Rhizobacterial mediated antimetabolites and their significant effect on human pathogens

Background: The emergence of antibiotic resistant bacteria is increasing globally. Therefore, new strategies and exploration of new metabolites are need of the day to combat various diseases.  The aim of the current study is to isolate the rhizobacterial strains from medicinal plants to examine their antibacterial activity against human pathogens.Methods: The total 239 rhizobacterial isolates were screened with agar plug and well diffusion methods, characterized biochemically and identified by Bergey’s manual scheme. In chemical screening, metabolic extracts of rhizobacterial isolates were separated in thin layer chromatography (TLC) and further identified by HPLC. The ability of rhizobacterial strains for optimum metabolite production was checked in vitro under different environmental conditions.Results: Results showed that 31% isolates had antibacterial activity against Bacillus cereus, Bacillus subtilis, E. coccus, E. coli, Salmonella, Klebsiella, Staphylococcus aureus ATCC20737, Staphylococcus aureus ATCC25923 and Neisseria. Gonorrhea ATCC19424, methicillin resistant Staphylococcus aureus 1, methicillin resistant Staphylococcus aureus 6 and methicillin resistant Staphylococcus aureus 8.  Maximum rhizobacterial strains showed best antibacterial activity at 35ᵒC and at pH7. ST5 strain showed significant results against E. coli ETCC and methicillin resistant Staphylococcus aureus-7 (25mm zone of inhibition). The bands of ST5 and ST2 extracts on a TLC plate were detected at Rf value 4.7 and 4.8 respectively. In HPLC, different peaks at different retention times with maximum peak at 2.90 and 2.92 indicating the production of antimetabolites.Conclusion: These rhizobacterial isolates are valuable inputs in natural consortium to produce specific antibacterial metabolites. Demonstrating the structure and purification of these bioactive compounds may enhance the antimicrobial activities which further can be helpful in development of antibiotics.Keywords: Antibiotics; Rhizobacteria; Antimicrobial agents; MRSA; HPL

Assessment of Antimicrobial Competence of Epiphytes and Endophytes from Osmium basilicum and Trigonella foenum graecum

Plant-associated bacteria are an unexplored group of microorganisms that has enormous potential. These bacteria are the source of finding new antimicrobial substances. The present study aimed to isolate and characterize the epiphytes and endophytes from Osmium basilicum and Trigonella foenum graecum plants and to determine their antimicrobial potential against pathogenic bacteria from Nishtar Hospital Multan, Pakistan. The sum of 18 stems and roots along leaf specimens were assembled as of the plant\u27s Osmium basilicum plus Trigonella foenum graecum as of the distinct locales of the Multan city. Overall 73 bacterial strains were isolated and their colony morphology, gram staining, spore staining, and characterization were done. Further 10 epiphytic strains and 14 endophytic strains were selected based on their antimicrobial potential intended for a thorough examination. The activity of the selected microbial isolates was determined against pathogenic bacteria K.pneumoniae, MRSA, E.coli, S .aureus, S.typhimurium as of Nishtar hospital. Out of all strains, only one epiphytic and two endophytic bacterial isolates (methanolic extracts) (obr, obl3, and tfen2 were isolated from root, leaf, and root of Osmium basilicum and Trigonella foenum graecum correspondingly inhibited altogether gram-positive besides gram-negative pathogenic microbes involved in this investigation. The hunt to find novel compounds from plant bacteria will open new horizons in the industrial and agricultural sectors

Emergence of SARS-CoV-2: Insight in genomics to possible therapeutics

Rising of a new virus from city of Cathay, responsible for 2019 global pandemic is caused by SARS-CoV-2marked as a great threat for populations. The member (CoV-2) from vast family of Covid virus with single- stranded RNA spread to over 216 countries and billions of individuals died all around the globe. Regardless of all strict standard operating procedures, special care and therapies, SARS-CoV-2 mutating its genomic structure and leads to shutting the world. While different therapeutic approaches face problems due to the complexity in pathogenicity mechanism of CoV-2 and its variants. Mechanism of action, genome analysis, transmission, development of broad-spectrum antiviral medications and SARS-CoV-2 vaccines have been reported which are essential for future directions to control this pandemic. Here, in this review, these domains were discussed to highlight the genome structure pathophysiology, immune response, multiple diagnostic methods, and possible treatment strategies. This review deliberates the methodologies for creating practical vaccinations and treatment cocktail to manage this eruption.Keywords: SARS-CoV-2; Genetics; Epidemiology   

