RESUMEN
BACKGROUND: The emergence of multidrug-resistant pathogens and the lack of new antimicrobial drugs is a major public health concern that needs urgent and innovative solutions. Endophytic fungi living in unique niches such as in endosymbiosis with plants are increasingly drawing attention as alternative sources of novel and chemically diverse compounds with unique mechanisms of action. METHODS: In the present study, ten endophytic fungi isolated from the medicinal plant, Sclerocarya birrea were screened for bioactivity against a panel of indicator bacteria. Three bioactive endophytic fungi (strains P02PL2, P02MS1, and P02MS2A) were selected and identified through ITS-rDNA sequencing. The whole broth extracts of the three selected isolates were further screened against contemporary drug-resistant bacterial pathogens. This was followed by partial purification by solid phase extraction and GC-MS analysis of bioactive fractions. RESULTS: The bioactive endophytic fungi were identified as Alternaria alternata species (strains P02PL2 and P02MS1) and Nigrospora oryzae (strain P02MS2A). The whole broth extracts from N. oryzae P02MS2A exhibited a MIC of one µg/mL and 16 µg/mL against gram-negative, MDR Pseudomonas 5625574 and gram-positive MRSA 25775 clinical isolates, respectively. After partial purification and GC-MS analysis of whole broth extract from A. alternaria PO2MS1, 2-fluorobenzoic acid heptadecyl was putatively identified as the active compound in fraction C of this extract. This compound was also putatively identified in fraction E of A. alternata P02PL2, fraction B of A. alternata P02MS1 and fraction B of N. oryzae P02MS2A, and interestingly, all these fractions retained activity against the two MDR clinical isolates. CONCLUSION: The putative identification of 2-fluorobenzoic acid heptadecyl compound showing a broad-spectrum of activity, more especially against gram-negative MDR contemporary pathogens is highly encouraging in the initiative at developing novel drugs to combat multi-drug resistance.
Asunto(s)
Alternaria , Extractos VegetalesRESUMEN
The increasing reports of multidrug-resistant Klebsiella pneumoniae have emerged as a public health concern, raising questions about the potential routes for the evolution and dissemination of the pathogenic K. pneumoniae into environmental reservoirs. Potential drivers of the increased incidence of antimicrobial-resistant environmental K. pneumoniae include the eminent global climatic variations as a direct or indirect effect of human activities. The ability of microorganisms to adapt and grow at an exponential rate facilitates the distribution of environmental strains with acquired resistant mutations into water systems, vegetation, and soil which are major intersection points with animals and humans. The bacterial pathogen, K. pneumoniae, is one of the critical-priority pathogens listed by the World Health Organization, mostly associated with hospital-acquired infections. However, the increasing prevalence of pathogenic environmental strains with similar characteristics to clinical-antibiotic-resistant K. pneumoniae isolates is concerning. Considering the eminent impact of global climatic variations in the spread and dissemination of multidrug-resistant bacteria, in this review, we closely assess factors influencing the dissemination of this pathogen resulting in increased interaction with the environment, human beings, and animals. We also look at the recent developments in rapid detection techniques as part of the response measures to improve surveillance and preparedness for potential outbreaks. Furthermore, we discuss alternative treatment strategies that include secondary metabolites such as biosurfactants and plant extracts with high antimicrobial properties.
RESUMEN
The continuous burden of human immunodeficiency virus-1 in Sub-Saharan Africa, coupled with the inability of antiretroviral agents to eradicate HIV-1 from viral reservoirs, the potential risks of drug resistance development, and the development of adverse effects, emphasizes the need to develop a new class of HIV-1 inhibitors. Here, we cultivated four endophytic fungal isolates from a medicinal plant, Albizia adianthifolia with the addition of small epigenetic modifiers, sodium butyrate, and valproic acid, to induce the expression of biosynthetic gene clusters encoding active secondary metabolites with probable anti-HIV activities. We identified a non-toxic crude extract of the endophytic fungus Penicillium chrysogenum treated with sodium butyrate to possess significantly greater anti-HIV activity than the untreated extracts. Penicillium chrysogenum P03MB2 showed anti-HIV activity with an IC50 of 0.6024 µg/mL compared to untreated fungal crude extract (IC50 5.053 µg/mL) when treated with sodium butyrate. The profile of secondary metabolite compounds from the bioactive, partially purified extracts were identified by gas chromatography-mass spectrometry (GC-MS), and more bioactive compounds were detected in treated P. chrysogenum P03MB2 fractions than in untreated fractions. Pyrrolo[1,2-a]pyrazine-1,4-dione, hexahydro (13.64%), cyclotrisiloxane, hexamethyl (8.18%), cyclotetrasiloxane, octamethyl (7.23%), cyclopentasiloxane, decamethyl (6.36%), quinoline, 1,2-dihydro-2,24-trimethyl (5.45%), propanenitrile (4.55%), deca-6,9-diene (4.55%), dibutyl phthalate (4.55%), and silane[1,1-dimethyl-2-propenyl)oxy]dimethyl (2.73%) were the most abundant compounds. These results indicate that treatment of endophytic fungi with small epigenetic modifiers enhances the secretion of secondary metabolites with stronger anti-HIV-1 properties, acknowledging the feasibility of epigenetic modification as an innovative approach for the discovery of cryptic fungal metabolites which can be developed into therapeutic compounds.