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Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), has been the world's driving fatal bacterial contagious disease globally. It continues a public health emergency, and around one-third of the global community has been affected by latent TB infection (LTBI). This is mostly due to the difficulty in diagnosing and treating patients with TB and LTBI. Exosomes are nanovesicles (40-100 nm) released from different cell types, containing proteins, lipids, mRNA, and miRNA, and they allow the transfer of one's cargo to other cells. The functional and diagnostic potential of exosomal miRNAs has been demonstrated in bacterial infections, including TB. Besides, it has been recognized that cells infected by intracellular pathogens such as Mtb can be secreting an exosome, which is implicated in the infection's fate. Exosomes, therefore, open a unique viewpoint on the investigative process of TB pathogenicity. This study explores the possible function of exosomal miRNAs as a diagnostic biomarker. Moreover, we include the latest data on the pathogenic and therapeutic role of exosomal miRNAs in TB.
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Exossomos/genética , RNA Mensageiro , Tuberculose/genética , Animais , Biomarcadores , Humanos , Mycobacterium tuberculosis/genética , Tuberculose/diagnóstico , Tuberculose/imunologiaRESUMO
In recent years, extreme attention has been focused on the role of immunometabolism in the regulation of immune cell responses in healthy individuals during infection, autoimmunity, and cancer. In the infection biology area, it has been shown that there is a close relationship between the immune system and the host metabolic changes. Brucella species is an intracellular coccobacillus that infects humans and mammals, which led to brucellosis. Brucella species with host-specific evolutionary mechanisms allow it to hide from or manipulate cellular immunity and achieve intracellular persistence. Intracellular bacterial pathogens such as Brucella species also employ host cell resources to replicate and persist inside the host. Targeting these host systems is one promising strategy for developing novel antimicrobials to tackle intracellular infections. This study will summarize the role of metabolic reprogramming in immune cells and their relationship to brucellosis.
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Brucella , Brucelose , Animais , Evolução Biológica , HumanosRESUMO
COVID-19 is an acute respiratory infection accompanied by pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has affected millions of people globally. To date, there are no highly efficient therapies for this infection. Probiotic bacteria can interact with the gut microbiome to strengthen the immune system, enhance immune responses, and induce appropriate immune signaling pathways. Several probiotics have been confirmed to reduce the duration of bacterial or viral infections. Immune fitness may be one of the approaches by which protection against viral infections can be reinforced. In general, prevention is more efficient than therapy in fighting viral infections. Thus, probiotics have emerged as suitable candidates for controlling these infections. During the COVID-19 pandemic, any approach with the capacity to induce mucosal and systemic reactions could potentially be useful. Here, we summarize findings regarding the effectiveness of various probiotics for preventing virus-induced respiratory infectious diseases, especially those that could be employed for COVID-19 patients. However, the benefits of probiotics are strain-specific, and it is necessary to identify the bacterial strains that are scientifically established to be beneficial.
