Melo, Andressa Leite Ferraz deRossato, LuanaBarbosa, Marcelo dos SantosPalozi, Rhanany Alan Calloi...
8页
查看更多>>摘要：The emergence of resistance to antibiotics has become a global challenge as far as the control and treatment of nosocomial infections are concerned. Compared to the planktonic state, biofilms generally confer more resistance to antibiotics and may become a potential source of infection. Researchers are thus focused on developing novel drugs not as vulnerable as the current ones to bacterial resistance mechanisms and also able to target bacteria in biofilms. Natural products, especially those derived from plant sources, have substantiated significant medicinal activity with unique properties, making them perfect candidates for these much-needed therapeutics. Despite being a vast resource of antimicrobial molecules, limitations, including the low concentration of the extracted active compound and bioavailability, challenge the clinical application of medicinal plants to combat these infections. Nanotechnology through green synthesis is one of the strategies to explore the medicinal potential of plants. Research has established the promising outcome of this method in antibiofilm activity, in addition to improved drug delivery, targeting, and pharmacokinetic profiles. This review summarized the current knowledge on the potentialities of plant products as antibiotic adjuvants to restore the therapeutic activity of drugs. We also discussed biotechnological advances in medicinal plants to fight and eradicate biofilm-forming microorganisms.
查看更多>>摘要：The bacterial wilt caused by Ralstonia solanacearum is a destructive plant disease globally. Since a completely non-biological control measure could be a matter of environmental concern, investigations of developing ecofriendly strategies are required to control this phytopathogen. Attenuation of the bacterial virulence in addition to destroying the pathogen may be an alternative and overarching approach to control this disease. In this study, we have explored the potentiality of a vertically transmitted endophytic fungus Penicillium sp. PM031 isolated from stem of in vitro grown, wilt susceptible tomato cultivar to control this phytopathogen. The endophytic fungus was unable to inhibit the bacterial growth during direct confrontation in co-culture system; rather its growth and extracellular secretion were affected by the bacterium. Interestingly, the PM031-derived endo-metabolites, containing ~80% of lipid molecules, showed the dose-dependent growth inhibitory effect against R. solanacearum. Metabolite treatment with a concentration of 2500 and 5000 mu g/ml significantly inhibited the bacterial growth 24.72% and 64.31%, respectively. Higher concentrations of endo-metabolite treatment exhibited antibacterial activity by rupturing cellular membranes. Furthermore, the endo-metabolites negatively influence the virulence factors necessary in early phases of bacterial infection, such as motility and biofilm formation. Our study highlights even if an endophytic fungus associated with the susceptible host plant cannot tackle R. solanacearum directly, its lipid-rich metabolites have potential to attenuate the virulence of phytopathogen. We believe this study can be a stepping stone to develop suitable formulations to control the bacterial wilt in a sustainable way, which will reduce excessive uses of synthetic bactericides.
查看更多>>摘要：Streptococcus mutans (S. mutans) is considered the main causative agent of dental caries. The study aims to evaluate the antimicrobial activity of a natural plant product, pure 4,5 ''-dihydroxy-anthraquinone-2-carboxylic acid (Rhein) against S. mutans. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was used to determine the viability of immortalized human keratinocytes (HaCaT) following treatment with Rhein. Assay for antimicrobial activity and the time-killing test were performed to evaluate Rhein effects against planktonic S. mutans. The effect of different concentrations of Rhein on biofilm biomass and the metabolism of biofilm cells were evaluated through crystal violet and MTT assays. Further, Rhein-treated biofilms were viewed by confocal laser scanning microscopy. Rhein effects on acid production and acid environment tolerance were also assessed. The minimum inhibitory concentration (MIC) of Rhein, exerting bacteriostatic action on 90% of planktonic S. mutans (MIC90), was 5.69 mu g/mL. MIC and sub-MIC concentrations of Rhein affected the metabolism of biofilm cells and disrupted biofilm biomass with minimal biofilm eradication concentrations (MBEC) inducing 50% (MBEC50) and 90% eradication (MBEC90) of 6.31 and > 50 mu g/mL, respectively. Confocal images displayed a significant reduction in biofilm biomass following treatment with increasing concentrations of the compound. Rhein also reduced the virulence of the biofilm by affecting acid production and acid tolerance. Conversely, active concentrations of Rhein did not affect HaCaT cell viability. Together, these findings indicate that Rhein, a natural product that counteracts the virulence of S. mutans, may represent a novel therapeutic option for dental caries.
查看更多>>摘要：The regulation of the activity of proteases by endogenous inhibitors is a common trend in almost all forms of life. Here, we review the endogenous inhibitors of cysteine proteases of three major pathogenic parasitic protozoa. The review focuses on members of the genus Plasmodium, Entamoeba, and Leishmania. Research in this domain has revealed the presence of only chagasin-like inhibitors of cysteine proteases that house a beta-barrel immunoglobulin-fold and inhibit the target proteases using a 3-loop inhibitory mechanism in these pathogens. Inhibitors of cysteine proteases are highly evolvable enzymes that target a broad spectrum of pathogenic cysteine proteases with a proclivity for those involved in host-parasite interactions. A common trend reflects a limited sequence homology between cysteine proteases and their inhibitors. The inhibitors are also known to participate in other housekeeping functions of the parasites. Generalizations about their roles are thus best avoided. In this review, the reader will find comprehensive information on the cellular localization of inhibitors of cysteine proteases, their structure, function, and the associated mechanisms of action. The reader will also find a thorough analysis of the role of these inhibitors in parasite pathology and the common trends interlinking them with parasite biology and evolution.
查看更多>>摘要：Acinetobacter baumannii is an important nosocomial and opportunistic pathogen. It causes infections worldwide, especially in intensive care units. It is clinically significant owing to its ability to persist for long periods on surfaces, as well as its resistance to multiple antibiotics. This pathogen has been reported to defy the available therapeutic options to combat it. In this dire circumstance, the need for new approaches to treating A. baumannii infections is undeniable. In this minireview, we summarize three important treatment options for controlling A. baumannii pathogen, including the use of bacteriophage / bacteriophage cocktails, phage-antibiotic combinations and resistance-driven fitness losses. It is hoped that, as resources to treat its infection expand, A. baumannii can become less scary.
查看更多>>摘要：The human oral cavity harbours complex microbial communities with various commensal microorganisms that play pivotal roles in maintaining host health and immunity but can elicit local and systemic diseases. The role of commensal microorganisms in SARS-CoV-2 infection and disease susceptibility and enrichment of opportunistic pathobionts in the oral cavity is poorly understood. The present study aims to understand the altered landscape of the oral microbiome and mycobiome in SARS-CoV-2 infected patients (n = 30) and its correlation with risk factors compared to non-infected individuals (n = 24) using targeted amplicon sequencing. Diminution of species richness, an elevated abundance of opportunistic pathogens (Veillonella, Acinetobacter, Klebsiella, Prevotella, Gemella, and Streptococcus) and impaired metabolic pathways were observed in the COVID-19 patients. Similarly, altered oral mycobiome with enrichment of known respiratory disease causing pathogenic fungi were observed in the infected individuals. The data further suggested that reduction in immunomodulatory microorganisms lowers the protection of individuals from SARS-CoV-2. Linear discriminant analysis identified several differentially abundant taxa associated with risk factors (ageing and co-morbidities). We also observed distinct bacterial and fungal community structures of elderly infected patients compared to the younger age group members making them highly vulnerable to SARS-CoV-2 infection and disease severity. Furthermore, we also assessed the dynamics of the oral microbiome and mycobiome in symptomatic and asymptomatic patients, host types, comorbidities, and viral load in the augmentation of specific pathobionts. Overall, the present study demonstrates the microbiome and mycobiome profiling of the COVID-19 infected individuals, the data further suggests that the SARS-CoV-2 infection triggers the prevalence of specific pathobiont.
Su, ZhenheLiu, XiaomengGuo, QinggangXuan, Lifeng...
10页
查看更多>>摘要：Pectobacterium spp. are causative agents of blackleg and soft rot of potato. However, little is known about the relationship between the pathogenicity of mixed infections of different Pectobacterium spp. at different temperatures. In this study, two pectinolytic strains of Pectobacterium spp. were isolated from the same potato plant with typical symptoms of blackleg and identified as P. brasiliense and P. carotovorum by multilocus sequence analysis (MLSA), whole-genome phylogenetic tree construction, average nucleotide identity (ANI) analysis and digital DNA-DNA hybridization (dDDH). Plant cell wall degrading enzyme, including pectinases, cellulases and proteases, as the most important virulence factors, as well as pathogenicity toward potato tuber, were compared between the strains P. brasiliense BL-2 and P. carotovorum BL-4 at 28 celcius. The results showed that P. carotovorum had higher cell wall-degrading enzyme activities and brought more severe disease symptoms to potato tubers than P. brasiliense. Moreover, the pathogenicity of P. carotovorum and P. brasiliense increased with increasing temperature (20, 25, 28, 32 celcius). The pathogenicity was more severe when P. carotovorum strain BL-4 was coinoculated with P. brasiliense strain BL-2, especially when the former exhibited an advantage in bacterial number at the initial time. The results of this study provide new insight for understanding the pathogenicity caused by mixed infections with different species of Pectobacterium spp., and they may provide some guidance for controlling potato blackleg and soft rot.
