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1.
Arch Microbiol ; 206(3): 91, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38316691

RESUMO

Inhibition of quorum sensing is considered to be an effective strategy of control and treatment of a wide range of acute and persistent infections. Pseudomonas aeruginosa is an opportunistic bacterium with a high adaptation potential that contributes to healthcare-associated infections. In the present study, the effects of the synthesized hybrid structures bearing sterically hindered phenolic and heterocyclic moieties in a single scaffold on the production of virulence factors by P. aeruginosa were determined. It has been shown that the obtained compounds significantly reduce both pyocyanin and alginate production and stimulate the biosynthesis of siderophores in vitro, which may be attributed to their iron-chelating properties. The results of docking-based inverse high-throughput virtual screening indicate that transcription regulator LasR and Cu-transporter OPRC could be potential molecular targets for these compounds. Investigation of the impact small molecules exert on the molecular mechanisms of the production of bacterial virulence factors may pave the way for the design and development of novel antibacterial agents.


Assuntos
Pseudomonas aeruginosa , Fatores de Virulência , Transativadores/farmacologia , Percepção de Quorum , Piocianina , Proteínas de Bactérias/genética , Proteínas de Bactérias/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Biofilmes
3.
Microb Pathog ; 188: 106562, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38307370

RESUMO

Bacterial outer membrane vesicles (OMVs) can package and deliver virulence factors into host cells, which is an important mechanism mediating host-pathogen interactions. It has been reported that small RNAs (sRNAs) can be packed into OMVs with varying relative abundance, which might affect the function and/or stability of host mRNAs. In this study, we used OptiPrep density gradient ultra-high-speed centrifugation to purify OMVs from Pseudomonas aeruginosa. Next, the sequences and abundance of sRNAs were detected by using Small RNA-Seq. In particular, sRNA4518698, sRNA2316613 and sRNA809738 were the three most abundant sRNAs in OMVs, which are all fragments of P. aeruginosa non-coding RNAs. sRNAs were shielded within the interior of OMVs and remained resistant to external RNase cleavage. The miRanda and RNAhybrid analysis demonstrated that those sRNAs could target a large number of host mRNAs, which were enriched in host immune responses by the functions of GO and KEGG enrichment. Experimentally, we demonstrated that the transfection of synthetic sRNA4518698, sRNA2316613, or sRNA809738 could reduce the expression of innate immune response genes in RAW264.7 cells. Together, we demonstrated that P. aeruginosa OMVs sRNAs can regulate innate immune responses. This study uncovered a mechanism in which the OMVs regulate host responses by transferring bacterial sRNAs.


Assuntos
Infecções por Pseudomonas , Pseudomonas aeruginosa , Humanos , Pseudomonas aeruginosa/fisiologia , Infecções por Pseudomonas/microbiologia , Imunidade Inata , RNA Bacteriano/genética , RNA Bacteriano/metabolismo , Interações Hospedeiro-Patógeno , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
4.
Enzyme Microb Technol ; 175: 110408, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38309052

RESUMO

Alginate lyases with unique characteristics for degrading alginate into size-defined oligosaccharide fractions, were considered as the potential agents for disrupting Pseudomonas aeruginosa biofilms. In our study, a novel endolytic PL-7 alginate lyase, named AlyG2, was cloned and expressed through Escherichia coli. This enzyme exhibited excellent properties: it maintained more than 85% activity at low temperatures of 4 °C and high temperatures of 70 °C. After 1 h of incubation at 4 °C, it still retained over 95% activity, demonstrating the ability to withstand low temperature. The acid-base and salt tolerance properties shown it preserves more than 50% activity in the pH range of 5.0 to 11.0 and in a high salt environment at 3000 mM NacCl, indicating its high stability in several aspects. More importantly, AlyG2 in our research was revealed to be effective at removing mature biofilms and inhibiting biofilm formation produced by Pseudomonas aeruginosa, and the inhibition and disruption rates were 47.25 ± 4.52% and 26.5 ± 6.72%, respectively. Additionally, the enzyme AlyG2 promoted biofilm disruption in combination with antibiotics, particularly manifesting the synergistic effect with erythromycin (FIC=0.5). In all, these results offered that AlyG2 with unique characteristics may be an effective technique for the clearance or disruption of biofilm produced by P. aeruginosa.