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Tratamento Farmacológico da COVID-19 , COVID-19/prevenção & controle , Probióticos/uso terapêutico , Antivirais/farmacologia , Antivirais/uso terapêutico , COVID-19/imunologia , Vacinas contra COVID-19/farmacologia , Vacinas contra COVID-19/uso terapêutico , Disbiose , Humanos , Imunomodulação , Microbiota , Probióticos/classificação , Probióticos/farmacologia , SARS-CoV-2/patogenicidade , Especificidade da EspécieRESUMO
BACKGROUND: This study aimed to investigate the association between biocides' reduced susceptibility and the presence of efflux pump genes including cepA, qacEΔ1 and qacE in multidrug-resistant (MDR) Pseudomonas aeruginosa. METHODS AND RESULTS: The MDR P. aeruginosa isolates were collected and identified from different clinical samples. The minimum inhibitory concentrations (MIC) of four biocides (chlorhexidine gluconate 1%, benzalkonium chloride 1%, Kohrsolin® extra, and SEPTI-Turbo) were determined by microbroth dilution with and without carbonyl cyanide m-chlorophenyl hydrazone (CCCP). Polymerase chain reaction (PCR) was performed for detecting the efflux pump genes. In total, 92 MDR P. aeruginosa isolates were collected. The reduced susceptibility (8-128 µg/ml) was seen against chlorhexidine gluconate 1%, benzalkonium chloride 1%, Kohrsolin® extra, and SEPTI-Turbo in 63 (68.5%), 59 (64.1%), 64 (69.6%), and 65 (70.6%) isolates, respectively. The Kohrsolin® extra was the most effective biocide. The cepA, qacE, and qacEΔ1 were detected in 56 (60.9%), 1 (1.1%), and 34 (36.9%) isolates, respectively. There was a significant association between the presence of biocide resistance genes and reduced susceptibility to studied biocides (P = 0.00001). The CCCP had no effect on benzalkonium chloride 1% and Kohrsolin® extra, but reduced the MICs of chlorhexidine gluconate 1% and SEPTI- Turbo by 2 to 128 fold. CONCLUSIONS: The P. aeruginosa isolates exhibited varying degrees of tolerance to biocides. The cepA was the most prevalent gene. There was a significant connection between the occurrence of the efflux pump genes cepA and qacEΔ1 with reduced biocide susceptibility.
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Farmacorresistência Bacteriana/genética , Pseudomonas aeruginosa/genética , Antibacterianos/farmacologia , Compostos de Benzalcônio/farmacologia , Clorexidina/análogos & derivados , Clorexidina/farmacologia , Desinfetantes/farmacologia , Resistência a Múltiplos Medicamentos/genética , Farmacorresistência Bacteriana Múltipla/genética , Genes Bacterianos/genética , Humanos , Irã (Geográfico)/epidemiologia , Testes de Sensibilidade Microbiana/métodos , PrevalênciaRESUMO
Biofilms are microbial communities established in the self-produced extracellular substances that include up to 80% of associated microbial infections. During biofilm formation, bacterial cells shift from the planktonic forms to aggregated forms surrounded by an extracellular polymeric substance. The bacterial biofilm shows resistance against immune reactions as well as antibiotics and is potentially able to cause disorders by both device-related and nondevice-related infections. The nondevice-related bacterial biofilm infections include dental plaque, urinary tract infections, cystic fibrosis, otitis media, infective endocarditis, tonsillitis, periodontitis, necrotizing fasciitis, osteomyelitis, infectious kidney stones, and chronic inflammatory diseases. In this review, we will summarize and examine the literature about bacterial biofilm infections unrelated to indwelling devices.
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Infecções Bacterianas/microbiologia , Biofilmes/crescimento & desenvolvimento , Animais , Cateteres de Demora , HumanosRESUMO
Staphylococcus aureus is known as a common pathogen that colonizes 30% of healthy humans. Additionally, this bacterium can cause a number of serious infections, that is, endocarditis, bacteremia, pneumonia, wound, skin infections, and tissue abscesses. A variety of cellular and molecular pathways and targets are involved in response against S. aureus. Among them, microRNAs (miRNAs) have crucial roles in response against S. aureus. In this regard, it has been shown that these molecules exert their regulatory roles via modulating a wide range of events, such as inflammatory reactions, host innate, and adaptive immunity. Current works have provided insight into the crucial involvement of miRNAs in immune defense toward Staphylococcal infections. Herein, we highlighted the current findings on the deregulation of different miRNAs in S. aureus-infected cells. Moreover, we summarized the mechanisms and targets of miRNAs in S. aureus infections.
