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1.
Medicine (Baltimore) ; 103(36): e39462, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39252304

RESUMO

RATIONALE: Infections due to multidrug-resistant (MDR) Pseudomonas aeruginosa are strongly associated with poor outcomes, including prolonged hospitalization and an increased risk of mortality. Antimicrobial options for the treatment of severe infections due to MDR P aeruginosa are quite limited, and treatment remains challenging. PATIENT CONCERNS: A 65-year-old woman presented to our orthopedic clinic with a 3-month history of progressive pain and stiffness in her left knee. Her primary care provider administered a hyaluronic acid injection, which unfortunately resulted in worsening symptoms. Subsequent treatment included a 1-month course of intravenous gentamicin and ceftriaxone, which failed to alleviate her symptoms. DIAGNOSIS: MDR P aeruginosa septic arthritis of the knee. The culture isolate was tested for susceptibility to multiple antibiotics. Magnetic resonance imaging evaluations were conducted, showing notable erosive and osteolytic changes around the joint surfaces that had progressed significantly. INTERVENTIONS: The patient underwent arthroscopic irrigation and synovectomy. The treatment regimen included a combination of intravenous colistin and piperacillin/tazobactam administered over a 6-week period. Total knee arthroplasty was performed 6 months later without additional antibiotic treatment. OUTCOMES: Patient's knee condition remained continuously stable without abnormal findings of inflammation. The patient's knee range of motion increased 0 to 125 degrees, her pain almost disappeared, and she was able to maintain activities of daily life. LESSONS: This case underscores the challenges of managing infections with MDR organisms in complex clinical scenarios, emphasizing the need for timely intervention and appropriate antibiotic therapy.


Assuntos
Antibacterianos , Artrite Infecciosa , Farmacorresistência Bacteriana Múltipla , Infecções por Pseudomonas , Pseudomonas aeruginosa , Humanos , Feminino , Idoso , Artrite Infecciosa/microbiologia , Artrite Infecciosa/tratamento farmacológico , Artrite Infecciosa/diagnóstico , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/isolamento & purificação , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Articulação do Joelho/microbiologia
2.
AAPS PharmSciTech ; 25(7): 203, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39237802

RESUMO

Normal skin is the first line of defense in the human body. A burn injury makes the skin susceptible to bacterial infection, thereby delaying wound healing and ultimately leading to sepsis. The chances of biofilm formation are high in burn wounds due to the presence of avascular necrotic tissue. The most common pathogen to cause burn infection and biofilm is Pseudomonas aeruginosa. The purpose of this study was to create a microemulsion (ME) formulation for topical application to treat bacterial burn infection. In the present study, tea tree oil was used as the oil phase, Tween 80 and transcutol were used as surfactants, and water served as the aqueous phase. Pseudo ternary phase diagrams were used to determine the design space. The ranges of components as suggested by the design were chosen, optimization of the microemulsion was performed, and in vitro drug release was assessed. Based on the characterization studies performed, it was found that the microemulsion were formulated properly, and the particle size obtained was within the desired microemulsion range of 10 to 300 nm. The I release study showed that the microemulsion followed an immediate release profile. The formulation was further tested based on its ability to inhibit biofilm formation and bacterial growth. The prepared microemulsion was capable of inhibiting biofilm formation.


Assuntos
Antibacterianos , Biofilmes , Queimaduras , Sistemas de Liberação de Medicamentos , Emulsões , Pseudomonas aeruginosa , Biofilmes/efeitos dos fármacos , Queimaduras/tratamento farmacológico , Queimaduras/microbiologia , Pseudomonas aeruginosa/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Tamanho da Partícula , Liberação Controlada de Fármacos , Tensoativos/química , Polissorbatos/química , Óleo de Melaleuca/administração & dosagem , Óleo de Melaleuca/química , Óleo de Melaleuca/farmacologia , Química Farmacêutica/métodos , Humanos
3.
Front Cell Infect Microbiol ; 14: 1448104, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39239637

RESUMO

The chronic airway infections with Pseudomonas aeruginosa are the major co-morbidity in people with cystic fibrosis (CF). Within CF lungs, P. aeruginosa persists in the conducting airways together with human mucins as the most abundant structural component of its microenvironment. We investigated the adhesion of 41 serial CF airway P. aeruginosa isolates to airway mucin preparations from CF sputa. Mucins and bacteria were retrieved from five modulator-naïve patients with advanced CF lung disease. The P. aeruginosa isolates from CF airways and non-CF reference strains showed a strain-specific signature in their adhesion to ovine, porcine and bovine submaxillary mucins and CF airway mucins ranging from no or low to moderate and strong binding. Serial CF clonal isolates and colony morphotypes from the same sputum sample were as heterogeneous in their affinity to mucin as representatives of other clones thus making 'mucin binding' one of the most variable intraclonal phenotypic traits of P. aeruginosa known to date. Most P. aeruginosa CF airway isolates did not adhere more strongly to CF airway mucins than to plastic surfaces. The strong binders, however, exhibited a strain-specific affinity gradient to O-glycans, CF airway and mammalian submaxillary mucins.


