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1.
J Orthop Surg Res ; 19(1): 304, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38769535

RESUMO

BACKGROUND: Periprosthetic joint infection is a serious complication following joint replacement. The development of bacterial biofilms bestows antibiotic resistance and restricts treatment via implant retention surgery. Electromagnetic induction heating is a novel technique for antibacterial treatment of metallic surfaces that has demonstrated in-vitro efficacy. Previous studies have always employed stationary, non-portable devices. This study aims to assess the in-vitro efficacy of induction-heating disinfection of metallic surfaces using a new Portable Disinfection System based on Induction Heating. METHODS: Mature biofilms of three bacterial species: S. epidermidis ATCC 35,984, S. aureus ATCC 25,923, E. coli ATCC 25,922, were grown on 18 × 2 mm cylindrical coupons of Titanium-Aluminium-Vanadium (Ti6Al4V) or Cobalt-chromium-molybdenum (CoCrMo) alloys. Study intervention was induction-heating of the coupon surface up to 70ºC for 210s, performed using the Portable Disinfection System (PDSIH). Temperature was monitored using thermographic imaging. For each bacterial strain and each metallic alloy, experiments and controls were conducted in triplicate. Bacterial load was quantified through scraping and drop plate techniques. Data were evaluated using non-parametric Mann-Whitney U test for 2 group comparison. Statistical significance was fixed at p ≤ 0.05. RESULTS: All bacterial strains showed a statistically significant reduction of CFU per surface area in both materials. Bacterial load reduction amounted to 0.507 and 0.602 Log10 CFU/mL for S. aureus on Ti6Al4V and CoCrMo respectively, 5.937 and 3.500 Log10 CFU/mL for E. coli, and 1.222 and 0.372 Log10 CFU/mL for S. epidermidis. CONCLUSIONS: Electromagnetic induction heating using PDSIH is efficacious to reduce mature biofilms of S aureus, E coli and S epidermidis growing on metallic surfaces of Ti6Al4V and CoCrMo alloys.


Assuntos
Ligas , Biofilmes , Desinfecção , Escherichia coli , Infecções Relacionadas à Prótese , Staphylococcus aureus , Titânio , Biofilmes/efeitos dos fármacos , Desinfecção/métodos , Escherichia coli/crescimento & desenvolvimento , Staphylococcus aureus/efeitos dos fármacos , Infecções Relacionadas à Prótese/prevenção & controle , Infecções Relacionadas à Prótese/microbiologia , Staphylococcus epidermidis/efeitos dos fármacos , Prótese Articular/microbiologia , Artroplastia de Substituição/instrumentação , Artroplastia de Substituição/métodos , Calefação/instrumentação , Calefação/métodos , Humanos , Fenômenos Eletromagnéticos , Vitálio
2.
Ann Clin Microbiol Antimicrob ; 23(1): 44, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38755634

RESUMO

BACKGROUND: Due to their resistance and difficulty in treatment, biofilm-associated infections are problematic among hospitalized patients globally and account for 60% of all bacterial infections in humans. Antibiofilm peptides have recently emerged as an alternative treatment since they can be effectively designed and exert a different mode of biofilm inhibition and eradication. METHODS: A novel antibiofilm peptide, BiF, was designed from the conserved sequence of 18 α-helical antibiofilm peptides by template-assisted technique and its activity was improved by hybridization with a lipid binding motif (KILRR). Novel antibiofilm peptide derivatives were modified by substituting hydrophobic amino acids at positions 5 or 7, and both, with positively charged lysines (L5K, L7K). These peptide derivatives were tested for antibiofilm and antimicrobial activities against biofilm-forming Staphylococcus epidermidis and multiple other microbes using crystal violet and broth microdilution assays, respectively. To assess their impact on mammalian cells, the toxicity of peptides was determined through hemolysis and cytotoxicity assays. The stability of candidate peptide, BiF2_5K7K, was assessed in human serum and its secondary structure in bacterial membrane-like environments was analyzed using circular dichroism. The action of BiF2_5K7K on planktonic S. epidermidis and its effect on biofilm cell viability were assessed via viable counting assays. Its biofilm inhibition mechanism was investigated through confocal laser scanning microscopy and transcription analysis. Additionally, its ability to eradicate mature biofilms was examined using colony counting. Finally, a preliminary evaluation involved coating a catheter with BiF2_5K7K to assess its preventive efficacy against S. epidermidis biofilm formation on the catheter and its surrounding area. RESULTS: BiF2_5K7K, the modified antibiofilm peptide, exhibited dose-dependent antibiofilm activity against S. epidermidis. It inhibited biofilm formation at subinhibitory concentrations by altering S. epidermidis extracellular polysaccharide production and quorum-sensing gene expression. Additionally, it exhibited broad-spectrum antimicrobial activity and no significant hemolysis or toxicity against mammalian cell lines was observed. Its activity is retained when exposed to human serum. In bacterial membrane-like environments, this peptide formed an α-helix amphipathic structure. Within 4 h, a reduction in the number of S. epidermidis colonies was observed, demonstrating the fast action of this peptide. As a preliminary test, a BiF2_5K7K-coated catheter was able to prevent the development of S. epidermidis biofilm both on the catheter surface and in its surrounding area. CONCLUSIONS: Due to the safety and effectiveness of BiF2_5K7K, we suggest that this peptide be further developed to combat biofilm infections, particularly those of biofilm-forming S. epidermidis.