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Biomarcadores/análise , Imunidade Inata/imunologia , MicroRNAs/genética , Infecções Estafilocócicas/diagnóstico , Staphylococcus aureus/imunologia , Animais , Humanos , Imunidade Inata/genética , Infecções Estafilocócicas/genética , Infecções Estafilocócicas/imunologia , Infecções Estafilocócicas/microbiologiaRESUMO
The pandemic coronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has affected millions of people worldwide. To date, there are no proven effective therapies for this virus. Efforts made to develop antiviral strategies for the treatment of COVID-19 are underway. Respiratory viral infections, such as influenza, predispose patients to co-infections and these lead to increased disease severity and mortality. Numerous types of antibiotics such as azithromycin have been employed for the prevention and treatment of bacterial co-infection and secondary bacterial infections in patients with a viral respiratory infection (e.g., SARS-CoV-2). Although antibiotics do not directly affect SARS-CoV-2, viral respiratory infections often result in bacterial pneumonia. It is possible that some patients die from bacterial co-infection rather than virus itself. To date, a considerable number of bacterial strains have been resistant to various antibiotics such as azithromycin, and the overuse could render those or other antibiotics even less effective. Therefore, bacterial co-infection and secondary bacterial infection are considered critical risk factors for the severity and mortality rates of COVID-19. Also, the antibiotic-resistant as a result of overusing must be considered. In this review, we will summarize the bacterial co-infection and secondary bacterial infection in some featured respiratory viral infections, especially COVID-19.
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Antibacterianos/uso terapêutico , Antivirais/uso terapêutico , Infecções Bacterianas/epidemiologia , COVID-19/epidemiologia , Pandemias , Pneumonia Bacteriana/epidemiologia , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/patogenicidade , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Infecções Bacterianas/virologia , COVID-19/microbiologia , COVID-19/virologia , Coinfecção , Haemophilus influenzae/efeitos dos fármacos , Haemophilus influenzae/patogenicidade , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunidade Inata/efeitos dos fármacos , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/patogenicidade , Legionella pneumophila/efeitos dos fármacos , Legionella pneumophila/patogenicidade , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Bacteriana/microbiologia , Pneumonia Bacteriana/virologia , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/patogenicidade , Sistema Respiratório/efeitos dos fármacos , Sistema Respiratório/microbiologia , Sistema Respiratório/patologia , Sistema Respiratório/virologia , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/patogenicidade , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pneumoniae/patogenicidade , Streptococcus pyogenes/efeitos dos fármacos , Streptococcus pyogenes/patogenicidade , Tratamento Farmacológico da COVID-19RESUMO
Various bacterial species, previously known as extracellular pathogens, can reside inside different host cells by adapting to intracellular modes by forming microbial aggregates with similar characteristics to bacterial biofilms. Additionally, bacterial invasion of human cells leads to failure in antibiotic therapy, as most conventional anti-bacterial agents cannot reach intracellular biofilm in normal concentrations. Various studies have shown that bacteria such as uropathogenic Escherichia coli, Pseudomonas aeruginosa, Borrelia burgdorferi,Moraxella catarrhalis, non-typeable Haemophilus influenzae, Streptococcus pneumonia, and group A Streptococci produce biofilm-like structures within the host cells. For the first time in this review, we will describe and discuss the new information about intracellular bacterial biofilm formation and its importance in bacterial infectious diseases.
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Biofilmes , Doenças Transmissíveis , Infecções por Haemophilus , Antibacterianos/uso terapêutico , Haemophilus influenzae , Humanos , Moraxella catarrhalisRESUMO
Human colorectal cancer is the third most common cancer around the world. Colorectal cancer has various risk factors, but current works have bolded a significant activity for the microbiota of the human colon in the development of this disease. Bacterial biofilm has been mediated to non-malignant pathologies like inflammatory bowel disease but has not been fully documented in the setting of colorectal cancer. The investigation has currently found that bacterial biofilm is mediated to colon cancer in the human and linked to the location of human cancer, with almost all right-sided adenomas of colon cancers possessing bacterial biofilm, whilst left-sided cancer is rarely biofilm positive. The profound comprehension of the changes in colorectal cancer can provide interesting novel concepts for anticancer treatments. In this review, we will summarize and examine the new knowledge about the links between colorectal cancer and bacterial biofilm.