Assuntos
Aderência Bacteriana , Fibrose Cística , Mucinas , Infecções por Pseudomonas , Pseudomonas aeruginosa , Escarro , Fibrose Cística/microbiologia , Pseudomonas aeruginosa/metabolismo , Pseudomonas aeruginosa/isolamento & purificação , Mucinas/metabolismo , Humanos , Animais , Escarro/microbiologia , Infecções por Pseudomonas/microbiologia , Suínos , Bovinos , Ovinos
4.
Sci Rep ; 14(1): 20715, 2024 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-39237556

RESUMO

Chronic wounds represent a significant global health concern, statistically impacting 1-2% of the population in developed countries throughout their lifetimes. These wounds cause considerable discomfort for patients and necessitate substantial expenditures of time and resources for treatment. Among the emerging therapeutic approaches, medicated dressings incorporating bioactive molecules, including natural compounds, are particularly promising. Hence, the objective of this study was to develop novel antimicrobial dressings for wound treatment. Specifically, polycaprolactone membranes were manufactured using the electrospinning technique and subsequently coated with natural polyelectrolytes (chitosan as a polycation and a mixture of manuka honey with essential oils nanoemulsions as a polyanion) employing the Layer-by-Layer assembly technique. Physico-chemical and morphological characterization was conducted through QCM-D, FTIR-ATR, XPS, and SEM analyses. The results from SEM and QCM-D demonstrated successful layer deposition and coating formation. Furthermore, FTIR-ATR and XPS analyses distinguished among different coating compositions. The coated membranes were tested in the presence of fibroblast cells, demonstrating biocompatibility and expression of genes coding for VEGF, COL1, and TGF-ß1, which are associated with the healing process (assessed through RT-qPCR analysis). Finally, the membranes exhibited excellent antibacterial activity against both Staphylococcus aureus and Pseudomonas aeruginosa, with higher bacterial strain inhibition observed when cinnamon essential oil nanoemulsion was incorporated. Taken together, these results demonstrate the potential application of nanocoated membranes for biomedical applications, such as wound healing.


Assuntos
Mel , Óleos Voláteis , Poliésteres , Cicatrização , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Cicatrização/efeitos dos fármacos , Poliésteres/química , Humanos , Antibacterianos/farmacologia , Antibacterianos/química , Membranas Artificiais , Leptospermum/química , Bandagens , Staphylococcus aureus/efeitos dos fármacos , Quitosana/química , Quitosana/farmacologia , Fibroblastos/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Polieletrólitos/química
5.
Virulence ; 15(1): 2397503, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39282885

RESUMO

Cationic biocides (CBs), which include quaternary ammonium compounds (QACs), are employed to mitigate the spread of infectious bacteria, but resistance to such surface disinfectants is rising. CB exposure can have profound phenotypic implications that extend beyond allowing microorganisms to persist on surfaces. Pseudomonas aeruginosa is a deadly bacterial pathogen that is intrinsically tolerant to a wide variety of antimicrobials and is commonly spread in healthcare settings. In this study, we pursued resistance selection assays to the QAC benzalkonium chloride and quaternary phosphonium compound P6P-10,10 to assess the phenotypic effects of CB exposure in P. aeruginosa PAO1 and four genetically diverse, drug-resistant clinical isolates. In particular, we sought to examine how CB exposure affects defensive strategies and the virulence-associated "offensive" strategies in P. aeruginosa. We demonstrated that development of resistance to BAC is associated with increased production of virulence-associated pigments and alginate as well as pellicle formation. In an in vivo infection model, CB-resistant PAO1 exhibited a decreased level of virulence compared to wild type, potentially due to an observed fitness cost in these strains. Taken together, these results illustrate the significant consequence CB resistance exerts on the virulence-associated phenotypes of P. aeruginosa.


Assuntos
Desinfetantes , Infecções por Pseudomonas , Pseudomonas aeruginosa , Fatores de Virulência , Pseudomonas aeruginosa/patogenicidade , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/genética , Desinfetantes/farmacologia , Virulência , Fatores de Virulência/genética , Infecções por Pseudomonas/microbiologia , Animais , Compostos de Benzalcônio/farmacologia , Farmacorresistência Bacteriana , Camundongos , Compostos de Amônio Quaternário/farmacologia , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Adaptação Fisiológica , Cátions/farmacologia
6.
Proc Natl Acad Sci U S A ; 121(39): e2411981121, 2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-39284057

RESUMO

Bacterial biofilms have been implicated in several chronic infections. After initial attachment, a critical first step in biofilm formation is a cell inducing a surface-sensing response. In the Gram-negative opportunistic pathogen Pseudomonas aeruginosa, two second messengers, cyclic diguanylate monophosphate (c-di-GMP) and cyclic adenosine monophosphate (cAMP), are produced by different surface-sensing mechanisms. However, given the disparate cellular behaviors regulated by these second messengers, how newly attached cells coordinate these pathways remains unclear. Some of the uncertainty relates to studies using different strains, experimental systems, and usually focusing on a single second messenger. In this study, we developed a tricolor reporter system to simultaneously gauge c-di-GMP and cAMP levels in single cells. Using PAO1, we show that c-di-GMP and cAMP are selectively activated in two commonly used experimental systems to study surface sensing. By further examining the conditions that differentiate a c-di-GMP or cAMP response, we demonstrate that an agarose-air interface activates cAMP signaling through type IV pili and the Pil-Chp system. However, a liquid-agarose interface favors the activation of c-di-GMP signaling. This response is dependent on flagellar motility and correlated with higher swimming speed. Collectively, this work indicates that c-di-GMP and cAMP signaling responses are dependent on the surface context.


Assuntos
Biofilmes , AMP Cíclico , GMP Cíclico , Pseudomonas aeruginosa , Pseudomonas aeruginosa/fisiologia , Pseudomonas aeruginosa/metabolismo , GMP Cíclico/metabolismo , GMP Cíclico/análogos & derivados , AMP Cíclico/metabolismo , Biofilmes/crescimento & desenvolvimento , Transdução de Sinais , Sistemas do Segundo Mensageiro/fisiologia , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética
7.
Nat Commun ; 15(1): 8129, 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39285192

RESUMO

When an organism encounters a pathogen, the host innate immune system activates to defend against pathogen colonization and toxic xenobiotics produced. C. elegans employ multiple defense systems to ensure survival when exposed to Pseudomonas aeruginosa including activation of the cytoprotective transcription factor SKN-1/NRF2. Although wildtype C. elegans quickly learn to avoid pathogens, here we describe a peculiar apathy-like behavior towards PA14 in animals with constitutive activation of SKN-1, whereby animals choose not to leave and continue to feed on the pathogen even when a non-pathogenic and healthspan-promoting food option is available. Although lacking the urgency to escape the infectious environment, animals with constitutive SKN-1 activity are not oblivious to the presence of the pathogen and display the typical pathogen-induced intestinal distension and eventual demise. SKN-1 activation, specifically in neurons and intestinal tissues, orchestrates a unique transcriptional program which leads to defects in serotonin signaling that is required from both neurons and non-neuronal tissues. Serotonin depletion from SKN-1 activation limits pathogen defenses capacity, drives the pathogen-associated apathy behaviors and induces a synthetic sensitivity to selective serotonin reuptake inhibitors. Taken together, our work reveals interesting insights into how animals perceive environmental pathogens and subsequently alter behavior and cellular programs to promote survival.


Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Proteínas de Ligação a DNA , Pseudomonas aeruginosa , Serotonina , Fatores de Transcrição , Animais , Caenorhabditis elegans/microbiologia , Caenorhabditis elegans/imunologia , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Pseudomonas aeruginosa/fisiologia , Pseudomonas aeruginosa/patogenicidade , Serotonina/metabolismo , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Neurônios/metabolismo , Infecções por Pseudomonas/imunologia , Infecções por Pseudomonas/metabolismo , Infecções por Pseudomonas/microbiologia , Imunidade Inata , Transdução de Sinais , Apatia/fisiologia , Interações Hospedeiro-Patógeno/imunologia , Inibidores Seletivos de Recaptação de Serotonina/farmacologia
8.
NPJ Biofilms Microbiomes ; 10(1): 82, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39261499

RESUMO

Pseudomonas aeruginosa is a widespread nosocomial pathogen with a significant to cause both severe planktonic acute and biofilm-related chronic infections. Small RNAs (sRNAs) are noncoding regulatory molecules that are stabilized by the RNA chaperone Hfq to trigger various virulence-related signaling pathways. Here, we identified an Hfq-binding sRNA in P. aeruginosa PAO1, PqsS, which promotes bacterial pathogenicity and pseudomonas quinolone signal quorum sensing (pqs QS) system. Specifically, PqsS enhanced acute bacterial infections by inducing host cell death and promoting rhamnolipid-regulated swarming motility. Meanwhile, PqsS reduced chronic infection traits including biofilm formation and antibiotic resistance. Moreover, PqsS repressed pqsL transcript, increasing PQS levels for pqs QS. A PQS-rich environment promoted PqsS expression, thus forming a positive feedback loop. Furthermore, we demonstrated that the PqsS interacts and destabilizes the pqsL mRNA by recruiting RNase E to drive degradation. These findings provide insights for future research on P. aeruginosa pathogenesis and targeted treatment.


Assuntos
Proteínas de Bactérias , Biofilmes , Regulação Bacteriana da Expressão Gênica , Fator Proteico 1 do Hospedeiro , Pseudomonas aeruginosa , Quinolonas , Percepção de Quorum , RNA Bacteriano , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/patogenicidade , Pseudomonas aeruginosa/metabolismo , Virulência , Biofilmes/crescimento & desenvolvimento , Fator Proteico 1 do Hospedeiro/genética , Fator Proteico 1 do Hospedeiro/metabolismo , RNA Bacteriano/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Quinolonas/metabolismo , Quinolonas/farmacologia , Endorribonucleases/metabolismo , Endorribonucleases/genética , Animais , Pequeno RNA não Traduzido/genética , Pequeno RNA não Traduzido/metabolismo , Infecções por Pseudomonas/microbiologia , Humanos , Camundongos , Glicolipídeos/metabolismo
9.
Narra J ; 4(2): e774, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39280309

RESUMO

Infectious wounds on the skin surface are easily colonized by bacteria from pyogenic group that manifest as inflammation, such as Pseudomonas aeruginosa. P. aeruginosa is a Gram-negative bacterium and an opportunistic pathogen known for causing invasive state in critically ill and immunocompromised patients. The aim of this study was to detect the 16S rRNA and gyrB genes in P. aeruginosa using polymerase chain reaction (PCR) method. The sample in this study was pus isolate from a 5-year-old boy with leg wounds. The bacteria were isolated on brain heart infusion broth (BHIB) media and identified with molecular identification. Sequencing and BLAST analysis were carried out to determine the similarity of gene identity by comparing sample sequence with other isolate sequences on the Gene Bank. The results of molecular identification showed amplification DNA band of around 934 base pairs (bp) for 16S rRNA and 225 bp for gyrB gene. The BLAST program demonstrated that the sample had 99.89% similarity with P. aeruginosa strain XC4 (accession code ON795960.1) for the 16S rRNA gene. Meanwhile, the gyrB gene exhibited 99.10% similarity with the P. aeruginosa strain PSA-1.2 (accession code KP172300.1).


Assuntos
DNA Girase , Reação em Cadeia da Polimerase , Infecções por Pseudomonas , Pseudomonas aeruginosa , RNA Ribossômico 16S , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/isolamento & purificação , Masculino , Humanos , RNA Ribossômico 16S/genética , Reação em Cadeia da Polimerase/métodos , Pré-Escolar , Infecções por Pseudomonas/microbiologia , Infecções por Pseudomonas/diagnóstico , DNA Girase/genética , Indonésia , Infecção dos Ferimentos/microbiologia , Infecção dos Ferimentos/diagnóstico , Supuração/microbiologia
10.
Sci Rep ; 14(1): 20523, 2024 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-39227447

RESUMO

A recent scientific investigation has shown promising results of selenium nanoparticles (SeNPs) for the anticancer and antimicrobial activities. This study aims to evaluate the effects of PVP SeNPs on bacterial strains, including Staphylococcus aureus (S. aureus), Bacillus cereus (B. cereus), Klebsiella pneumoniae (K. pneumoniae), Escherichia coli (E. coli), and Pseudomonas aeruginosa (P. aeruginosa). Also, its antitumor activity against the MRC-5 carcinoma cell line. SeNPs were prepared via gamma irradiation using PVP as a capping agent, and their size and morphological structure were determined using HRTEM. The size of the SeNPs ranged from 36 to 66.59 nm. UV-vis spectra confirmed the formation of SeNPs, while FTIR measurement confirmed a change in the PVP structure after adding selenium nanoparticles. The highest effect was reported on HepG2 by an IC50 with a value of 8.87 µg/ml, followed by HeLa, PC3, MCF-7, and Caco2 cell lines, respectively. Furthermore, ZOI reached 36.33 ± 3.05 mm. The best value of the minimum inhibitory concentration (MIC) was 0.313 µg/ml. Scanning electron microscope (SEM) imaging against bacteria showed deformations and distortions in their structures. Transmission electron (TEM) revealed ultrastructure changes in treated bacteria because of the free radicals that made cytotoxicity which confirmed by Electron spin resonance (ESR).


Assuntos
Antibacterianos , Raios gama , Testes de Sensibilidade Microbiana , Selênio , Humanos , Antibacterianos/farmacologia , Antibacterianos/química , Selênio/química , Selênio/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/química , Linhagem Celular Tumoral , Bactérias/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Bacillus cereus/efeitos dos fármacos , Nanopartículas/química , Pseudomonas aeruginosa/efeitos dos fármacos
11.
Nat Microbiol ; 9(9): 2308-2322, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39227714

RESUMO

Swimming bacteria navigate chemical gradients using temporal sensing to detect changes in concentration over time. Here we show that surface-attached bacteria use a fundamentally different mode of sensing during chemotaxis. We combined microfluidic experiments, massively parallel cell tracking and fluorescent reporters to study how Pseudomonas aeruginosa senses chemical gradients during pili-based 'twitching' chemotaxis on surfaces. Unlike swimming cells, we found that temporal changes in concentration did not induce motility changes in twitching cells. We then quantified the chemotactic behaviour of stationary cells by following changes in the sub-cellular localization of fluorescent proteins as cells are exposed to a gradient that alternates direction. These experiments revealed that P. aeruginosa cells can directly sense differences in concentration across the lengths of their bodies, even in the presence of strong temporal fluctuations. Our work thus overturns the widely held notion that bacterial cells are too small to directly sense chemical gradients in space.