查看更多>>摘要：In light of spreading antibiotic resistance among pathogenic bacteria, the development of novel approaches to combat such microorganisms is crucial. Salmonella enterica is pathogenic to humans, however, it can also infect poultry, being a potential foodborne pathogen when poultry-derived food is contaminated by this bacterium. Phage therapy is one of the alternative ways to treat Salmonella-infected animals while the establishment of this method and its introduction to a general practice requires detailed studies on safety and efficacy. Here, we present the results of such studies with two previously isolated and characterized bacteriophages, vB_SenM2 and vB_Sen-TO17, and four strains of S. enterica belonging to two serovars, Typhimurium and Enteritidis. We demonstrated effective reduction of bacterial cell number and cell culture density when using each phage alone, and in combination (as a cocktail). These phages were also effective in reducing bacterial biofilm. The efficacy of this in vitro phage therapy was compared to the action of known antibiotics, as was the efficiency of appearance of bacteria resistant to both these types of antibacterial agents. Safety of the use of bacteriophages was demonstrated using the LAL chromogenic test and the chicken fibroblast viability assay. Finally, the efficacy of phage therapy was assessed with the in vivo model of S. enterica-infected Galleria mellonella larvae, showing a significant improvement in the survival of the animals. In conclusion, we demonstrated high efficacy and acceptable safety profiles of phage therapy against S. enterica strains using vB_SenM-2 and vB_Sen-TO17 phages (both alone and in a cocktail). These results open a possibility for a trial with the use of poultry and these phages which might potentially allow to introduce of this method for practical use in poultry farming.
查看更多>>摘要：Secondary metabolites of microbial origin are structurally diverse and functionally versatile compounds that offer selective advantages to the producing organism. Production of these compounds is low under natural conditions and requires elicitation for large-scale production. Omic sciences provide a major breakthrough in the discovery of novel compounds and indicate efficiency of microorganisms to produce a diverse array of chemical entities more than those known today. Synthetic biology in particular, has remarkably changed the outlook to explore natural products by unravelling hidden potential of the microorganisms. In silico studies pave a path to investigate new secondary metabolic compounds by the fusion of genetics, chemistry, and computer science, which expand their diversity and lead to generation of new analogs. Genes involved in secondary metabolite biosynthesis, regulation and transport in microorganisms are organized into clusters known as Biosynthetic gene clusters (BGCs). Application of sophisticated tools helps to get more information on newer BGCs leading to novel bioactive compound discovery. Experimental verification and structural elucidation are still the bottleneck in the discovery of a new product, but in silico tools help to speed up the process of product prediction and its identification. They also help in optimizing strains for stable and optimal production during scale up process for an economic output. In the present study, we have described microbial secondary metabolites with special mention of polyketides (PKS) and non-ribosomal polypeptides (NRPS) along with some of the strategies employed to induce their production, providing the main emphasis on in silico methods and tools used in their study and analysis to date.
Gomes, Ana Julia P. S.Viana, Gustavo H. R.Soares, Adriana C.Ferreira, Jaqueline M. S....
13页
查看更多>>摘要：Staphylococcus aureus is a Gram-positive bacterium responsible for a wide variety of infectious diseases, and its methicillin-resistant isolates pose a serious worldwide public health risk. New drugs are urgently needed for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections. Here, we evaluated the antibacterial activity of five 3-alkyl-pyridinic analogs against MRSA and, of these compounds, compound 6 showed promising antibacterial activity against Staphylococcus with minimum inhibitory concentration (MIC) ranging from 0.98 to 3.9 mu gmL(-1) . In addition, it exhibited a rapid bactericidal action, with complete elimination of MRSA after 6 h of incubation at 15.6 mu gmL(-1) . Compound 6 had the ability to damage the bacterial membrane and induce cell lysis and, due to its action on the membrane, showed low resistance induction potential in vitro. In the combination study, compound 6 revealed an additive effect (FICI = 1) with vancomycin and ofloxacin and ciprofloxacin (FICI = 0.75) against MRSA, reducing the effective concentration of this antibiotic two-fold. The anti-staphylococcal activity of compound 6 was stable in the presence of different concentrations of NaCl (50, 200, and 400 mu M), trypsin ( 1:500, 1:250) and under a variety of pH values (4, 5, 6, and 8); however, its binding to plasmatic proteins (i.e., albumin) was substantial. The previous exposure of MRSA to the compound was able to reduce the formation of bacterial biofilm and reduce the biomass of mature biofilms. Compound 6 showed low selectivity in vitro for MRSA USA 300 when compared to eukaryotic cells (epithelial, fibroblast, and red blood cells).
NSTL
Elsevier