Assuntos
Biofilmes , Flavobacteriaceae , Pseudomonas aeruginosa , Pseudomonas aeruginosa/genética , Polissacarídeo-Liases/genética , Polissacarídeo-Liases/química , Alginatos
5.
Microb Genom ; 10(2)2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38421269

RESUMO

Pseudomonas aeruginosa, a harmful nosocomial pathogen associated with cystic fibrosis and burn wounds, encodes for a large number of LysR-type transcriptional regulator proteins. To understand how and why LTTR proteins evolved with such frequency and to establish whether any relationships exist within the distribution we set out to identify the patterns underpinning LTTR distribution in P. aeruginosa and to uncover cluster-based relationships within the pangenome. Comparative genomic studies revealed that in the JGI IMG database alone ~86 000 LTTRs are present across the sequenced genomes (n=699). They are widely distributed across the species, with core LTTRs present in >93 % of the genomes and accessory LTTRs present in <7 %. Analysis showed that subsets of core LTTRs can be classified as either variable (typically specific to P. aeruginosa) or conserved (and found to be distributed in other Pseudomonas species). Extending the analysis to the more extensive Pseudomonas database, PA14 rooted analysis confirmed the diversification patterns and revealed PqsR, the receptor for the Pseudomonas quinolone signal (PQS) and 2-heptyl-4-quinolone (HHQ) quorum-sensing signals, to be amongst the most variable in the dataset. Successful complementation of the PAO1 pqsR - mutant using representative variant pqsR sequences suggests a degree of structural promiscuity within the most variable of LTTRs, several of which play a prominent role in signalling and communication. These findings provide a new insight into the diversification of LTTR proteins within the P. aeruginosa species and suggests a functional significance to the cluster, conservation and distribution patterns identified.


Assuntos
Fibrose Cística , Infecções por Pseudomonas , Humanos , Pseudomonas aeruginosa/genética , Genômica , Pseudomonas , Fibrose Cística/genética
6.
Indian J Pathol Microbiol ; 67(1): 51-55, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38358188

RESUMO

Background: Secondary bacterial infections during COVID-19 hospitalization have been reported in about 6-15% of patients. Aims: To study the secondary bacterial infections that affected the COVID-19 patients during their hospitalisation and to unearth the bacteriological profile of samples obtained after their demise. Settings and Design: This prospective study was carried out at a COVID-19 dedicated, apex tertiary care centre in North India from July 2020 to April 2021. Methods and Materials: Samples of 268 patients were considered for the study. Nasopharyngeal swab specimen, blood, and tissue (lung) were collected from the deceased body as early as possible and processed. Statistical Analysis: Statistical analyses were performed using STATA version 11.1 (Stata Corp., College Station, TX, USA). Results: A total of 170 samples were received from patients before their death, which included blood, urine, respiratory samples, pus, and cerebrospinal fluid. Forty-four pathogens were isolated, which consisted of Acinetobacter baumannii (43.1%), Klebsiella pneumoniae (36.3%), Escherichia coli (11.3%), and Pseudomonas aeruginosa (4.5%), Enterococcus faecium (4.5%). Two hundred fifty-eight samples were collected from the deceased bodies wherein the nasopharyngeal sample was highest, followed by tissue and blood. A total of 43 pathogens were isolated among them which included A. baumannii (44.1%), followed by K. pneumoniae (25.5%), E. coli (20.9%), P. aeruginosa (6.97%) and Enterobacter cloacae (2.3%). All these isolates were highly resistant to antimicrobials. Conclusions: In our study, bacterial profiles in antemortem and postmortem samples were found to be similar, suggesting that resistant pathogens may be the cause of mortality in COVID-19 infected hospitalised patients.