Assuntos
Quimiotaxia , Pseudomonas aeruginosa , Pseudomonas aeruginosa/fisiologia , Fímbrias Bacterianas/metabolismo , Microfluídica/métodos , Proteínas Luminescentes/metabolismo , Proteínas Luminescentes/genética
12.
BMC Infect Dis ; 24(1): 911, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39227823

RESUMO

BACKGROUND: The 2016 IDSA guideline recommends a treatment duration of at least 7 days for hospital-acquired (HAP)/ventilator-associated pneumonia (VAP). The limited literature has demonstrated higher rates of recurrence for non-glucose fermenting gram-negative bacilli with short course therapy, raising the concern of optimal treatment duration for these pathogens. Therefore, we aimed to compare the outcomes for patients receiving shorter therapy treatment (≤ 8 days) versus longer regimen (> 8 days) for the treatment of multidrug resistant (MDR) Pseudomonas pneumonia. METHODS: A single-center, retrospective cohort study was conducted to evaluate adult patients receiving an antimicrobial regimen with activity against MDR Pseudomonas aeruginosa in respiratory culture between 2017 and 2020 for a minimum of 6 consecutive days. Exclusion criteria were inmates, those with polymicrobial pneumonia, community-acquired pneumonia, and infections requiring prolonged antibiotic therapy. RESULTS: Of 427 patients with MDR P. aeruginosa respiratory isolates, 85 patients were included. Baseline characteristics were similar among groups with a median age of 65.5 years and median APACHE 2 score of 20. Roughly 75% had ventilator-associated pneumonia. Compared to those who received ≤ 8 days of therapy, no difference was seen for clinical success in patients treated for more than 8 days (80% vs. 65.5%, p = 0.16). The number of 30-day and 90-day in-hospital mortality, 30-days relapse, and other secondary outcomes did not significantly differ among the treatment groups. CONCLUSIONS: Prolonging treatment duration beyond 8 days did not improve patient outcomes for MDR P. aeruginosa HAP/VAP.


Assuntos
Antibacterianos , Farmacorresistência Bacteriana Múltipla , Infecções por Pseudomonas , Pseudomonas aeruginosa , Humanos , Masculino , Feminino , Pseudomonas aeruginosa/efeitos dos fármacos , Estudos Retrospectivos , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Idoso , Pessoa de Meia-Idade , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Infecções por Pseudomonas/mortalidade , Pneumonia Associada à Ventilação Mecânica/tratamento farmacológico , Pneumonia Associada à Ventilação Mecânica/microbiologia , Pneumonia Associada à Ventilação Mecânica/mortalidade , Resultado do Tratamento , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Bacteriana/microbiologia , Pneumonia Bacteriana/mortalidade , Duração da Terapia
13.
Nat Commun ; 15(1): 7927, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39256376

RESUMO

Detecting chemical signals is important for identifying food sources and avoiding harmful agents. Like many animals, C. elegans use olfaction to chemotax towards their main food source, bacteria. However, little is known about the bacterial compounds governing C. elegans attraction to bacteria and the physiological importance of these compounds to bacteria. Here, we address these questions by investigating the function of a small RNA, P11, in the pathogen, Pseudomonas aeruginosa, that was previously shown to mediate learned pathogen avoidance. We discovered that this RNA also affects the attraction of untrained C. elegans to P. aeruginosa and does so by controlling production of ammonia, a volatile odorant produced during nitrogen assimilation. We describe the complex regulation of P. aeruginosa nitrogen assimilation, which is mediated by a partner-switching mechanism involving environmental nitrates, sensor proteins, and P11. In addition to mediating C. elegans attraction, we demonstrate that nitrogen assimilation mutants perturb bacterial fitness and pathogenesis during C. elegans infection by P. aeruginosa. These studies define ammonia as a major mediator of trans-kingdom signaling, implicate nitrogen assimilation as important for both bacteria and host organisms, and highlight how a bacterial metabolic pathway can either benefit or harm a host in different contexts.


Assuntos
Amônia , Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Nitrogênio , Pseudomonas aeruginosa , Caenorhabditis elegans/microbiologia , Caenorhabditis elegans/metabolismo , Pseudomonas aeruginosa/metabolismo , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/fisiologia , Animais , Nitrogênio/metabolismo , Amônia/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Infecções por Pseudomonas/microbiologia , Infecções por Pseudomonas/metabolismo , Nitratos/metabolismo , Transdução de Sinais , Interações Hospedeiro-Patógeno , Quimiotaxia
14.
Elife ; 132024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39269443