Assuntos
Antibacterianos , Biofilmes , Testes de Sensibilidade Microbiana , Staphylococcus epidermidis , Biofilmes/efeitos dos fármacos , Staphylococcus epidermidis/efeitos dos fármacos , Staphylococcus epidermidis/fisiologia , Humanos , Antibacterianos/farmacologia , Antibacterianos/química , Hemólise/efeitos dos fármacos , Peptídeos Antimicrobianos/farmacologia , Peptídeos Antimicrobianos/química , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia
3.
Iran J Med Sci ; 49(5): 332-338, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38751870

RESUMO

The present study aimed to investigate secondary bacterial infections among patients infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Coagulase-negative Staphylococci can infect immunocompromised patients. Linezolid resistance among Staphylococcus epidermidis is one of the most critical issues. In 2019, 185 SARS-CoV-2-positive patients who were admitted to North Khorasan Province Hospital (Bojnurd, Iran), were investigated. Patients having positive SARS-CoV-2 reverse transcriptase real-time polymerase chain reaction (RT-PCR) test results, who had a history of intubation, mechanical ventilation, and were hospitalized for more than 48 hours were included. After microbiological evaluation of pulmonary samples, taken from intubated patients with clinical manifestation of pneumonia, co-infections were found in 11/185 patients (5.94%) with S. epidermidis, Staphylococcus aureus, and Acinetobacter baumani, respectively. Remarkably, seven out of nine S. epidermidis isolates were linezolid resistant. Selected isolates were characterized using antimicrobial resistance patterns and molecular methods, such as Staphylococcal cassette chromosome mec (SCCmec) typing, and gene detection for ica, methicillin resistance (mecA), vancomycin resistance (vanA), and chloramphenicol-florfenicol resistance (cfr) genes. All of the isolates were resistant to methicillin, and seven isolates were resistant to linezolid. Nine out of 11 isolated belonged to the SCCmec I, while two belonged to the SCCmec IV. It should be noted that all patients had the underlying disease, and six patients had already passed away. The increasing linezolid resistance in bacterial strains becomes a real threat to patients, and monitoring such infections, in conjunction with surveillance and infection prevention programs, is very critical for reducing the number of linezolid-resistant Staphylococcal strains. A preprint of this study was published at https://europepmc.org/article/ppr/ppr417742.


Assuntos
COVID-19 , Linezolida , Infecções Estafilocócicas , Staphylococcus epidermidis , Humanos , Linezolida/farmacologia , Linezolida/uso terapêutico , Staphylococcus epidermidis/efeitos dos fármacos , Irã (Geográfico)/epidemiologia , COVID-19/epidemiologia , Masculino , Feminino , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/epidemiologia , Pessoa de Meia-Idade , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Idoso , Coinfecção/epidemiologia , Coinfecção/tratamento farmacológico , Coinfecção/microbiologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Adulto , SARS-CoV-2 , Testes de Sensibilidade Microbiana/métodos
4.
Int J Mol Sci ; 25(9)2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38732057

RESUMO

Implant therapy is a common treatment option in dentistry and orthopedics, but its application is often associated with an increased risk of microbial contamination of the implant surfaces that cause bone tissue impairment. This study aims to develop two silver-enriched platelet-rich plasma (PRP) multifunctional scaffolds active at the same time in preventing implant-associated infections and stimulating bone regeneration. Commercial silver lactate (L) and newly synthesized silver deoxycholate:ß-Cyclodextrin (B), were studied in vitro. Initially, the antimicrobial activity of the two silver soluble forms and the PRP enriched with the two silver forms has been studied on microbial planktonic cells. At the same time, the biocompatibility of silver-enriched PRPs has been assessed by an MTT test on human primary osteoblasts (hOBs). Afterwards, an investigation was conducted to evaluate the activity of selected concentrations and forms of silver-enriched PRPs in inhibiting microbial biofilm formation and stimulating hOB differentiation. PRP-L (0.3 µg/mm2) and PRP-B (0.2 µg/mm2) counteract Staphylococcus aureus, Staphylococcus epidermidis and Candida albicans planktonic cell growth and biofilm formation, preserving hOB viability without interfering with their differentiation capability. Overall, the results obtained suggest that L- and B-enriched PRPs represent a promising preventive strategy against biofilm-related implant infections and demonstrate a new silver formulation that, together with increasing fibrin binding protecting silver in truncated cone-shaped cyclic oligosaccharides, achieved comparable inhibitory results on prokaryotic cells at a lower concentration.


Assuntos
Biofilmes , Osteoblastos , Plasma Rico em Plaquetas , Prata , Humanos , Biofilmes/efeitos dos fármacos , Prata/química , Prata/farmacologia , Osteoblastos/efeitos dos fármacos , Osteoblastos/citologia , Staphylococcus aureus/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Infecções Relacionadas à Prótese/prevenção & controle , Infecções Relacionadas à Prótese/microbiologia , Staphylococcus epidermidis/efeitos dos fármacos
5.
Mar Drugs ; 22(4)2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38667771

RESUMO

Algae are used as safe materials to fabricate novel nanoparticles to treat some diseases. Marine brown alga Sargassum vulgare are used to fabricate silver nanoparticles (Sv/Ag-NPs). The characterization of Sv/Ag-NPs was determined by TEM, EDX, Zeta potential, XRD, and UV spectroscopy. The Sv/Ag-NPs were investigated as antioxidant, anticancer, and antibacterial activities against Gram-positive bacteria Bacillus mojavensis PP400982, Staphylococcus caprae PP401704, Staphylococcus capitis PP402689, and Staphylococcus epidermidis PP403851. The activity of the Sv/Ag-NPs was evaluated as hepatoprotective in vitro in comparison with silymarin. The UV-visible spectrum of Sv/Ag-NPs appeared at 442 nm; the size of Sv/Ag-NPs is in range between 6.90 to 16.97 nm, and spherical in shape. Different concentrations of Sv/Ag-NPs possessed antioxidant, anticancer activities against (HepG-2), colon carcinoma (HCT-116), cervical carcinoma (HeLa), and prostate carcinoma (PC-3) with IC50 50.46, 45.84, 78.42, and 100.39 µg/mL, respectively. The Sv/Ag-NPs induced the cell viability of Hep G2 cells and hepatocytes treated with carbon tetrachloride. The Sv/Ag-NPs exhibited antibacterial activities against Staphylococcus caprae PP401704, Staphylococcus capitis PP402689, and Staphylococcus epidermidis PP403851. This study strongly suggests the silver nanoparticles derived from Sargassum vulgare showed potential hepato-protective effect against carbon tetrachloride-induced liver cells, and could be used as anticancer and antibacterial activities.


Assuntos
Antibacterianos , Antineoplásicos , Antioxidantes , Nanopartículas Metálicas , Sargassum , Prata , Antibacterianos/farmacologia , Antibacterianos/química , Humanos , Prata/farmacologia , Prata/química , Antioxidantes/farmacologia , Antioxidantes/química , Nanopartículas Metálicas/química , Sargassum/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Linhagem Celular Tumoral , Testes de Sensibilidade Microbiana , Células Hep G2 , Substâncias Protetoras/farmacologia , Substâncias Protetoras/química , Staphylococcus epidermidis/efeitos dos fármacos , Células HeLa
6.
Sci Rep ; 14(1): 9183, 2024 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-38649676

RESUMO

Staphylococci as a nosocomial infection agent, increases the possibility of contracting diseases such as wound infection, sepsis and skin infections in humans. It was shown that Staphylococcus aureus considered as a commensal organism causing various both endemic and epidemic hospital-acquired infections. Air samples were collected from Sina Hospital, Hamadan city, which dedicated to various respiratory diseases and analysed by biochemical tests. The resistance and sensitivity of bacterial strains to the cefoxitin antibiotic were also determined. Staphylococcus aureus density (CFU/m3) were measured in the air of various wards as follows: infectious 13.35 ± 7.57, poisoning 29.84 ± 33.43, emergency 8.64 ± 2.72, eye operation room 0, recovery room 6.28 ± 4.90, skin outpatient operation room 4.71 ± 2.36, respiratory isolation 0, ICU 0.79 ± 1.36, and the administrative room 6.28 ± 5.93; while the Staphylococcus epidermidis were as follows: infectious 1.57 ± 2.35, poisoning 2.35 ± 4.08, emergency 2.35 ± 2.35, eye operation room 0, recovery room 0.78 ± 1.36, skin outpatient operation room 2.35 ± 2.35, respiratory isolation 0, ICU 2.35 ± 4.08, and the administrative room 1.57 ± 1.36. The positive and negative control samples showed a concentration of 0. Moreover, among the S. aureus isolates, 33.3% were found to be resistant to cefoxitin, while 40.6% showed to be sensitive. Based on the results, the number of active people and the type and quality of ventilation are very effective in the air quality of various wards of hospital. The poisoning section showed the most contaminated air and the highest resistance and sensitivity to the cefoxitin antibiotic.


Assuntos
Microbiologia do Ar , Antibacterianos , Cefoxitina , Hospitais , Testes de Sensibilidade Microbiana , Staphylococcus aureus , Staphylococcus epidermidis , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/isolamento & purificação , Staphylococcus epidermidis/efeitos dos fármacos , Staphylococcus epidermidis/isolamento & purificação , Cefoxitina/farmacologia , Antibacterianos/farmacologia , Humanos , Infecção Hospitalar/microbiologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/tratamento farmacológico
7.
J Antimicrob Chemother ; 79(5): 1045-1050, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38507272

RESUMO

OBJECTIVES: Staphylococcus epidermidis bone and joint infections (BJIs) on material are often difficult to treat. The activity of delafloxacin has not yet been studied on S. epidermidis in this context. The aim of this study was to assess its in vitro activity compared with other fluoroquinolones, against a large collection of S. epidermidis clinical strains. METHODS: We selected 538 S. epidermidis strains isolated between January 2015 and February 2023 from six French teaching hospitals. One hundred and fifty-two strains were ofloxacin susceptible and 386 were ofloxacin resistant. Identifications were performed by MS and MICs were determined using gradient concentration strips for ofloxacin, levofloxacin, moxifloxacin and delafloxacin. RESULTS: Ofloxacin-susceptible strains were susceptible to all fluoroquinolones. Resistant strains had higher MICs of all fluoroquinolones. Strains resistant to ofloxacin (89.1%) still showed susceptibility to delafloxacin when using the Staphylococcus aureus 2021 CA-SFM/EUCAST threshold of 0.25 mg/L. In contrast, only 3.9% of the ofloxacin-resistant strains remained susceptible to delafloxacin with the 0.016 mg/L S. aureus breakpoint according to CA-SFM/EUCAST guidelines in 2022. The MIC50 was 0.094 mg/L and the MIC90 was 0.38 mg/L. CONCLUSIONS: We showed low delafloxacin MICs for ofloxacin-susceptible S. epidermidis strains and a double population for ofloxacin-resistant strains. Despite the absence of breakpoints for S. epidermidis, delafloxacin may be an option for the treatment of complex BJI, including strains with MICs of ≤0.094 mg/L, leading to 64% susceptibility. This study underlines the importance for determining specific S. epidermidis delafloxacin breakpoints for the management of BJI on material.


Assuntos
Antibacterianos , Fluoroquinolonas , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas , Staphylococcus epidermidis , Staphylococcus epidermidis/efeitos dos fármacos , Staphylococcus epidermidis/isolamento & purificação , Humanos , Fluoroquinolonas/farmacologia , Antibacterianos/farmacologia , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/tratamento farmacológico , Estudos Retrospectivos , Ofloxacino/farmacologia , Levofloxacino/farmacologia , Farmacorresistência Bacteriana , Moxifloxacina/farmacologia , França
8.
Childs Nerv Syst ; 40(6): 1765-1769, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38316673

RESUMO

PURPOSE: Staphylococcus epidermidis is the most common causative microorganism of ventriculoperitoneal shunt infections. This study aimed to compare linezolid and vancomycin treatments and to examine the effect of these antibiotics alone and combined with hyperbaric oxygen therapy on the amount of bacterial colonies in the experimental S. epidermidis shunt infection model. METHODS: A shunt catheter was placed in the cisterna magna of 49 adult male Wistar albino rats. The rats were randomly divided into seven groups, as follows: sterile control, infected control, vancomycin, linezolid, hyperbaric oxygen, vancomycin + hyperbaric oxygen, linezolid + hyperbaric oxygen. In all groups except the sterile control group, 0.2 ml 107 CFU/mL S. epidermidis was inoculated to the cisterna magna. Parenteral vancomycin was administered 40 mg/kg/day to the vancomycin groups, and 50 mg/kg/day of enteral linezolid to the linezolid groups. Hyperbaric oxygen groups were given 100% oxygen at a pressure of 2.4 ATA for 50 min a day. One day after the last treatment, colony quantities in the shunt catheters and CSF were analyzed. RESULTS: The number of CSF colonies in the linezolid group was significantly lower than in the vancomycin group (p < 0.05). The number of CSF colonies in the linezolid + HBO group was significantly lower than in the vancomycin + HBO group (p < 0.05). CONCLUSIONS: Linezolid treatment was found to be more effective than vancomycin in ventriculoperitoneal shunt infection caused by S. epidermidis. There was no statistical difference among other treatment groups. Hyperbaric oxygen therapy is shown to contribute to the sterilization of cultures.


Assuntos
Antibacterianos , Modelos Animais de Doenças , Oxigenoterapia Hiperbárica , Linezolida , Ratos Wistar , Infecções Estafilocócicas , Staphylococcus epidermidis , Vancomicina , Derivação Ventriculoperitoneal , Animais , Linezolida/uso terapêutico , Ratos , Masculino , Derivação Ventriculoperitoneal/efeitos adversos , Oxigenoterapia Hiperbárica/métodos , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus epidermidis/efeitos dos fármacos , Antibacterianos/uso terapêutico , Acetamidas/uso terapêutico , Oxazolidinonas/uso terapêutico
9.
Sci Rep ; 12(1): 13827, 2022 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-35970866

RESUMO

A new series of N-thioacylated ciprofloxacin 3a-n were designed and synthesized based on Willgerodt-Kindler reaction. The results of in vitro urease inhibitory assay indicated that almost all the synthesized compounds 3a-n (IC50 = 2.05 ± 0.03-32.49 ± 0.32 µM) were more potent than standard inhibitors, hydroxyurea (IC50 = 100 ± 2.5 µM) and thiourea (IC50 = 23 ± 0.84 µM). The study of antibacterial activity against Gram-positive species (S. aureus and S. epidermidis) revealed that the majority of compounds were more active than ciprofloxacin as the standard drug, and 3h derivative bearing 3-fluoro group had the same effect as ciprofloxacin against Gram-negative bacteria (P. aeruginosa and E. coli). Based on molecular dynamic simulations, compound 3n exhibited pronounced interactions with the critical residues of the urease active site and mobile flap pocket so that the quinolone ring coordinated toward the metal bi-nickel center and the essential residues at the flap site like His593, His594, and Arg609. These interactions caused blocking the active site and stabilized the movement of the mobile flap at the entrance of the active site channel, which significantly reduced the catalytic activity of urease. Noteworthy, 3n also exhibited IC50 values of 5.59 ± 2.38 and 5.72 ± 1.312 µg/ml to inhibit urease enzyme against C. neoformans and P. vulgaris in the ureolytic assay.