Assuntos
Infecções Bacterianas , COVID-19 , Coinfecção , Humanos , Escherichia coli , Estudos Prospectivos , Klebsiella pneumoniae , Bactérias , Infecções Bacterianas/epidemiologia , Pseudomonas aeruginosa , Antibacterianos/uso terapêutico , Testes de Sensibilidade Microbiana
7.
Respir Res ; 25(1): 90, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38355515

RESUMO

BACKGROUND: Exposure to PM2.5 has been implicated in a range of detrimental health effects, particularly affecting the respiratory system. However, the precise underlying mechanisms remain elusive. METHODS: To address this objective, we collected ambient PM2.5 and administered intranasal challenges to mice, followed by single-cell RNA sequencing (scRNA-seq) to unravel the heterogeneity of neutrophils and unveil their gene expression profiles. Flow cytometry and immunofluorescence staining were subsequently conducted to validate the obtained results. Furthermore, we assessed the phagocytic potential of neutrophils upon PM2.5 exposure using gene analysis of phagocytosis signatures and bacterial uptake assays. Additionally, we utilized a mouse pneumonia model to evaluate the susceptibility of PM2.5-exposed mice to Pseudomonas aeruginosa infection. RESULTS: Our study revealed a significant increase in neutrophil recruitment within the lungs of PM2.5-exposed mice, with subclustering of neutrophils uncovering subsets with distinct gene expression profiles. Notably, exposure to PM2.5 was associated with an expansion of PD-L1high neutrophils, which exhibited impaired phagocytic function dependent upon PD-L1 expression. Furthermore, PM2.5 exposure was found to increase the susceptibility of mice to Pseudomonas aeruginosa, due in part to increased PD-L1 expression on neutrophils. Importantly, monoclonal antibody targeting of PD-L1 significantly reduced bacterial burden, dissemination, and lung inflammation in PM2.5-exposed mice upon Pseudomonas aeruginosa infection. CONCLUSIONS: Our study suggests that PM2.5 exposure promotes expansion of PD-L1high neutrophils with impaired phagocytic function in mouse lungs, contributing to increased vulnerability to bacterial infection, and therefore targeting PD-L1 may be a therapeutic strategy for reducing the harmful effects of PM2.5 exposure on the immune system.


Assuntos
Pneumonia , Infecções por Pseudomonas , Animais , Camundongos , Neutrófilos/metabolismo , Material Particulado/toxicidade , Infecções por Pseudomonas/microbiologia , Antígeno B7-H1/metabolismo , Pulmão , Pneumonia/metabolismo , Pseudomonas aeruginosa
8.
Ann Clin Microbiol Antimicrob ; 23(1): 13, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38347529