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Brucellosis poses a significant challenge in the medical field as a systemic infection with a propensity for relapse. This study presented a novel approach to brucellosis treatment, enhancing the efficacy of doxycycline and rifampicin through the use of poly (lactic-co-glycolic) acid coupled with cadmium-telluride quantum dots (Dox-Rif-PLGA@CdTe). The double emulsion solvent evaporation method was employed to prepare Dox-Rif-PLGA@CdTe. The study scrutinized the physicochemical attributes of these nanoparticles. The impact of antibiotic-loaded nanoparticles on Brucella melitensis was evaluated through well diffusion, minimum inhibitory concentration (MIC), and cell culture. The chemical analysis results demonstrated a possibility of chemical reactions occurring among the constituents of nanoparticles. Assessments using the well diffusion and MIC methods indicated that the impact of free drugs and nanoparticles on bacteria was equivalent. However, the drug-loaded nanoparticles significantly decreased the colony-forming units (CFUs) within the cell lines compared to free drugs. In conclusion, the synthesis of nanoparticles adhered to environmentally friendly practices and demonstrated safety. The sustained drug release over 100 h facilitated drug accumulation at the bacterial site, resulting in a heightened therapeutic effect on B. melitensis and improved outcomes in brucellosis treatment. The application of these synthesized nanodrugs exhibited promising therapeutic potential.
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BACKGROUND: Uropathogenic Escherichia coli (UPEC) is a common cause of urinary tract infections (UTI) in children and currently is one of the leading medical problems. Due to the increase in antibiotic resistance rate, herbal medicines with lower side effects were considered. OBJECTIVE: This study aimed to identify the afa, fimH, and sfa genes of UPEC bacteria isolated from pediatric UTI to investigate the effect of the thyme on the expression of fimH gene. STUDY DESIGN: In this cross-sectional study, 160 UPEC were isolated from pediatric UTIs. An antibiotic susceptibility test was performed on six families of antibiotics, including beta-lactams, quinolones, aminoglycosides, carbapenems, sulfonamides, and nitrofurantoin. The micro-broth dilution method was used to determine MIC of thymol. The biofilm production ability of isolated strains was quantified by the microtiter plate method. The PCR technique was used to detectfimH, afa, and sfa adhesion genes, and real-time PCR was used to measure the fimHgene expression. RESULTS: The results of the antibiogram showed that the lowest and highest resistance related to meropenem and imipenem (zero), and 72.5% for cephalothin. MIC showed 80.7% of the isolates were sensitive to thymol. The biofilm production results showed that 3.12%, 53.75%, and 43.12% of the isolates were strong, weak, and no-biofilm (Zero) producers, respectively. After thymol treatment, 26.25% and 73.75% of isolates were weak and no-producer (Zero) biofilms, respectively and there was a significant correlation (P-value = 0.042) compared to the control group. The frequency of fimH, sfa, and afa genes was 53.1%, 49.4%, and 29.4%, respectively. The expression of fimHgene after 48 h thymol treatment decreased significantly (P-value< 0.05). CONCLUSION: Due to the significant effects of thymol in preventing the expression of the adhesion gene (fimH) of UPEC bacteria, our study is a proof-of-concept study evaluating bacterial sensitivity to Thymol and its effect on biofilm production in vitro. Given the demonstrated promising results of Thymol's effectiveness and the increase in bacterial antibiotic resistance, further studies should be undertaken to determine the safety and effectiveness of Thymol use in the clinical treatment of urinary tract infection. We believe that Thymol may prove to be an effective adjunct to the treatment of bacterial urinary tract infections.