Estimation of Genetic Divergence in 40 Elite Cotton Germplasm

Background: Identification and development of superior cotton genotypes and their further improvement has been one of the primitive aims of plant breeding programmers. Therefore, necessity of analyzing the agro-morphological and yield attributes of advanced lines of cotton is doubtless.Methods: Mean performance and correlation between ten different morphological, yield and fiber related attributes of forty cotton genotypes from all over the Pakistan under National Coordinated Varietal Trial were studied at Central Cotton Research Institute of Multan. Selected traits included several sympodial and monopodial branches, plant height, number of bolls per plant, staple length, seed cotton yield, boll weight, fiber strength, percentage ginning out turn and micronaire value.Results: Statistical analysis of variance disclosed highly significant (p<0.01) differences among all cotton genotypes for majority of the characteristics. Basic descriptive statistical analysis of selected agronomic traits revealed the presence of substantial genetic variation among 40 genotypes of cotton for 10 selected traits. The correlation coefficient was determined both at p<0.05 and p<0.01 levels and the observations demonstrated that some of the characteristics exhibited positive correlation, while others displayed negative correlation with each other. Micronaire showed highly significant positive association with percentage ginning out turn (0.3412) and boll weight (0.2421 g) as well as highly significant negative association with fiber strength (-0.5973).Conclusion: Convincingly, mean performances and correlation of different traits with one another can be utilized in cotton breeding programs in future to improve the yield of cotton seed and to select fiber related attributes with desired characteristics.Keywords: Gossypium hirsutum; Morphological agronomic traits; Statistical analysi

Status and diversity of coastal avian fauna in Gwadar peninsula, Balochistan

The 1050 km long coastline of Pakistan, extends from Sir Creek in the southeast of Indus delta to Gwadar Bay in the west. This article is based on diversity, habitat, status and distribution of different species of coastal birds present in the Gwadar coast. Observation of birds was done during winter season at four different sites. The habitat is important for different coastal birds like terns, gulls, pelicans and waders including resident and migratory species. A total of 55 species were recorded from the entire area. The species richness was higher at two sites. The birds were seen in higher numbers at uninhabited points compared to those near the populated area or the port. Shannon diversity index for bird community was calculated for four sites namely Shabi Estuary, Gwadar East Bay, Gwadar West Bay and Gurab, where the diversity was found to be 2.82, 2.27, 2.33 and 2.40 respectively. Birds of Common Sandpiper (Actitishy poleucos), Common Teal (Anas crecca), Wigeon (Anas Penelope), Shoveller (Anas clypeata), Pochard (Aythya ferina), Common Coot (Fulica atra), Grey Plover (Pluvialis squatarola), Kentish Plover (Charadrius alexandriunus), Dusk Red Shank (Tringa erythropus) and Great White Pelicans (Pelecanus onocrotalus) have been recorded in large numbers during the study period. Some vulnerable species for e.g. Pochard (Aythya ferina) and endangered species for e.g. Great Knot (Calidris tenuirostris), Egyptian Vulture (Neophron percnopterus), and two near threatened species Oyster catcher (Haematus ostralegus) and Dalmation Pelican (Pelecanus crispus) were also recorded. The major threats to the ecosystem are habitat degradation due to port construction, urbanization, hunting, poaching and other anthropogenic activities

Parmotrema cooperi中的新型抗醣化物质和酶抑制剂(英文)

通讯作者, E-mail: [email protected]地衣是被广泛用于传统药物中的独特个体.本文对一类地衣,Parmotrema cooperi,进行了生物测定引导的植物化学研究和生物活性评价.对该类地衣的首次生物测定引导的化学研究分离出了化合物ethyl heamatomate(1),atraric acid(2),ethyl orsellinate(3),orsellinic acid(4),lecanoric acid(5),gyrophoric acid(6)以及licanorin(7).化合物1～7的结构主要通过一维、二维核磁共振谱和质谱等谱学方法判定.对这些化合物还进行了抗醣化活性以及尿素酶、α-胰凝乳蛋白酶、β-葡萄糖醛酸苷酶抑制活性的评价.这些苯酚化合物没有显示特别好的活性,但其中大部分对蛋白质醣化和尿素酶活性具有较好的抑制作用

Biodeterioration of Microplastics: A Promising Step towards Plastics Waste Management

Polyethylene and Polyester materials are resistant to degradation and a significant source of microplastics pollution, which is an emerging concern. In the present study, the potential of a dumped site bacterial community was evaluated. After primary screening, it was observed that 68.5% were linear low-density polyethylene, 33.3% were high-density, and 12.9% were Polyester degraders. Five strains were chosen for secondary screening, in which they were monitored by FTIR, SEM and weight loss degradation trials. Major results were observed for Alcaligenes faecalis (MK517568) and Bacillus cereus (MK517567), as they showed the highest degradation activity. Alcaligenes faecalis (MK517568) degrades LLDPE by 3.5%, HDPE by 5.8% and Polyester by 17.3%. Bacillus cereus (MK517567) is better tolerated at 30 °C and degrades Polyester by 29%. Changes in infrared spectra indicated degradation pathways of different strains depending on the types of plastics targeted. Through SEM analysis, groves, piths and holes were observed on the surface. These findings suggest that soil bacteria develop an effective mechanism for degradation of microplastics and beads that enables them to utilize plastics as a source of energy without the need for pre-treatments, which highlights the importance of these soil bacteria for the future of effective plastic waste management in a soil environment

In silico identification of potential inhibitors of key SARS-CoV-2 3CL hydrolase (Mpro) via molecular docking, MMGBSA predictive binding energy calculations, and molecular dynamics simulation

The incidence of 2019 novel corona virus (SARS-CoV-2) has created a medical emergency throughout the world. Various efforts have been made to develop the vaccine or effective treatments against the disease. The discovery of crystal structure of SARS-CoV-2 main protease has made the in silico identification of its inhibitors possible. Based on its critical role in viral replication, the viral protease can prove to be a promising “target” for antiviral drug therapy. We have systematically screened an in-house library of 15,754 natural and synthetic compounds, established at International Center for Chemical and Biological Sciences, University of Karachi. The in silico search for potential viral protease inhibitors resulted in nine top ranked ligands (compounds 1–9) against SARS-CoV-2 main protease (PDB ID: 6LU7) based on docking scores, and predictive binding energies. The in silico studies were updated via carrying out the docking, and predictive binding energy estimation, with a recently reported crystal structure of main protease (PDB ID: 6Y2F) at a better resolution i.e., 1.95 Å. Compound 2 (molecular bank code AAA396) was found to have highest negative binding energy of −71.63 kcal/mol for 6LU7. While compound 3 (molecular bank code AAD146) exhibited highest negative binding energy of -81.92 kcal/mol for 6Y2F. The stability of the compounds- in complex with viral protease was analyzed by Molecular Dynamics simulation studies, and was found to be stable over the course of 20 ns simulation time. Compound 2, and 3 were predicted to be the significant inhibitors of SARS-CoV-2 3CL hydrolase (Mpro) among the nine short listed compounds

Bio-Catalytic Structural Transformation of Anti-cancer Steroid, Drostanolone Enanthate with Cephalosporium aphidicola and Fusarium lini, and Cytotoxic Potential Evaluation of Its Metabolites against Certain Cancer Cell Lines