RESUMO

BACKGROUND: Recently, extensively drug-resistant Pseudomonas aeruginosa (XDR-PA) isolates have been increasingly detected and posed great challenges to clinical anti-infection treatments. However, little is known about extensively resistant hypervirulent P. aeruginosa (XDR-hvPA). In this study, we investigate its epidemiological characteristics and provide important basis for preventing its dissemination. METHODS: Clinical XDR-PA isolates were collected from January 2018 to January 2023 and identified using matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry; antibiotic susceptibility testing was performed by broth microdilution method, and minimum inhibitory concentrations (MICs) were evaluated. Virulence was evaluated using the Galleria mellonella infection model; molecular characteristics, including resistance genes, virulence genes, and homology, were determined using whole-genome sequencing. RESULTS: A total of 77 XDR-PA strains were collected; 47/77 strains were XDR-hvPA. Patients aged > 60 years showed a significantly higher detection rate of XDR-hvPA than of XDR-non-hvPA. Among the 47 XDR-hvPA strains, 24 strains carried a carbapenemase gene, including blaGES-1 (10/47), blaVIM-2 (6/47), blaGES-14 (4/47), blaIMP-45 (2/47), blaKPC-2 (1/47), and blaNDM-14 (1/47). ExoU, exoT, exoY, and exoS, important virulence factors of PA, were found in 31/47, 47/47, 46/47, and 29/47 strains, respectively. Notably, two XDR-hvPA simultaneously co-carried exoU and exoS. Six serotypes (O1, O4-O7, and O11) were detected; O11 (19/47), O7 (13/47), and O4 (9/47) were the most prevalent. In 2018-2020, O4 and O7 were the most prevalent serotypes; 2021 onward, O11 (16/26) was the most prevalent serotype. Fourteen types of ST were detected, mainly ST235 (14/47), ST1158 (13/47), and ST1800 (7/47). Five global epidemic ST235 XDR-hvPA carried blaGES and showed the MIC value of ceftazidime/avibactam reached the susceptibility breakpoint (8/4 mg/L). CONCLUSIONS: The clinical detection rate of XDR-hvPA is unexpectedly high, particularly in patients aged > 60 years, who are seemingly more susceptible to contracting this infection. Clonal transmission of XDR-hvPA carrying blaGES, which belongs to the global epidemic ST235, was noted. Therefore, the monitoring of XDR-hvPA should be strengthened, particularly for elderly hospitalized patients, to prevent its spread.


Assuntos
Antibacterianos , Infecções por Pseudomonas , Idoso , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Pseudomonas aeruginosa/genética , Infecções por Pseudomonas/epidemiologia , Infecções por Pseudomonas/tratamento farmacológico , Proteínas de Bactérias/genética , beta-Lactamases/genética , Sorogrupo , China/epidemiologia , Testes de Sensibilidade Microbiana , Farmacorresistência Bacteriana Múltipla/genética
9.
mSphere ; 9(2): e0055323, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38299825

RESUMO

The bacteriophage is an effective adjunct to existing antibiotic therapy; however, in the course of bacteriophage therapy, host bacteria will develop resistance to bacteriophages, thus affecting the efficacy. Therefore, it is important to describe how bacteria evade bacteriophage attack and the consequences of the biological changes that accompany the development of bacteriophage resistance before the bacteriophage is applied. The specific bacteriophage vB3530 of Pseudomonas aeruginosa (P. aeruginosa) has stable biological characteristics, short incubation period, strong in vitro cleavage ability, and absence of virulence or resistance genes. Ten bacteriophage-resistant strains (TL3780-R) were induced using the secondary infection approach, and the plaque assay showed that vB3530 was less sensitive to TL3780-R. Identification of bacteriophage adsorption receptors showed that the bacterial surface polysaccharide was probably the adsorption receptor of vB3530. In contrast to the TL3780 parental strain, TL3780-R is characterized by the absence of long lipopolysaccharide chains, which may be caused by base insertion of wzy or deletion of galU. It is also intriguing to observe that, in comparison to the parent strain, the bacteriophage-resistant strains TL3780-R mostly exhibited a large cost of fitness (growth rate, biofilm formation, motility, and ability to produce enhanced pyocyanin). In addition, TL3780-R9 showed increased susceptibility to aminoglycosides and chlorhexidine, which may be connected to the loss and down-regulation of mexX expression. Consequently, these findings fully depicted the resistance mechanism of P. aeruginosa to vB3530 and the fitness cost of bacteriophage resistance, laying a foundation for further application of bacteriophage therapy.IMPORTANCEThe bacteriophage is an effective adjunct to existing antibiotic therapy; However, bacteria also develop defensive mechanisms against bacteriophage attack. Thus, there is an urgent need to deeply understand the resistance mechanism of bacteria to bacteriophages and the fitness cost of bacteriophage resistance so as to lay the foundation for subsequent application of the phage. In this study, a specific bacteriophage vB3530 of P. aeruginosa had stable biological characteristics, short incubation period, strong in vitro cleavage ability, and absence of virulence or resistance genes. In addition, we found that P. aeruginosa may lead to phage resistance due to the deletion of galU and the base insertion of wzy, involved in the synthesis of lipopolysaccharides. Simultaneously, we showed the association with the biological state of the bacteria after bacteria acquire bacteriophage resistance, which is extremely relevant to guide the future application of therapeutic bacteriophages.