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Infecções por Escherichia coli , Infecções Urinárias , Escherichia coli Uropatogênica , Humanos , Criança , Timol/farmacologia , Timol/uso terapêutico , Escherichia coli Uropatogênica/genética , Estudos Transversais , Infecções por Escherichia coli/tratamento farmacológico , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/microbiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêuticoRESUMO
Background: During the Coronavirus Pandemic, the use of masks has increased significantly. The lack of control on hygiene protocols and the need to use PPE properly increases the spread of bacterial infection. The purpose of this study was to investigate the degree of contamination and frequency of bacterial species isolated from surgical and N95 masks used by hospital personnel. Methods: A total number of 175 masks were collected from staff working in Sina hospital (Hamadan province, Iran) during the first six months of 2022. The bacterial contamination of masks were evaluated and identified using biochemical kits. Antimicrobial susceptibility testing of the isolates were done using Kirby-Bauer methods and MIC were assessed for each isolate against different disinfectants (Sodium hypochlorite 5%, Hydrogen Peroxide 3%, Ethanol 70% and Deconex). Results: Of 175 masks, 471 bacterial isolates were detected including 9 species. The most prevalent strain were Coagulase negative Staphylococcus (28%) followed by Acinetobacter (20.8%) and Pseudomonas (13.8%), while, Klebsiealla and Enterococcus were the least frequent species with the rate of 3.8% and 1.2%, respectively. The results of MIC methods indicated that all 471 strains were resistant to ehtanol70% and sensitive to hydrogen peroxide 3%. Furthermore, the mean average of Deconex inhibitory effect is lower than Sodium hypochlorite 5%. Conclusions: According to the results of this study, there was a high prevalence of CoNS, Acinetobacter and Pseudomonas in hospital with a high resistance pattern against antibiotics especially Ampicillin and disinfectants.
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Staphylococcus epidermis is one of the most frequent causes of device-associated infections due to biofilm formation. Current reports noted that subinhibitory concentrations of antibiotics induce biofilm production in some bacteria. Accordingly, we evaluated the effect of exposure of different subinhibitory concentrations of cloxacillin, cefazolin, clindamycin, and vancomycin on the biofilm formation of methicillin-resistant S. epidermidis (MRSE). Antimicrobial susceptibility testing and minimum inhibitory/bactericidal concentration of antimicrobial agents were determined. MRSE isolates were selected, and their biofilm formation ability was evaluated. The effect of subinhibitory concentrations of cloxacillin, cefazolin, clindamycin, and vancomycin, antibiotics selected among common choices in the clinic, on MRSE biofilm formation was determined by the microtitre method. Besides, the effect of subinhibitory concentrations of cloxacillin, cefazolin, clindamycin, and vancomycin on the expression of the biofilm-associated genes icaA and atlE was evaluated by Reverse-transcription quantitative real-time polymerase chain reaction (RT-qPCR). Antimicrobial susceptibility patterns of MRSE strains showed a high level of resistance as follows: 80%, 53.3%, 33.3%, 33.3%, and 26.6%, for erythromycin, trimethoprim-sulfamethoxazole, tetracycline, clindamycin, and gentamicin, respectively. Besides, 73.3% of S. epidermidis strains were Multidrug-resistant (MDR). Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values were in the range of 0.5 to512 µg/mL and 1 to1024 µg/mL for cloxacillin, 0.125 to256 µg/mL and 1 to512 µg/mL for cefazolin, 0.125 to64 µg/mL and 4 to>1024 µg/mL for clindamycin, and 2 to32 µg/mL and 4 to32 µg/mL for vancomycin, respectively. The findings showed that subinhibitory concentrations of cloxacillin, cefazolin, and clindamycin induce biofilm production in MRSE strains. In particular, the OD values of strains were in the range of 0.09-0.95, 0.05-0.86, and 0.06-1 toward cloxacillin, cefazolin, and clindamycin, respectively. On the other hand, exposure to subinhibitory vancomycin concentrations did not increase the biofilm formation in MRSE strains. The findings also demonstrated that sub-MIC of antibiotics up-regulated biofilm-associated genes. In particular, atlE and icaA were up-regulated 0.062 to 1.16 and 0.078 to 1.48 folds, respectively, for cloxacillin, 0.11 to 0.8, and 0.1 to 1.3 folds for cefazolin, 0.18 to 0.98, and 0.19 to 1.4 folds, respectively, for clindamycin. In contrast, the results showed that sub-MIC of vancomycin did not increase the biofilm-associated genes. These findings overall show that exposure to sub-MIC of traditional antibiotics can cause biofilm induction in MRSE, thereby increasing the survival and persistence on various surfaces that worsen the condition of comorbid infections.