Assuntos
Antibacterianos , Ciprofloxacina , Inibidores Enzimáticos , Urease , Antibacterianos/química , Ciprofloxacina/farmacologia , Inibidores Enzimáticos/química , Escherichia coli/efeitos dos fármacos , Simulação de Acoplamento Molecular , Estrutura Molecular , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus epidermidis/efeitos dos fármacos , Relação Estrutura-Atividade , Urease/antagonistas & inibidores
10.
Eur J Med Chem ; 241: 114647, 2022 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-35963132

RESUMO

In this study, indlomycin, an inhibitor of tryptophanyl-tRNA synthetase (TrpRS), and 29 racemic indolmycin derivatives were synthesized, their antibacterial activity were evaluated against methicillin-resistant Staphylococcus aureus (S. aureus) NRS384, ATCC29213, and Escherichia coli (E. coli) ATCC25922 strains. Compounds (±)-7a, (±)-7b, (±)-7c and (±)-7e exhibited minimum inhibitory concentration (MIC) values of 1-2 µg/mL against S. aureus NRS384 and ATCC29213, exhibiting significant antibacterial activity, but none of the compounds exhibited antibacterial activity against E. coli. To investigate the effect of conformation on antibacterial activity, seven racemic compounds with good antibacterial activity were separated, and the antibacterial activity of these 14 compounds was evaluated on 25 bacterial strains. This revealed that the isomers with natural conformations (1'R, 5S) had significantly better antibacterial activity than the enantiomeric isomers and racemates. Compounds 7aa, 7ba, 7ca, and 7ea exhibited good antibacterial activity against 21 strains of S. aureus and S. epidermidis with MIC values of 0.125-2 µg/mL, which were superior to that of vancomycin, used in clinical practice. The compounds 7aa, 7ba, 7ca and 7ea were moderately bound to plasma proteins and were stable in the whole blood of CD-1 mice. In conclusion, a series of new indomycin derivatives with stronger antibacterial activity against G+ bacteria were obtained.


Assuntos
Antibacterianos , Indóis , Triptofano-tRNA Ligase , Animais , Antibacterianos/farmacologia , Proteínas de Bactérias , Escherichia coli/efeitos dos fármacos , Indóis/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Camundongos , Testes de Sensibilidade Microbiana , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus epidermidis/efeitos dos fármacos , Triptofano-tRNA Ligase/antagonistas & inibidores
11.
Proc Natl Acad Sci U S A ; 119(26): e2200348119, 2022 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-35727974

RESUMO

Immune checkpoint inhibitors (ICIs) are essential components of the cancer therapeutic armamentarium. While ICIs have demonstrated remarkable clinical responses, they can be accompanied by immune-related adverse events (irAEs). These inflammatory side effects are of unclear etiology and impact virtually all organ systems, with the most common being sites colonized by the microbiota such as the skin and gastrointestinal tract. Here, we establish a mouse model of commensal bacteria-driven skin irAEs and demonstrate that immune checkpoint inhibition unleashes commensal-specific inflammatory T cell responses. These aberrant responses were dependent on production of IL-17 by commensal-specific T cells and induced pathology that recapitulated the cutaneous inflammation seen in patients treated with ICIs. Importantly, aberrant T cell responses unleashed by ICIs were sufficient to perpetuate inflammatory memory responses to the microbiota months following the cessation of treatment. Altogether, we have established a mouse model of skin irAEs and reveal that ICIs unleash aberrant immune responses against skin commensals, with long-lasting inflammatory consequences.


Assuntos
Dermatite , Inibidores de Checkpoint Imunológico , Microbiota , Animais , Dermatite/imunologia , Dermatite/microbiologia , Modelos Animais de Doenças , Inibidores de Checkpoint Imunológico/efeitos adversos , Imunidade/efeitos dos fármacos , Interleucina-17/metabolismo , Camundongos , Microbiota/efeitos dos fármacos , Microbiota/imunologia , Staphylococcus epidermidis/efeitos dos fármacos , Staphylococcus epidermidis/imunologia , Simbiose/efeitos dos fármacos , Linfócitos T/imunologia
12.
Biomed Pharmacother ; 147: 112670, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35123230