Assuntos
Bacteriófagos , Infecções por Pseudomonas , Humanos , Bacteriófagos/genética , Pseudomonas aeruginosa , Infecções por Pseudomonas/terapia , Infecções por Pseudomonas/microbiologia , Antibacterianos/farmacologia , Virulência
10.
mSphere ; 9(2): e0067723, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38305166

RESUMO

The outer membrane (OM) is an essential structure of Gram-negative bacteria that provides mechanical strength and protection from large and/or hydrophobic toxic molecules, including many antibiotics. The OM is composed of glycerophospholipids (GPLs) and lipopolysaccharide (LPS) in the inner and outer leaflets, respectively, and hosts integral ß-barrel proteins and lipoproteins. While the systems responsible for translocation and insertion of LPS and OM proteins have been elucidated, the mechanism(s) mediating transport of GPLs from the inner membrane to the OM has remained elusive for decades. Very recently, studies performed in Escherichia coli proposed a role in this process for AsmA-like proteins that are predicted to share structural features with eukaryotic lipid transporters. In this study, we provide the first systematic investigation of AsmA-like proteins in a bacterium other than E. coli, the opportunistic human pathogen Pseudomonas aeruginosa. Bioinformatic analyses revealed that P. aeruginosa possesses seven AsmA-like proteins. Deletion of asmA-like genes in many different combinations, coupled with conditional mutagenesis, revealed that four AsmA-like proteins are redundantly essential for growth and OM integrity in P. aeruginosa, including a novel AsmA-like protein (PA4735) that is not present in E. coli. Cells depleted of AsmA-like proteins showed severe defects in the OM permeability barrier that were partially rescued by lowering the synthesis or transport of LPS. Since fine balancing of GPL and LPS levels is crucial for OM integrity, this evidence supports the role of AsmA-like proteins in GPL transport toward the OM. IMPORTANCE: Given the importance of the outer membrane (OM) for viability and antibiotic resistance in Gram-negative bacteria, in the last decades, several studies have focused on the characterization of the systems involved in OM biogenesis, which have also been explored as targets for antibacterial drug development. However, the mechanism mediating translocation of glycerophospholipids (GPLs) to the OM remained unknown until recent studies provided evidence that AsmA-like proteins could be responsible for this process. Here, we demonstrate for the first time that AsmA-like proteins are essential and redundant for growth and OM integrity in a Gram-negative bacterium other than the model organism Escherichia coli and demonstrate that the human pathogen Pseudomonas aeruginosa has an additional essential AsmA-like protein that is not present in E. coli, thus expanding the range of AsmA-like proteins that play key functions in Gram-negative bacteria.


Assuntos
Escherichia coli , Pseudomonas aeruginosa , Humanos , Escherichia coli/genética , Escherichia coli/metabolismo , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/metabolismo , Lipopolissacarídeos/metabolismo , Proteínas da Membrana Bacteriana Externa/genética , Proteínas da Membrana Bacteriana Externa/metabolismo , Antibacterianos/metabolismo , Glicerofosfolipídeos/metabolismo
11.
PLoS Biol ; 22(2): e3002205, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38300958