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Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Humanos , Staphylococcus epidermidis , Cefazolina/farmacologia , Clindamicina/farmacologia , Vancomicina/farmacologia , Resistência a Meticilina , Cloxacilina , Infecções Estafilocócicas/microbiologia , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , BiofilmesRESUMO
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.
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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/farmacologiaRESUMO
Methicillin-resistant Staphylococcus epidermidis (MRSE) strains are increasingly emerging as serious pathogens because they can be resistant to many antibiotics called multidrug resistance (MDR) that limit the therapeutic options. In the case of vancomycin- and rifampin-resistant MDR-MRSE, the physicians are not allowed to increase the doses of antibiotics because of severe toxicity. Accordingly, we investigated the synergistic activity of melittin antimicrobial peptide with vancomycin and rifampin against vancomycin-resistant, and rifampin-resistant MDR-MRSE isolates. Minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), fractional inhibitory concentration index (FICi), and fractional bactericidal concentration index (FBCi) of antimicrobial agents against isolates were determined. Coagulate activities and serum and salt stability as well as melittin cytotoxicity on the human embryonic kidney (HEK) 293 cells and human red blood cells (RBCs) at their synergistic concentrations. MIC and MBC values for melittin were in the range of 0.312-2.5 and 0.312-5, respectively. Results also showed that the interaction of melittin with drugs was highly synergistic in which the geometric means of FICi and FBCi were < 0.5. Induced synergism led to a decrease in melittin, rifampin, and vancomycin concentrations by 8-1,020, 2-16, and 4-16-folds, respectively. This phenomenon caused a reduction in melittin toxicity by which the synergistic concentration of melittin needed to kill bacteria did not show cytotoxicity and hemolytic activity. Besides, no coagulation activity was found for the synergistic and alone concentrations of melittin in both Prothrombin Time (PT) and Partial Thromboplastin Time (PTT). Interestingly, the antibacterial activity of melittin in Mueller Hinton Broth (MHB) containing human serum did no significant differences between MIC and MBC values of melittin in MHB and MHB containing 10% human serum. The present findings showed that the therapeutic index of melittin was improved by 32.08- and 12.82-folds when combined with vancomycin and rifampin, respectively. Taken together, the obtained data show that melittin alone was effective against MDR-MRSE isolates and this antimicrobial peptide showed highly synergistic effects with vancomycin and rifampin without causing toxicity. Therefore, the combination of melittin and traditional antibiotics could be a promising strategy for the treatment of infections caused by MDR-MRSE.
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Following cancer, cells in a particular tissue can no longer respond to the factors involved in controlling cell survival, differentiation, proliferation, and death. In recent years, it has been indicated that alterations in the gut microbiota components, intestinal epithelium, and host immune system are associated with cancer incidence. Also, it has been demonstrated that the short-chain fatty acids (SCFAs) generated by gut microbiota are vitally crucial in cell homeostasis as they contribute to the modulation of histone deacetylases (HDACs), resulting effected cell attachment, immune cell immigration, cytokine production, chemotaxis, and the programmed cell death. Therefore, the manipulation of SCFA levels in the intestinal tract by alterations in the microbiota structure can be potentially taken into consideration for cancer treatment/prevention. In the current study, we will explain the most recent findings on the detrimental or protective roles of SFCA (particularly butyrate, propionate, and acetate) in several cancers, including bladder, colon, breast, stomach, liver, lung, pancreas, and prostate cancers.