RESUMO

How bacterial pathogens exploit host metabolism to promote immune tolerance and persist in infected hosts remains elusive. To achieve this, we show that Pseudomonas aeruginosa (PA), a recalcitrant pathogen, utilizes the quorum sensing (QS) signal 2'-aminoacetophenone (2-AA). Here, we unveil how 2-AA-driven immune tolerization causes distinct metabolic perturbations in murine macrophages' mitochondrial respiration and bioenergetics. We present evidence indicating that these effects stem from decreased pyruvate transport into mitochondria. This reduction is attributed to decreased expression of the mitochondrial pyruvate carrier (Mpc1), which is mediated by diminished expression and nuclear presence of its transcriptional regulator, estrogen-related nuclear receptor alpha (Esrra). Consequently, Esrra exhibits weakened binding to the Mpc1 promoter. This outcome arises from the impaired interaction between Esrra and the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Ppargc1a). Ultimately, this cascade results in diminished pyruvate influx into mitochondria and, consequently reduced ATP production in tolerized murine and human macrophages. Exogenously added ATP in infected macrophages restores the transcript levels of Mpc1 and Esrra and enhances cytokine production and intracellular bacterial clearance. Consistent with the in vitro findings, murine infection studies corroborate the 2-AA-mediated long-lasting decrease in ATP and acetyl-CoA and its association with PA persistence, further supporting this QS signaling molecule as the culprit of the host bioenergetic alterations and PA persistence. These findings unveil 2-AA as a modulator of cellular immunometabolism and reveal an unprecedented mechanism of host tolerance to infection involving the Ppargc1a/Esrra axis in its influence on Mpc1/OXPHOS-dependent energy production and PA clearance. These paradigmatic findings pave the way for developing treatments to bolster host resilience to pathogen-induced damage. Given that QS is a common characteristic of prokaryotes, it is likely that 2-AA-like molecules with similar functions may be present in other pathogens.


Assuntos
Metabolismo Energético , Macrófagos , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Pseudomonas aeruginosa , Percepção de Quorum , Animais , Camundongos , Pseudomonas aeruginosa/fisiologia , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Macrófagos/metabolismo , Macrófagos/microbiologia , Macrófagos/imunologia , Infecções por Pseudomonas/imunologia , Infecções por Pseudomonas/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Estrogênio/genética , Tolerância Imunológica , Mitocôndrias/metabolismo , Humanos , Acetofenonas/farmacologia , Acetofenonas/metabolismo
15.
Int J Mol Sci ; 25(17)2024 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-39273327

RESUMO

Periodontitis is a chronic inflammatory disease resulting from the dysbiosis of periodontal bacteria and the host's immune response, leading to tissue degradation and sustained inflammation. Traditional treatments, such as mechanical debridement and antimicrobial agents, often fail to fully eradicate pathogenic bacteria, especially in deep periodontal pockets. Consequently, the need for novel therapeutic approaches has increased the interest in bioactive natural extracts, such as that of Opuntia ficus-indica, known for its anti-inflammatory, antioxidant, and antimicrobial properties. This study investigates the encapsulation of Opuntia ficus-indica extract in OFI-loaded chitosan nanoparticles (OFI-NPs) via ionotropic gelation using a microfluidic system, allowing precise control over nanoparticle characteristics and enhancing protection against enzymatic degradation. To achieve localized and sustained release in periodontal pockets, a thermo-responsive hydrogel comprising hyaluronic acid and Pluronic F127 (OFI@tgels) was developed. The transition of OFI@tgels from a solution at low temperatures to a solid at body temperature enables prolonged drug release at inflammation sites. The in vitro application of the optimized formulation eradicated biofilms of S. mutans, P. aeruginosa (PAO1), and P. gingivalis over 36 h and disrupted extracellular polymeric substance formation. Additionally, OFI@tgel modulated immune responses by inhibiting M1 macrophage polarization and promoting a shift to the M2 phenotype. These findings suggest that OFI@tgel is a promising alternative treatment for periodontitis, effectively reducing biofilm formation and modulating the immune response.


Assuntos
Quitosana , Hidrogéis , Nanopartículas , Opuntia , Periodontite , Extratos Vegetais , Quitosana/química , Opuntia/química , Nanopartículas/química , Periodontite/tratamento farmacológico , Periodontite/microbiologia , Periodontite/terapia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Hidrogéis/química , Animais , Camundongos , Antibacterianos/farmacologia , Antibacterianos/química , Streptococcus mutans/efeitos dos fármacos , Humanos , Biofilmes/efeitos dos fármacos , Porphyromonas gingivalis/efeitos dos fármacos , Liberação Controlada de Fármacos , Portadores de Fármacos/química , Poloxâmero/química , Pseudomonas aeruginosa/efeitos dos fármacos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química
16.
Molecules ; 29(17)2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39275040

RESUMO

Graphitic carbon nitride (g-C3N4, CN) has emerged as a promising photocatalytic material due to its inherent stability, antibacterial properties, and eco-friendliness. However, its tendency to aggregate and limited dispersion hinder its efficacy in practical antibacterial applications. To address these limitations, this study focuses on developing a composite hydrogel coating, in which sodium alginate (SA) molecules interact electrostatically and through hydrogen bonding to anchor CN, thereby significantly improving its dispersion. The optimal CN loading of 35% results in a hydrogel with a tensile strength of 120 MPa and an antibacterial rate of 99.87% within 6 h. The enhanced mechanical properties are attributed to hydrogen bonding between the -NH2 groups of CN and the -OH groups of SA, while the -OH groups of SA facilitate the attraction of photogenerated holes from CN, promoting carrier transfer and separation, thereby strengthening the antibacterial action. Moreover, the hydrogel coating exhibits excellent antibacterial and corrosion resistance capabilities against Pseudomonas aeruginosa on 316L stainless steel (316L SS), laying the foundation for advanced antimicrobial and anticorrosion hydrogel systems.