RESUMO

Methicillin-resistant Staphylococcus epidermidis (MRSE) bacteria are being recognized as true pathogens as they are able to resist methicillin and commonly form biofilms. Recent studies have shown that antimicrobial peptides (AMPs) are promising agents against biofilm-associated bacterial infections. In this study, we aimed to explore the antibiofilm activity of melittin, either alone or in combination with vancomycin and rifampin, against biofilm-producing MRSE strains. Minimum biofilm preventive concentration (MBPC), minimum biofilm inhibition concentration (MBIC), and minimum biofilm eradication concentration (MBEC), as well as fractional biofilm preventive-, inhibitory-, and eradication concentrations (FBPCi, FBICi, and FBECi), were determined for the antimicrobial agents tested. Cytotoxicity and hemolytic activity of melittin at its synergistic concentration were examined on human embryonic kidney cells (HEK-293) and Red Blood Cells (RBCs), respectively. The effect of melittin on the downregulation of biofilm-associated genes was explored using Real-Time PCR. MBPC, MBIC, and MBEC values for melittin were in the range of 0.625-20, 0.625-20, and 10-40 µg/µL, respectively. Melittin showed high synergy (FBPCi, FBICi and FBECi < 0.5). The synergism resulted in a 64-512-fold, 2-16 and 2-8-fold reduction in melittin, rifampicin and vancomycin concentrations, respectively. The synergistic melittin concentration found to be effective did not manifest either cytotoxicity on HEK-293 or hemolytic activity on RBCs. Results showed that melittin downregulated the expression of biofilm-associated icaA, aap, and psm genes in all isolates tested, ranging from 0.04-folds to 2.11-folds for icaA and from 0.05 to 3.76-folds for aap and psm. The preventive and therapeutic indexes of melittin were improved 8-fold when combined with vancomycin and rifampin. Based on these findings, the combination of melittin with conventional antibiotics could be proposed for treating or preventing biofilm-associated MRSE infections.


Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Meliteno/farmacologia , Resistência a Meticilina , Staphylococcus epidermidis/efeitos dos fármacos , Antibacterianos/administração & dosagem , Relação Dose-Resposta a Droga , Regulação para Baixo , Farmacorresistência Bacteriana Múltipla , Sinergismo Farmacológico , Quimioterapia Combinada , Genes Bacterianos , Células HEK293 , Humanos , Meliteno/administração & dosagem , Testes de Sensibilidade Microbiana , Rifampina/administração & dosagem , Rifampina/farmacologia , Vancomicina/administração & dosagem , Vancomicina/farmacologia
13.
Molecules ; 27(2)2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35056783

RESUMO

To meet the demand for alternatives to commonly used antibiotics, this paper evaluates the antimicrobial potential of arene-ruthenium(II) complexes and their salts, which may be of value in antibacterial treatment. Their antimicrobial activity (MIC, MBC/MFC) was examined in vitro against Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Pseudomonas aeruginosa, Proteus vulgaris and Candida albicans and compared with classic antibiotics used as therapeutics. Selected arene-ruthenium(II) complexes were found to have synergistic effects with oxacillin and vancomycin against staphylococci. Their bactericidal effect was found to be associated with cell lysis and the ability to cut microbial DNA. To confirm the safety of the tested arene-ruthenium(II) complexes in vivo, their cytotoxicity was also investigated against normal human foreskin fibroblasts (HFF-1). In addition, the antioxidant and thus pro-health potential of the compounds, i.e., their nonenzymatic antioxidant capacity (NEAC), was determined by two different methods: ferric-TPTZ complex and DPPH assay.


Assuntos
Antibacterianos/farmacologia , Resistência Microbiana a Medicamentos/efeitos dos fármacos , Hidrocarbonetos Aromáticos/farmacologia , Pirazóis/farmacologia , Compostos de Rutênio/farmacologia , Antibacterianos/química , Antioxidantes/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Sinergismo Farmacológico , Fibroblastos/efeitos dos fármacos , Prepúcio do Pênis/citologia , Prepúcio do Pênis/efeitos dos fármacos , Sequestradores de Radicais Livres/farmacologia , Humanos , Hidrocarbonetos Aromáticos/química , Masculino , Oxacilina/farmacologia , Pirazóis/química , Compostos de Rutênio/química , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus epidermidis/efeitos dos fármacos , Vancomicina/farmacologia
14.
Molecules ; 27(2)2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-35056798