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Anticarcinógenos/farmacologia , Carcinogênese/efeitos dos fármacos , Ácidos Graxos Voláteis/farmacologia , Microbiota , Animais , Microbioma Gastrointestinal , HumanosRESUMO
During the past decade, accumulating evidence from the research highlights the suggested effects of bacterial communities of the human gut microbiota and their metabolites on health and disease. In this regard, microbiota-derived metabolites and their receptors, beyond the immune system, maintain metabolism homeostasis, which is essential to maintain the host's health by balancing the utilization and intake of nutrients. It has been shown that gut bacterial dysbiosis can cause pathology and altered bacterial metabolites' formation, resulting in dysregulation of the immune system and metabolism. The short-chain fatty acids (SCFAs), such as butyrate, acetate, and succinate, are produced due to the fermentation process of bacteria in the gut. It has been noted remodeling in the gut microbiota metabolites associated with the pathophysiology of several neurological disorders, such as Alzheimer's disease, multiple sclerosis, Parkinson's disease, amyotrophic lateral sclerosis, stress, anxiety, depression, autism, vascular dementia, schizophrenia, stroke, and neuromyelitis optica spectrum disorders, among others. This review will discuss the current evidence from the most significant studies dealing with some SCFAs from gut microbial metabolism with selected neurological disorders.
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Ácidos Graxos Voláteis/metabolismo , Microbioma Gastrointestinal/fisiologia , Microbiota/fisiologia , Doenças do Sistema Nervoso/metabolismo , Doenças do Sistema Nervoso/microbiologia , Animais , HumanosRESUMO
The novel coronavirus disease 2019 (COVID-19) pandemic has imposed significant public health problems for the human populations worldwide after the 1918 influenza A virus (IVA) (H1N1) pandemic. Although numerous efforts have been made to unravel the mechanisms underlying the coronavirus, a notable gap remains in our perception of the COVID-19 pathogenesis. The innate and adaptive immune systems have a pivotal role in the fate of viral infections, such as COVID-19 pandemic. MicroRNAs (miRNAs) are known as short noncoding RNA molecules and appear as indispensable governors of almost any cellular means. Several lines of evidence demonstrate that miRNAs participate in essential mechanisms of cell biology, regulation of the immune system, and the onset and progression of numerous types of disorders. The immune responses to viral respiratory infections (VRIs), including influenza virus (IV), respiratory syncytial virus (RSV), and rhinovirus (RV), are correlated with the ectopic expression of miRNAs. Alterations of the miRNA expression in epithelial cells may contribute to the pathogenesis of chronic and acute airway infections. Hence, analyzing the role of these types of nucleotides in antiviral immune responses and the characterization of miRNA target genes might contribute to understanding the mechanisms of the interplay between the host and viruses, and in the future, potentially result in discovering therapeutic strategies for the prevention and treatment of acute COVID-19 infection. In this article, we present a general review of current studies concerning the function of miRNAs in different VRIs, particularly in coronavirus infection, and address all available therapeutic prospects to mitigate the burden of viral infections.
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COVID-19/genética , MicroRNAs , SARS-CoV-2 , Animais , Biomarcadores , COVID-19/diagnóstico , COVID-19/imunologia , COVID-19/terapia , HumanosRESUMO
Coronavirus disease 2019 (COVID-19) is a pandemic infectious disease caused by the novel coronavirus called SARS-CoV-2. There is a gap in our understanding regarding the immunopathogenesis of COVID-19. However, many clinical trials are underway across the world for screening effective drugs against COVID-19. Nevertheless, currently, no proven effective therapies for this virus exists. The vaccines are deemed as a significant part of disease prevention for emerging viral diseases, since, in several cases, other therapeutic choices are limited or non-existent, or that diseases result in such an accelerated clinical worsening that the efficacy of treatments is restricted. Therefore, effective vaccines against COVID-19 are urgently required to overcome the tremendous burden of mortality and morbidity correlated with SARS-CoV-2. In this review, we will describe the latest evidence regarding outstanding vaccine approaches and the challenges for vaccine production.