlled by the transcriptional response regulator CpxR. UilS confers fitness advantage to S. marcescens, especially in the presence of urea, emphasizing the adaptive plasticity of strains to modulate gene expression based on environmental signals and population density. We also discovered a novel bacterial killing capacity of S. marcescens that involves UilS, indicating its importance in the interspecies interaction of Serratia. Finally, we found that a uilS mutant strain displays attenuated colonization in a mouse model of catheter-associated urinary tract infection. uilS is present in clinical but absent in environmental isolates, suggesting an evolutionary adaptation to host-specific selective pressures. IMPORTANCE: This work reveals the acyl-homoserine lactonase urea-induced lactonase of Serratia as a novel virulence factor of Serratia marcescens, unraveling a potential target to develop antimicrobial strategies and shedding light on the complex regulatory network governing pathogenicity and adaptation to host environments.


Assuntos
Percepção de Quorum , Infecções por Serratia , Serratia marcescens , Ureia , Infecções Urinárias , Serratia marcescens/genética , Serratia marcescens/enzimologia , Serratia marcescens/efeitos dos fármacos , Serratia marcescens/fisiologia , Infecções Urinárias/microbiologia , Animais , Camundongos , Ureia/farmacologia , Ureia/metabolismo , Infecções por Serratia/microbiologia , Humanos , Hidrolases de Éster Carboxílico/genética , Hidrolases de Éster Carboxílico/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Regulação Bacteriana da Expressão Gênica , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/enzimologia , Feminino , Acil-Butirolactonas/metabolismo , Interações Microbianas
19.
Sci Data ; 11(1): 1105, 2024 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-39384817

RESUMO

This data descriptor presents a curated dataset for pathogen detection and identification (Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans) directly from whole-blood samples. The dataset was created using differential cell lysis combined with rapid extraction, digestion, and mass spectrometry-based proteomics. Our method offers a rapid diagnostic alternative to traditional culture, enabling timely disease management, such as sepsis. Highlighting our dataset's uniqueness, it features a three-tier structure: Spectral Libraries of Pathogens for identifying peptide peaks for putative biomarkers; Spiked pathogen in blood MS data for biomarker panel optimization through varied concentration samples; and Parallel Reaction Monitoring (PRM) data from sepsis patients for validating our biomarker panel, achieving 83.3% sensitivity within seven hours without microbial enrichment culture. This dataset serves as a comprehensive reference for bioinformatic tool development and biomarker panel proposals, advancing microbial detection, antimicrobial resistance, and epidemiological studies.


Assuntos
Biomarcadores , Candida albicans , Proteômica , Pseudomonas aeruginosa , Sepse , Staphylococcus aureus , Humanos , Proteômica/métodos , Biomarcadores/sangue , Sepse/sangue , Sepse/diagnóstico , Sepse/microbiologia , Espectrometria de Massas
20.
Future Med Chem ; 16(21): 2247-2261, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39400207

RESUMO

Aim: This work describes the synthesis and antimicrobial evaluation of 6-aminated 1,4-benzoquinones (6-AQs) against seven resistant pathogens.Materials & methods: The 6-AQs, synthesized via a Michael addition reaction between bromoquinone and p-substituted anilines, were assessed for their antimicrobial activity through both in vitro and in silico analyses.Results: Bromoquinone and 6-AQs with electron-withdrawing groups demonstrated activity against Pseudomonas aeruginosa, with minimum inhibitory concentrations ranging from 16 to 128 µg/ml, comparable to standard antimicrobials. Two derivatives exhibited minimum inhibitory concentrations values against methicillin-resistant Staphylococcus aureus ranging from 64 to 128 µg/ml. These compounds demonstrated both bacteriostatic and bactericidal effects, and antibiofilm features.Conclusion: The 6-AQs 19g and 19f showed a promising antimicrobial profile, indicating their potential as new therapeutic options.


[Box: see text].


Assuntos
Antibacterianos , Benzoquinonas , Biofilmes , Staphylococcus aureus Resistente à Meticilina , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa , Antibacterianos/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Biofilmes/efeitos dos fármacos , Benzoquinonas/química , Benzoquinonas/farmacologia , Benzoquinonas/síntese química , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Relação Estrutura-Atividade , Estrutura Molecular
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA