Anti-Infective Agents - Volume 20, Issue 1, 2022

During the second wave of Covid-19 in India, doctors recently reported a outbreak of cases involving a rare infection-called the “black fungus”-among recovering and recovered Covid-19 patients. The frequency of bacterial and fungal coinfections has been continuously rising. At the same time, invasive pulmonary aspergillosis is increasingly being recognized in association with nCOVID-19. Currently, India is suffering from a newly maiming disease associated with nCOVID-19 infected patients; at the time of the treatment, it can be developed into rhino-orbital mucormycosis. There are some approved antifungal therapies for treating this fungal infection. The background, risk factors, and associated reports about the infection are described in this review.

Background: The Kingdom (Fungi) comprises numerous species that are associated with numerous fungal diseases. Moreover, the fungal resistance, stagnation in the development of antifungal agents and unacceptably high mortality rate associated with some resistant fungus indicate that alternative therapeutic options should be considered. Objective: The objective of this study was to find out new therapeutic targets of A.fumigatus in response to adjunctive combination, i.e., Ketoconazole (KTZ) plus EDTA. Methods: A.fumigatus was cultured in the absence and presence of a sublethal dose (MIC 50) of EDTA, KTZ and a combination of KTZ plus EDTA. The cytosolic proteins were extracted by mechanical grinding of fungal cells. The protein profile was studied by using a proteomic approach and the identification of protein was done by MALDI-TOF/MS. The morphological effect of the combination on A. fumigatus was studied by Scanning Electron Microscopy (SEM) and toxic effect on erythrocytes by haemolytic assay. Results: The combination of KTZ with EDTA was non-toxic up to 500 μg/ml by MTT assay. It inhibits the expression of the following proteins: Glutamatedehydrogenase, Phenyl alanyl t-RNA synthetase POD G, CaO19-5601, AN6454.2 (Conserved domain; MFS (Major Facilitator Superfamily), serine/threonine-protein kinase and dipeptidyl peptidase (identified by peptide mass fingerprinting). Some of these proteins are involved in hyphal development. Morphological defects on the development of fungus (like disrupted hyphal tips, phialide) were observed. Conclusion: These targets can be used for novel drug development as some of them are involved in fungal virulence, and adjunctive combination therapy can be an optimistic approach.

Introduction: Natural products or phytochemicals have always been useful as effective therapeutics providing the lead for rational drug discovery approaches in specific to anti-viral therapeutics. Methods: The ongoing pandemic caused by novel coronavirus has created a demand for effective therapeutics. Thus, to achieve the primary objective to search for effective anti-viral therapeutics, in silico screening of phytochemicals present in the extract of Curcuma longa (ex. Curcumin) has been planned. Results: The present work involves the evaluation of ADME properties and molecular docking studies. Conclusion: The application of rationalized drug discovery approaches to screen the diverse natural resources will speed up the anti-COVID drug discovery efforts and benefit the global community.

Aim: The present study was designed to synthesize novel Schiff bases and their metal complexes with promising antimicrobial and anti-angiogenic potential. Background: Currently, drug resistance has been seen in a diverse range of microbes, which is considered a major threat to widespread infectious diseases. Therefore, it is essential to investigate novel therapeutic molecules with broad-spectrum activities. Methods: The novel Schiff base ligands were synthesized by using a condensation reaction of ethylenediamine with p-chloroacetanilide and p-bromoactanilide. Fe(III), Ni(II), Mn(II), and Co(II) metal complexes were prepared by refluxing the ligand with respective metal chloride salts in a 2:1 molar ratio. Results: Structures of the synthesized compounds were characterized by IR, 1H NMR, UV-VIS, and mass spectrometry. Anti-microbial activities of all the synthesized compounds were determined against bacterial strains (S. aureus and K. pneumoniae) and fungal strains (A. niger and Trichophyton rubrum) by using the well plate diffusion method. DNA photo-cleavage and anti-angiogenic properties were evaluated by gel electrophoresis and CAM assay, respectively. Molecular docking studies were performed to analyze the binding interactions of synthesized compounds with topoisomerase II alpha. Conclusion: The present preliminary efforts may be helpful to design novel drugs with therapeutic potential.

Background: Dermatophytes are well-known fungus having the capability to invade keratinized tissues of nails, skin, and hair, of humans and other animals, causing dermatophytosis. Citrullus lanatus (watermelon) seed is a rich source of vitamin E, essential fatty acids, and minerals, bearing various health benefits. Despite the presence of many useful components, the oil is not much explored. Accordingly, the study was planned to investigate the fatty acid profiling, in vitro antioxidant, anti-inflammatory, and potential antidermatophytic activity of Citrullus lanatus seed oil against dermatophytic strains. Methods: The C. lanatus oil was extracted from seeds, and fatty acid profiling was characterized by GC-MS. Further, the oil was subjected to DPPH scavenging activity, and the anti-inflammatory activity was evaluated from Bovine serum albumin assay. The antidermatophytic screening against Microsporum canis, Trichophyton rubrum, and Trichophyton mentagrophytes was carried out by agar well diffusion, broth microdilution assay, and growth kinetics assay. Results: The C. lanatus seed oil exhibited good antioxidant activity close to ascorbic acid, i.e., IC50- 52.22 μg/ml, 35.72 μg/ml, respectively, and the oil exhibited moderate anti-inflammatory activity (315.2 μg/ml) as that of the standard drug diclofenac sodium (174.3μg/ml). The fatty acid profiling indicates the presence of eight main compounds, out of which ç-tocopherol, butylated hydroxytoluene, and hexadecanoic acid are predominantly present. The C. lanatus seed oil showed promising activity against T. rubrum with a lower minimum inhibitory concentration value with respect to positive controls, Fluconazole and Ketoconazole. The oil also had a strong effect on timedependent kinetic inhibition against T. rubrum. This was the first report of C. lanatus seed oil against any dermatophyte. Conclusion: In conclusion, the study supports the exploitation of C. lanatus seed oil and its main compounds as a source of natural antioxidants, anti-inflammatory, and as a novel agent against dermatophytes for curing superficial fungal infections in the near future.

Background: Coagulase-negative Staphylococci (CoNS) is one of the major causes of infections in hospitals. Methicillin resistance has greatly increased in different CoNS species in previous years. Here, we evaluated the performance of four phenotypic tests for detecting mecA-mediated methicillin resistance rate in CoNS isolated from different device-associated infections in Tanta University Hospitals, Egypt. Methodology: One hundred and fifteen CoNS isolates were examined for mecA-mediated methicillin resistance using polymerase chain reaction (PCR) as the standard gold test. Susceptibility to methicillin was investigated using VITEK 2 assay, oxacillin broth microdilution, and cefoxitin disc diffusion tests. Results: Of all isolates, 98.3% were mecA-positive. The sensitivities of the different methods examined were as follows: 100% for the VITEK cefoxitin test, 97.4% for the VITEK oxacillin test, 93.8% for the oxacillin broth microdilution, and 82.3% for the cefoxitin disc diffusion test. The test specificity could not be accurately determined because of the small number of mecA-negative isolates (n = 2). Conclusion: The rate of methicillin resistance reached 98.3% among CoNS isolates. Our results demonstrate that the VITEK 2 assay is rapid and has high sensitivity compared to other phenotypic methods for detecting methicillin resistance among different species of CoNS. Therefore, we recommend the dual measurement of both cefoxitin and oxacillin susceptibilities using the VITEK 2 assay for best results.