RESUMO

Cells must access resources to survive, and the anatomy of multicellular structures influences this access. In diverse multicellular eukaryotes, resources are provided by internal conduits that allow substances to travel more readily through tissue than they would via diffusion. Microbes growing in multicellular structures, called biofilms, are also affected by differential access to resources and we hypothesized that this is influenced by the physical arrangement of the cells. In this study, we examined the microanatomy of biofilms formed by the pathogenic bacterium Pseudomonas aeruginosa and discovered that clonal cells form striations that are packed lengthwise across most of a mature biofilm's depth. We identified mutants, including those defective in pilus function and in O-antigen attachment, that show alterations to this lengthwise packing phenotype. Consistent with the notion that cellular arrangement affects access to resources within the biofilm, we found that while the wild type shows even distribution of tested substrates across depth, the mutants show accumulation of substrates at the biofilm boundaries. Furthermore, we found that altered cellular arrangement within biofilms affects the localization of metabolic activity, the survival of resident cells, and the susceptibility of subpopulations to antibiotic treatment. Our observations provide insight into cellular features that determine biofilm microanatomy, with consequences for physiological differentiation and drug sensitivity.


Assuntos
Antibacterianos , Infecções por Pseudomonas , Humanos , Antibacterianos/farmacologia , Pseudomonas aeruginosa/metabolismo , Biofilmes , Infecções por Pseudomonas/microbiologia , Fímbrias Bacterianas
12.
PeerJ ; 12: e16826, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38313021

RESUMO

This study aimed to investigate the potential of patuletin, a rare natural flavonoid, as a virulence and LasR inhibitor against Pseudomonas aeruginosa. Various computational studies were utilized to explore the binding of Patuletin and LasR at a molecular level. Molecular docking revealed that Patuletin strongly interacted with the active pocket of LasR, with a high binding affinity value of -20.96 kcal/mol. Further molecular dynamics simulations, molecular mechanics generalized Born surface area (MM/GBSA), protein-ligand interaction profile (PLIP), and essential dynamics analyses confirmed the stability of the patuletin-LasR complex, and no significant structural changes were observed in the LasR protein upon binding. Key amino acids involved in binding were identified, along with a free energy value of -26.9 kcal/mol. In vitro assays were performed to assess patuletin's effects on P. aeruginosa. At a sub-inhibitory concentration (1/4 MIC), patuletin significantly reduced biofilm formation by 48% and 42%, decreased pyocyanin production by 24% and 14%, and decreased proteolytic activities by 42% and 20% in P. aeruginosa isolate ATCC 27853 (PA27853) and P. aeruginosa clinical isolate (PA1), respectively. In summary, this study demonstrated that patuletin effectively inhibited LasR activity in silico and attenuated virulence factors in vitro, including biofilm formation, pyocyanin production, and proteolytic activity. These findings suggest that patuletin holds promise as a potential therapeutic agent in combination with antibiotics to combat antibiotic-tolerant P. aeruginosa infections.


Assuntos
Biofilmes , Cromonas , Flavonas , Virulência , Pseudomonas aeruginosa , Percepção de Quorum , Simulação de Acoplamento Molecular , Piocianina/metabolismo , Flavonas/farmacologia
14.
Sci Rep ; 14(1): 2657, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-38302552

RESUMO

Bacteriophage therapy is one potential strategy to treat antimicrobial resistant or persistent bacterial infections, and the year 2021 marked the centennial of Felix d'Hérelle's first publication on the clinical applications of phages. At the Center for Phage Biology & Therapy at Yale University, a preparatory modular approach has been established to offer safe and potent phages for single-patient investigational new drug applications while recognizing the time constraints imposed by infection(s). This study provides a practical walkthrough of the pipeline with an Autographiviridae phage targeting Pseudomonas aeruginosa (phage vB_PaeA_SB, abbreviated to ΦSB). Notably, a thorough phage characterization and the evolutionary selection pressure exerted on bacteria by phages, analogous to antibiotics, are incorporated into the pipeline.