RESUMO

Zizyphus lotus L. is a perennial shrub particularly used in Algerian folk medicine, but little is known concerning the lipophilic compounds in the most frequently used parts, namely, root bark, pulp, leaves and seeds, which are associated with health benefits. In this vein, the lipophilic fractions of these morphological parts of Z. lotus from Morocco were studied by gas chromatography-mass spectrometry (GC-MS), and their antiproliferative and antimicrobial activities were evaluated. GC-MS analysis allowed the identification and quantification of 99 lipophilic compounds, including fatty acids, long-chain aliphatic alcohols, pentacyclic triterpenic compounds, sterols, monoglycerides, aromatic compounds and other minor components. Lipophilic extracts of pulp, leaves and seeds were revealed to be mainly composed of fatty acids, representing 54.3-88.6% of the total compounds detected. The leaves and seeds were particularly rich in unsaturated fatty acids, namely, (9Z,12Z)-octadeca-9,12-dienoic acid (2431 mg kg-1 of dry weight) and (9Z)-octadec-9-enoic acid (6255 mg kg-1 of dry weight). In contrast, root bark contained a high content of pentacyclic triterpenic compounds, particularly betulinic acid, accounting for 9838 mg kg-1 of dry weight. Root bark extract showed promising antiproliferative activity against a triple-negative breast cancer cell line, MDA-MB-231, with a half-maximal inhibitory concentration (IC50) = 4.23 ± 0.18 µg mL-1 of extract. Leaf extract displayed interesting antimicrobial activity against Escherichia coli, methicillin-sensitive Staphylococcus aureus and Staphylococcus epidermis, presenting minimum inhibitory concentration (MIC) values from 1024 to 2048 µg mL-1 of extract. Our results demonstrate that Zizyphus lotus L. is a source of promising bioactive components, which can be exploited as natural ingredients in pharmaceutical formulations.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Ziziphus/química , Álcoois/análise , Antibacterianos/análise , Antineoplásicos Fitogênicos/análise , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Ácidos Graxos/análise , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Testes de Sensibilidade Microbiana , Monoglicerídeos/análise , Marrocos , Extratos Vegetais/análise , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus epidermidis/efeitos dos fármacos , Esteróis/análise , Triterpenos/análise
15.
Molecules ; 27(2)2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-35056804

RESUMO

Fungal laccase obtained from a Cerrena unicolor strain was used as an effective biocatalyst for the transformation of 8-anilino-1-naphthalenesulfonic acid into a green-coloured antibacterial compound, which can be considered as both an antimicrobial agent and a textile dye, simultaneously. The process of biosynthesis was performed in buffered solutions containing methanol as a co-solvent, allowing better solubilisation of substrate. The transformation process was optimised in terms of the buffer pH value, laccase activity, and concentrations of the substrate and co-solvent. The crude product obtained exhibited low cytotoxicity, antibacterial properties against Staphylococcus aureus and Staphylococcus epidermidis, and antioxidant properties. Moreover, the synthesised green-coloured compound proved non-allergenic and demonstrated a high efficiency of dyeing wool fibres.


Assuntos
Naftalenossulfonato de Anilina/metabolismo , Antibacterianos/química , Antibacterianos/farmacologia , Corantes/química , Corantes/farmacologia , Lacase/metabolismo , Adulto , Idoso , Aliivibrio fischeri/efeitos dos fármacos , Naftalenossulfonato de Anilina/química , Antibacterianos/biossíntese , Antibacterianos/toxicidade , Antioxidantes/química , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Antioxidantes/toxicidade , Biocatálise , Linhagem Celular , Colo/efeitos dos fármacos , Corantes/metabolismo , Corantes/toxicidade , Células Epiteliais/efeitos dos fármacos , Feminino , Fibroblastos/efeitos dos fármacos , Fungos/enzimologia , Voluntários Saudáveis , Humanos , Hipersensibilidade , Lacase/química , Masculino , Pessoa de Meia-Idade , Oxirredução , Pele/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus epidermidis/efeitos dos fármacos
16.
Sci Rep ; 12(1): 676, 2022 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-35027620

RESUMO

Silver nanoparticles (AgNPs) gained significant attention due to their activity against microbial pathogens, cancer cells, and viral particles etc. Traditional fabrication methods require hazardous chemicals as reducing agents and their usage and disposal pose a significant hazard to environmental ecosystem. Here, a de novo, robust, cost effective and an eco-friendly method is reported to fabricate AgNPs irradiated with sunlight (SL) while using Salvadora persica root extract (SPE) as reducing agent. Sunlight (SL) irradiated S. persica silver nanoparticles (SpNPs) i.e., SL-SpNPs were characterized using multiple techniques and their antibacterial efficacy was evaluated. The SL-SpNPs were synthesized in 10 min. Field emission scanning electron microscopy (FE-SEM) and transmission electron microscopy (TEM) analysis revealed their spherical morphology with a size range of 4.5-39.7 nm, while surface plasmon resonance (SPR) peaked at 425 nm. Fourier transform infrared spectroscopy (FTIR) analysis suggested that the reduction of SL-SpNPs was due to the presence of phytochemicals in the SPE. Furthermore, X-ray powder diffraction (P-XRD) pattern depicted the crystal structure of SL-SpNPs, hence proving the presence of AgNPs. Further the antibacterial studies were carried out against Escherichia coli (ATCC 11229) and Staphylococcus epidermidis (ATCC 12228) using Kirby Bauer method. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) for E. coli were determined to be 1.5 µg/mL and 3.0 µg/mL respectively while MIC and MBC values for S. epidermidis were found to be 12.5 µg/mL and 25 µg/mL respectively. The solar irradiation-based fabrication method and resulting SL-SpNPs can find their utility in many biomedical and environmental applications.