Assuntos
Alginatos , Antibacterianos , Grafite , Hidrogéis , Pseudomonas aeruginosa , Alginatos/química , Antibacterianos/farmacologia , Antibacterianos/química , Pseudomonas aeruginosa/efeitos dos fármacos , Hidrogéis/química , Hidrogéis/farmacologia , Grafite/química , Grafite/farmacologia , Compostos de Nitrogênio/química , Compostos de Nitrogênio/farmacologia , Corrosão , Testes de Sensibilidade Microbiana , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Ligação de Hidrogênio , Aço Inoxidável/química
17.
J Photochem Photobiol B ; 259: 113023, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39241393

RESUMO

Pseudomonas aeruginosa, a notable pathogen frequently associated with hospital-acquired infections, displays diverse intrinsic and acquired antibiotic resistance mechanisms, posing a significant challenge in infection management. Antimicrobial blue light (aBL) has been demonstrated as a potential alternative for treating P. aeruginosa infections. In this study, we investigated the impact of blue light wavelength, bacterial growth stage, and growth medium composition on the efficacy of aBL. First, we compared the efficacy of light wavelengths 405 nm, 415 nm, and 470 nm in killing three multidrug resistant clinical strains of P. aeruginosa. The findings indicated considerably higher antibacterial efficacy for 405 nm and 415 nm wavelength compared to 470 nm. We then evaluated the impact of the bacterial growth stage on the efficacy of 405 nm light in killing P. aeruginosa using a reference strain PAO1 in exponential, transitional, or stationary phase. We found that bacteria in the exponential phase were the most susceptible to aBL, followed by the transitional phase, while those in the stationary phase exhibited the highest tolerance. Additionally, we quantified the production of reactive oxygen species (ROS) in bacteria using the 2',7'-dichlorofluorescein diacetate (DCFH-DA) probe and flow cytometry, and observed a positive correlation between aBL efficacy and ROS production. Finally, we determined the influence of growth medium on aBL efficacy. PAO1 was cultivated in brain heart infusion (BHI), Luria-Bertani (LB) broth or Casamino acids (CAA) medium, before being irradiated with aBL at 405 nm. The CAA-grown bacteria exhibited the highest sensitivity to aBL, followed by those grown in LB broth, and the BHI-grown bacteria demonstrated the lowest sensitivity. By incorporating FeCl3, MnCl2, ZnCl2, or the iron chelator 2,2'-bipyridine (BIP) into specific media, we discovered that aBL efficacy was affected by the iron levels in culture media.


Assuntos
Meios de Cultura , Luz , Pseudomonas aeruginosa , Espécies Reativas de Oxigênio , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos da radiação , Espécies Reativas de Oxigênio/metabolismo , Meios de Cultura/química , Antibacterianos/farmacologia , Antibacterianos/química , Testes de Sensibilidade Microbiana , Luz Azul
18.
Arch Microbiol ; 206(10): 402, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39261342

RESUMO

A global water crisis is emerging due to increasing levels of contaminated water and decreasing clean water supply on Earth. This study aims to address the removal of azo dye from wastewater to enable its reuse. Recently, utilizing microorganisms has been proven to be a practical choice for the remediation of azo dyes in wastewater. Hence, in this study, we employed a preformed biofilm of Pseudomonas aeruginosa on a solid support (called substrate) to degrade azo dyes. This process offers several advantages, such as stability, substrate portability, more biofilm production in less time, and efficient utilization of enzymes for remediation. From 50 ppm of initial Congo Red concentration, 75.74% decolorization was achieved within ten h using a preformed biofilm on a coverslip. A maximum of 52.27% decolorization was achieved using biofilm during its formation after 72 h of incubation. The Fourier-transform infrared (FTIR) spectroscopic analysis of Congo Red dye before and after remediation revealed a significant change in peak intensity, indicating dye degradation. Phytotoxicity studies performed by seed germination with Vigna radiata revealed that, after 5-7 days, almost 40% more seeds with longer root and shoot lengths were germinated in the presence of treated dye compared to the untreated one. This data indicated that the harmful Congo Red was successfully degraded to a non-toxic product by Pseudomonas aeruginosa biofilm grown on a glass substrate.