Assuntos
Bacteriófagos , Terapia por Fagos , Infecções por Pseudomonas , Fagos de Pseudomonas , Humanos , Pseudomonas aeruginosa , Universidades , Fagos de Pseudomonas/genética , Infecções por Pseudomonas/terapia , Infecções por Pseudomonas/microbiologia
15.
Ugeskr Laeger ; 186(3)2024 Jan 22.
Artigo em Dinamarquês | MEDLINE | ID: mdl-38305316

RESUMO

We present a case report detailing therapeutic application of two lytic antipseudomonal bacteriophages to treat a chronic relapsing Pseudomonas aeruginosa infection of a prosthetic aortic graft. As there are currently no Danish laboratories offering phages for clinical therapy, and this case, to our knowledge represents the first applied phage therapy in Denmark, the practical and regulatory aspects of offering this treatment option in Denmark is briefly reviewed along with the clinical case.


Assuntos
Bacteriófagos , Fagos de Pseudomonas , Humanos , Pseudomonas , Prótese Vascular , Pseudomonas aeruginosa
16.
World J Microbiol Biotechnol ; 40(3): 86, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38319399

RESUMO

In this study salicylic acid loaded containing selenium nanoparticles was synthesized and called SA@CS-Se NPs. the chitosan was used as a natural stabilizer during the synthesis process. Fourier transforms infrared spectroscopy (FTIR), Powder X-ray diffraction (XRD), field emission electron microscopy (FESEM), and transmission electron microscopy (TEM) were used to describe the physicochemical characteristics of the SA@CS-Se NPs. The PXRD examination revealed that the grain size was around 31.9 nm. TEM and FESEM techniques showed the spherical shape of SA@CS-Se NPs. Additionally, the analysis of experiments showed that SA@CS-Se NPs have antibacterial properties against 4 ATCC bacteria; So that with concentrations of 75, 125, 150, and 100 µg/ml, it inhibited the biofilm formation of Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, and Staphylococcus aureus respectively. Also, at the concentration of 300 µg/ml, it removed 22.76, 23.2, 10.62, and 18.08% biofilm caused by E. coli, P. aeruginosa, B. subtilis, and S. aureus respectively. The synthesized SA@CS-Se NPs may find an application to reduce the unsafe influence of pathogenic microbes and, hence, eliminate microbial contamination.


Assuntos
Anti-Infecciosos , Quitosana , Nanopartículas , Selênio , Ácido Salicílico/farmacologia , Selênio/farmacologia , Quitosana/farmacologia , Escherichia coli , Staphylococcus aureus , Anti-Infecciosos/farmacologia , Bacillus subtilis , Biofilmes , Pseudomonas aeruginosa
18.
PLoS One ; 19(2): e0298112, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38346040

RESUMO

BACKGROUND: Microbial biofilms, as a hallmark of cystic fibrosis (CF) lung disease and other chronic infections, remain a desirable target for antimicrobial therapy. These biopolymer-based viscoelastic structures protect pathogenic organisms from immune responses and antibiotics. Consequently, treatments directed at disrupting biofilms represent a promising strategy for combating biofilm-associated infections. In CF patients, the viscoelasticity of biofilms is determined mainly by their polymicrobial nature and species-specific traits, such as Pseudomonas aeruginosa filamentous (Pf) bacteriophages. Therefore, we examined the impact of microbicidal ceragenins (CSAs) supported by mucolytic agents-DNase I and poly-aspartic acid (pASP), on the viability and viscoelasticity of mono- and bispecies biofilms formed by Pf-positive and Pf-negative P. aeruginosa strains co-cultured with Staphylococcus aureus or Candida albicans. METHODS: The in vitro antimicrobial activity of ceragenins against P. aeruginosa in mono- and dual-species cultures was assessed by determining minimum inhibitory concentration (MIC) and minimum bactericidal/fungicidal concentration (MBC/MFC). Inhibition of P. aeruginosa mono- and dual-species biofilms formation by ceragenins alone and in combination with DNase I or poly-aspartic acid (pASP) was estimated by the crystal violet assay. Additionally, the viability of the biofilms was measured by colony-forming unit (CFU) counting. Finally, the biofilms' viscoelastic properties characterized by shear storage (G') and loss moduli (G"), were analyzed with a rotational rheometer. RESULTS: Our results demonstrated that ceragenin CSA-13 inhibits biofilm formation and increases its fluidity regardless of the Pf-profile and species composition; however, the Pf-positive biofilms are characterized by elevated viscosity and elasticity parameters. CONCLUSION: Due to its microbicidal and viscoelasticity-modifying properties, CSA-13 displays therapeutic potential in biofilm-associated infections, especially when combined with mucolytic agents.