Assuntos
Escherichia coli/efeitos dos fármacos , Química Verde/métodos , Nanopartículas Metálicas , Prata/química , Prata/farmacologia , Staphylococcus epidermidis/efeitos dos fármacos , Luz Solar , Farmacorresistência Bacteriana , Ecossistema , Testes de Sensibilidade Microbiana , Tamanho da Partícula
18.
Proc Natl Acad Sci U S A ; 119(3)2022 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-35012978

RESUMO

Preventing pathogenic viral and bacterial transmission in the human environment is critical, especially in potential outbreaks that may be caused by the release of ancient bacteria currently trapped in the permafrost. Existing commercial disinfectants present issues such as a high carbon footprint. This study proposes a sustainable alternative, a bioliquid derived from biomass prepared by hydrothermal liquefaction. Results indicate a high inactivation rate of pathogenic virus and bacteria by the as-prepared bioliquid, such as up to 99.99% for H1N1, H5N1, H7N9 influenza A virus, and Bacillus subtilis var. niger spores and 99.49% for Bacillus anthracis Inactivation of Escherichia coli and Staphylococcus epidermidis confirmed that low-molecular-weight and low-polarity compounds in bioliquid are potential antibacterial components. High temperatures promoted the production of antibacterial substances via depolymerization and dehydration reactions. Moreover, bioliquid was innoxious as confirmed by the rabbit skin test, and the cost per kilogram of the bioliquid was $0.04427, which is notably lower than that of commercial disinfectants. This study demonstrates the potential of biomass to support our biosafety with greater environmental sustainability.


Assuntos
Biomassa , Contenção de Riscos Biológicos , Meio Ambiente , Energia Renovável , Antibacterianos/farmacologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/ultraestrutura , Humanos , Testes de Sensibilidade Microbiana , Peso Molecular , Pandemias , Staphylococcus epidermidis/efeitos dos fármacos , Staphylococcus epidermidis/ultraestrutura
19.
Chem Biodivers ; 19(1): e202100616, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34812587

RESUMO

Serious bacterial infections could be caused by Gram-positive microorganisms, in particular methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis. Aiming to address this challenging issue by developing the potent and selective antimicrobial lead structures against methicillin-resistant Staphylococcus spp., herein, we report in vitro evaluation of quinolinequinones (QQ1-QQ10) against the Gram-negative and Gram-positive strains using the broth microdilution technique. The design principle of the quinolinequinones was based on the variation of the structures attached to the 1,4-quinone moiety and substituent(s) within amino phenyl moiety. A series of ten quinolinequinones displayed activity mainly against the Gram-positive strains with a minimal inhibitory concentration (MIC=1.22-1250 mg/L) within the Clinical and Laboratory Standards Institute (CLSI) levels. Interestingly, QQ3, QQ5, and QQ6 displayed equal antibacterial inhibitory activity against S. aureus (MIC=1.22 mg/L), respectively, to the standard positive control Cefuroxime-Na. QQ2, QQ3, and QQ5 had the best inhibitory activity with the MIC value of 1.22 mg/L (4-fold more potent compared reference standard Cefuroxime) against S. epidermidis. On the other hand, QQ3 was the most effective quinolinequinone against fungi, in particular C. albicans. The identified lead quinolinequinones (QQ3 and QQ5) with a comprehensive analysis of structure-activity relationships and further studies showed high activity against methicillin-resistant Staphylococcus spp. It is worth noting that the isopropyl group has importance for excellent bioactivity. Remarkably, the in vitro antibiofilm and bactericidal activities (each of 32 clinically obtained strains of Gram-positive bacteria) of the selected two quinolinequinones (QQ3 and QQ5) have been evaluated for the mode of action in addition to the time-kill curve study.


Assuntos
Anti-Infecciosos/química , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Quinolinas/farmacologia , Anti-Infecciosos/farmacologia , Biofilmes/efeitos dos fármacos , Fungos/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Quinolinas/química , Staphylococcus epidermidis/efeitos dos fármacos , Staphylococcus epidermidis/fisiologia , Relação Estrutura-Atividade
20.
Bioorg Med Chem Lett ; 58: 128521, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-34968675

RESUMO

The synthesis and biological evaluation of eleven derivatives of the natural polyether ionophore monensin A (MON), modified at the C-26 position, is presented. Eight urethane and three ester derivatives were tested for their antimicrobial activity against different strains of Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli and Pseudomonas aeruginosa. In addition, their antiparasitic activity was also evaluated with bloodstream forms of Trypanosoma brucei. The majority of the modified ionophores were active against a variety of Gram-positive bacterial strains, including methicillin-resistant S. epidermidis, and showed better antibacterial activity than the unmodified MON. The phenyl urethane derivative of MON exhibited the most promising antibacterial activity of all tested compounds, with minimal inhibitory concentration values of 0.25-0.50 µg/ml. In contrast, none of the MON derivatives displayed higher antitrypanosomal activity than the unmodified ionophore.


Assuntos
Antibacterianos/farmacologia , Monensin/farmacologia , Tripanossomicidas/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Relação Dose-Resposta a Droga , Escherichia coli/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Monensin/análogos & derivados , Monensin/química , Testes de Sensibilidade Parasitária , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus epidermidis/efeitos dos fármacos , Relação Estrutura-Atividade , Tripanossomicidas/síntese química , Tripanossomicidas/química , Trypanosoma brucei brucei/efeitos dos fármacos
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