In search of selective and effective anti-cancer agents, eight metabolites of anti-cancer steroid, drostanolone enanthate (1), were synthesized via microbial biotransformation. Enzymes such as reductase, oxidase, dehydrogenase, and hydrolase from Cephalosporium aphidicola, and Fusarium lini were likely involved in the biotransformation of 1 into new metabolites at pH 7.0 and 26°C, yielding five new metabolites, 2α-methyl-3α,14α,17β-trihydroxy-5α-androstane (2), 2α-methyl-7α-hydroxy-5α-androstan-3,17-dione (3), 2-methylandrosta-11α-hydroxy-1, 4-diene-3,17-dione (6), 2-methylandrosta-14α-hydroxy-1,4-diene-3,17-dione (7), and 2-methyl-5α-androsta-7α-hydroxy-1-ene-3,17-dione (8), along with three known metabolites, 2α-methyl-3α,17β-dihydroxy-5α-androstane (4), 2-methylandrosta-1, 4-diene-3,17-dione (5), and 2α-methyl-5α-androsta-17β-hydroxy-3-one (9), on the basis of NMR, and HREI-MS data, and single-crystal X-ray diffraction techniques. Interestingly, C. aphidicola and F. lini were able to catalyze hydroxylation only at alpha positions of 1. Compounds 1–9 showed a varying degree of cytotoxicity against HeLa (human cervical carcinoma), PC3 (human prostate carcinoma), H460 (human lung cancer), and HCT116 (human colon cancer) cancer cell lines. Interestingly, metabolites 4 (IC50 = 49.5 ± 2.2 μM), 5 (IC50 = 39.8 ± 1.5 μM), 6 (IC50 = 40.7 ± 0.9 μM), 7 (IC50 = 43.9 ± 2.4 μM), 8 (IC50 = 19.6 ± 1.4 μM), and 9 (IC50 = 25.1 ± 1.6 μM) were found to be more active against HeLa cancer cell line than the substrate 1 (IC50 = 54.7 ± 1.6 μM). Similarly, metabolites 2 (IC50 = 84.6 ± 6.4 μM), 3 (IC50 = 68.1 ± 1.2 μM), 4 (IC50 = 60.4 ± 0.9 μM), 5 (IC50 = 84.0 ± 3.1 μM), 6 (IC50 = 58.4 ± 1.6 μM), 7 (IC50 = 59.1 ± 2.6 μM), 8 (IC50 = 51.8 ± 3.4 μM), and 9 (IC50 = 57.8 ± 3.2 μM) were identified as more active against PC-3 cancer cell line than the substrate 1 (IC50 = 96.2 ± 3.0 μM). Metabolite 9 (IC50 = 2.8 ± 0.2 μM) also showed potent anticancer activity against HCT116 cancer cell line than the substrate 1 (IC50 = 3.1 ± 3.2 μM). In addition, compounds 1–7 showed no cytotoxicity against 3T3 normal cell line, while compounds 8 (IC50 = 74.6 ± 3.7 μM), and 9 (IC50 = 62.1 ± 1.2 μM) were found to be weakly cytotoxic

Study of drug resistance-associated genetic mutations, and phylo-genetic analysis of HCV in the Province of Sindh, Pakistan

Abstract Current management of HCV infection is based on Direct-Acting Antiviral Drugs (DAAs). However, resistance-associated mutations, especially in the NS3 and NS5B regions are gradually decreasing the efficacy of DAAs. The aim of the current study was to identify such mutations in the NS3, and NS5B genes in DAAs treatment-naïve Pakistani chronic HCV 3a patients. Peripheral blood samples were collected from 233 chronic HCV 3a patients at different tertiary care hospitals in Karachi, Pakistan, between August 2020 to September 2021. PCR-amplified target regions of the NS3/NS5B gene were subjected to Sanger sequencing to identify resistance-associated mutations. Phylogenetic analysis of the identified amino acid sequences was performed using HCV3a sequences of the global population in the virus pathogen resource (VIPR) database. Sequence analysis identified five amino acid mutations, Leu36Pro, Gln41His, Gln80Lys/Arg, Ala156Tyr, and Gln168Arg in the NS3 region, and two mutations Leu159Phe and Cys316Arg in the NS5B region. Phylogenetic analysis revealed a high genetic diversity in the studied isolates. Overall, the prevalence of resistance-associated substitutions was almost similar to other geographic regions worldwide. This data could be helpful in selecting the most effective treatment regimen for HCV chronically infected people in Pakistan