Assuntos
Anti-Infecciosos , Fibrose Cística , Infecções por Pseudomonas , Esteroides , Humanos , Pseudomonas aeruginosa , Ácido Aspártico , Expectorantes , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Biofilmes , Desoxirribonuclease I , Testes de Sensibilidade Microbiana
19.
Biomed Res Int ; 2024: 4769779, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38347907

RESUMO

Cystic fibrosis (CF) is a genetic disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) that controls chloride current. A number of different CFTR transgenic mouse lines have been developed and subjected to both acute and chronic infection models. However, prior studies showed no substantial differences in bacterial clearance between CF and non-CF mice after single inoculations. Here, using F508del transgenic CF mice, we examined the role of repeated acute Pseudomonas aeruginosa (PA) infection, with the second inoculation 7 days after the first. We found that CF mice were more susceptible to PA infection than non-CF mice following the second inoculation, with non-CF mice showing better neutrophil recruitment and effector functions. We further investigated the characteristics of lung immune cells using single-cell RNA sequencing, finding that non-CF lung neutrophils had more prominent upregulation of adhesion molecules including intercellular adhesion molecule-1 (ICAM-1) compared to CF lung neutrophils. Although people with CF are often colonized with bacteria and have high numbers of neutrophils in the airways during chronic infection, these data suggest that CF neutrophils have deficient effector functions in the setting of repeated acute infection.


Assuntos
Fibrose Cística , Pneumonia , Infecções por Pseudomonas , Humanos , Camundongos , Animais , Fibrose Cística/genética , Fibrose Cística/microbiologia , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Pseudomonas aeruginosa , Infecção Persistente , Pneumonia/complicações , Camundongos Transgênicos , Infecções por Pseudomonas/microbiologia
20.
J Med Microbiol ; 73(2)2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38362900

RESUMO

Pseudomonas aeruginosa is one of the most versatile bacteria with renowned pathogenicity and extensive drug resistance. The diverse habitats of this bacterium include fresh, saline and drainage waters, soil, moist surfaces, taps, showerheads, pipelines, medical implants, nematodes, insects, plants, animals, birds and humans. The arsenal of virulence factors produced by P. aeruginosa includes pyocyanin, rhamnolipids, siderophores, lytic enzymes, toxins and polysaccharides. All these virulent elements coupled with intrinsic, adaptive and acquired antibiotic resistance facilitate persistent colonization and lethal infections in different hosts. To date, treating pulmonary diseases remains complicated due to the chronic secondary infections triggered by hospital-acquired P. aeruginosa. On the contrary, this bacterium can improve plant growth by suppressing phytopathogens and insects. Notably, P. aeruginosa is one of the very few bacteria capable of trans-kingdom transmission and infection. Transfer of P. aeruginosa strains from plant materials to hospital wards, animals to humans, and humans to their pets occurs relatively often. Recently, we have identified that plant-associated P. aeruginosa strains could be pathologically similar to clinical isolates. In this review, we have highlighted the genomic and metabolic factors that facilitate the dominance of P. aeruginosa across different biological kingdoms and the varying roles of this bacterium in plant and human health.


Assuntos
Infecções por Pseudomonas , Pseudomonas aeruginosa , Animais , Humanos , Fatores de Virulência/genética , Virulência/genética , Genômica , Infecções por Pseudomonas/microbiologia
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