Assuntos
Biodegradação Ambiental , Biofilmes , Vermelho Congo , Pseudomonas aeruginosa , Biofilmes/crescimento & desenvolvimento , Vermelho Congo/metabolismo , Pseudomonas aeruginosa/fisiologia , Pseudomonas aeruginosa/metabolismo , Águas Residuárias/microbiologia , Poluentes Químicos da Água/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier , Corantes/metabolismo , Germinação
19.
Sci Rep ; 14(1): 21006, 2024 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-39251613

RESUMO

The emission of glyphosate and antibiotic residues from human activities threatens the diversity and functioning of the microbial community. This study examines the impact of a glyphosate-based herbicide (GBH) and common antibiotics on Gram-negative bacteria within the ESKAPEE group (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp. and Escherichia coli). Ten strains, including type and multidrug-resistant strains for each species were analysed and eight antibiotics (cefotaxime, meropenem, aztreonam, ciprofloxacin, gentamicin, tigecycline, sulfamethoxazole-trimethoprim, and colistin) were combined with the GBH. While most combinations yielded additive or indifferent effects in 70 associations, antagonistic effects were observed with ciprofloxacin and gentamicin in five strains. GBH notably decreased the minimum inhibitory concentration of colistin in eight strains and displayed synergistic activity with meropenem against metallo-ß-lactamase (MBL)-producing strains. Investigation into the effect of GBH properties on outer membrane permeability involved exposing strains to a combination of this GBH and vancomycin. Results indicated that GBH rendered strains sensitive to vancomycin, which is typically ineffective against Gram-negative bacteria. Furthermore, we examined the impact of GBH in combination with three carbapenem agents on 14 strains exhibiting varying carbapenem-resistance mechanisms to assess its effect on carbapenemase activity. The GBH efficiently inhibited MBL activity, demonstrating similar effects to EDTA (ethylenediaminetetraacetic acid). Chelating effect of GBH may have multifaceted impacts on bacterial cells, potentially by increasing outer membrane permeability and inactivating metalloenzyme activity.


Assuntos
Acinetobacter baumannii , Antibacterianos , Glicina , Glifosato , Bactérias Gram-Negativas , Herbicidas , Testes de Sensibilidade Microbiana , Glicina/análogos & derivados , Glicina/farmacologia , Antibacterianos/farmacologia , Herbicidas/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Acinetobacter baumannii/efeitos dos fármacos , Klebsiella pneumoniae/efeitos dos fármacos , Humanos , Escherichia coli/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Ciprofloxacina/farmacologia , Enterococcus faecium/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Colistina/farmacologia , Vancomicina/farmacologia , Enterobacter/efeitos dos fármacos , Sinergismo Farmacológico , Meropeném/farmacologia , Fenótipo , Gentamicinas/farmacologia
20.
Sci Rep ; 14(1): 20894, 2024 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-39245771

RESUMO

This study proposes an innovative approach to combat the escalating threat of antibiotic resistance in bacteria by introducing a novel ZnO-propolis nanocomposite (ZnO-P NCs). The overuse of antibiotics, particularly during events like the COVID-19 pandemic, has intensified bacterial resistance, necessitating innovative solutions. The study employs a cost-effective and controllable biosynthesis method to produce ZnO nanoparticles (ZnO-NPs), with propolis extract crucially contributing to the reduction and stabilization of Zn2+ ions. A biodegradable nano-propolis matrix is then created by incorporating ZnO-NPs, forming the ZnO-P NCs. Structural stability is confirmed through FT-IR and Zeta potential analysis, while nanoscale properties are validated via TEM, SEM, and XRD analyses. The antimicrobial efficacy of various substances, including propolis, nano propolis, ethanolic propolis extract, ZnO-NPs, and ZnO-P NCs, is assessed against Gram-negative and Gram-positive bacteria, alongside a comparison with 28 antibiotics. Among the bacteria tested, Pseudomonas aeruginosa PAO1 ATCC15692 was more sensitive (40 mm) to the biosynthesized nanocomposite ZnO-P NCs than to ZnO-NPs (38 mm) and nanopropolis (32 mm), while Escherichia coli was resistant to nanopropolis (0 mm) than to ZnO-NPs (31 mm), and ZnO-P NCs (34 mm). The study reveals a synergy effect when combining propolis with green-synthesized ZnO-NPs in the form of ZnO-P NCs, significantly improving their efficiency against all tested bacteria, including antibiotic-resistant strains like E. coli. The nanocomposite outperforms other materials and antibiotics, demonstrating remarkable antibacterial effectiveness. SEM imaging confirms the disruption of bacterial cell membranes by ZnO-NPs and ZnO-P NCs. The study emphasizes the potential applications of ZnO-NPs integrated into biodegradable materials and underscores the significance of the zinc oxide-propolis nanocomposite in countering antimicrobial resistance. Overall, this research offers a comprehensive solution to combat multidrug-resistant bacteria, opening avenues for novel approaches in infection control.


Assuntos
Antibacterianos , Testes de Sensibilidade Microbiana , Nanocompostos , Própole , Óxido de Zinco , Óxido de Zinco/química , Óxido de Zinco/farmacologia , Própole/química , Própole/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Nanocompostos/química , Pseudomonas aeruginosa/efeitos dos fármacos , Farmacorresistência Bacteriana/efeitos dos fármacos , Humanos , Espectroscopia de Infravermelho com Transformada de Fourier , Nanopartículas Metálicas/química
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