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Background & objectives: Multidrug-resistant (MDR) Acinetobacter baumannii is a serious threat for human health worldwide. The studies on agents targeting A. baumannii are imperative due to identified A. baumannii co-infections in COVID-19. Bacteriophages are promising antibacterial agents against drug-resistant bacteria. This study intended to isolate bacteriophages against MDR A. baumannii from the water of river Ganga, to be used potentially as therapeutic and disinfectant particles. Methods: Acinetobacter phages were isolated from the Ganga water collected from Kanpur and further tested on 50 MDR A. baumannii isolates to determine host range. The phages were morphologically characterized by transmission electron microscopy. The disinfectant property of the isolated phages was tested by spraying of bacteriophage cocktail on MDR A. baumannii contaminated plastic surface, analyzed by colony-forming unit (CFU) and bioluminescence assay (adenosine triphosphate monitoring). Results: A total of seven bacteriophages were isolated against MDR A. baumannii. The bacteriophages lysed three MDR A. baumannii isolates out of 50 tested, showing narrow host range. Electron microscopy revealed hexagonal heads and long tails of bacteriophages, belonging to order Caudovirales. The bacteriophage cocktail reduced the MDR A. baumannii load efficiently on plastic surface, evidenced by reduction in CFUs and bioluminescence. Interpretation & conclusions: The findings of this study suggest that the isolated bacteriophages are potential lytic agents for MDR A. baumannii clinical isolates, and may be used as potential therapeutic agents as well as disinfectant to combat MDR A. baumannii with due consideration to phage host specificity, with further characterization. [ABSTRACT FROM AUTHOR]

Emerging evidence shows co-infection with atypical bacteria in coronavirus disease 2019 (COVID-19) patients. Respiratory illness caused by atypical bacteria such as Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella pneumophila may show overlapping manifestations and imaging features with COVID-19 causing clinical and laboratory diagnostic issues. We conducted a prospective study to identify co-infections with SARS-CoV-2 and atypical bacteria in an Indian tertiary hospital. From June 2020 to January 2021, a total of 194 patients with laboratoryconfirmed COVID-19 were also tested for atypical bacterial pathogens. For diagnosing M. pneumoniae, a real-time polymerase chain reaction (PCR) assay and serology (IgM ELISA) were performed. C. pneumoniae diagnosis was made based on IgM serology. L. pneumophila diagnosis was based on PCR or urinary antigen testing. Clinical and epidemiological features of SARS-CoV-2 and atypical bacteria-positive and -negative patient groups were compared. Of the 194 patients admitted with COVID-19, 17 (8.8%) were also diagnosed with M. pneumoniae (n = 10) or C. pneumoniae infection (n = 7). Confusion, headache, and bilateral infiltrate were found more frequently in the SARS CoV-2 and atypical bacteria co-infection group. Patients in the M. pneumoniae or C. pneumoniae co-infection group were more likely to develop ARDS, required ventilatory support, had a longer hospital length of stay, and higher fatality rate compared to patients with only SARS-CoV-2. Our report highlights co-infection with bacteria causing atypical pneumonia should be considered in patients with SARS-CoV-2 depending on the clinical context. Timely identification of co-existing pathogens can provide pathogen-targeted treatment and prevent fatal outcomes of patients infected with SARS-CoV-2 during the current pandemic. [ABSTRACT FROM AUTHOR]

Background: Extrapulmonary tuberculosis (EPTB), accounting for 10%–20% of all cases of tuberculosis (TB), is known to be determined by host immunity. However, the contribution of bacterial factors to the development of EPTB has not been studied extensively. Mycolic acids are predominant lipids constituting the cell wall of Mycobacterium tuberculosis, and keto-mycolic acid is involved in the synthesis of foamy macrophages that facilitate persistence of mycobacteria. Hence, the present study was performed to gain an insight into variable expression of mycolic acids in clinical isolates of M. tuberculosis under stress. Methods: Pansusceptible clinical isolates of M. tuberculosis from patients with lymph node TB (LNTB) (n = 10) and pulmonary TB (PTB) (n = 10) were subjected to sodium dodecyl sulfate (SDS) stress, and the expression of mycolic acid and its biosynthetic genes was compared. Any bias arising due to the genotype of the clinical isolates was ruled out by performing single-nucleotide polymorphism cluster grouping (SCG), wherein no significant difference was observed between the SCG of LNTB or PTB isolates. Results: The expression of α-mycolic acid during the exposure to SDS was high in 7/10 (70%) LNTB and 6/10 (60%) PTB isolates. Methoxy mycolic acid showed an increased expression in 7/10 (70%) LNTB isolates and 4/10 (40%) PTB isolates. Increased expression of keto-mycolic acid on exposure with SDS was observed in 8/10 (80%) M. tuberculosis LNTB and 3/10 (30%) PTB isolates. Similarly, the mycolic acid synthesis gene, fas, was upregulated more in LNTB isolates than PTB isolates in vitro and ex vivo. SCG 3a was the most common SCG observed in 40% (8/20) of the isolates, followed by SCG 3b in 30% (6/20) of the isolates. There was no significant difference between the SCG of LNTB or PTB isolates. Conclusion: The higher expression of keto-mycolic acid in LNTB as against PTB isolates may indicate better survival in LNTB isolates in the presence of stress. [ABSTRACT FROM AUTHOR]

Neuropilin-1 (NRP1) was first described as a receptor for the axon guidance molecule, Semaphorin3A, regulating the development of the nervous system. It was later shown that NRP1 is an isoform-specific receptor for vascular endothelial growth factor (VEGF), specifically VEGF165. Much interest has been placed on the role of the various VEGF isoforms in vascular biology. Here we report that blocking NRP1 function, using a recently described antibody that inhibits VEGF165 binding to NRP1, surprisingly reduces VEGF121-induced migration and sprout formation of endothelial cells. Intrigued by this observation, direct binding studies of NRP1 to various VEGF isoforms were performed. We show that VEGF121 binds directly to NRP1; however, unlike VEGF165, VEGF121 is not sufficient to bridge the NRP1·VEGFR2 complex. Additionally, we show that VEGFR2 enhances VEGF165, but not VEGF121 binding to NRP1. We propose a new model for NRP1 interactions with various VEGF isoforms. [ABSTRACT FROM AUTHOR]

The titled molecule 2-Amino-N-(2-chloro-6-methylphenyl)thiazole-5-carboxamide (ANMC) is a core of anticancer drug dasatinib (leukemia). Its derivatives exhibited bioactivity against breast cancer. Experimentally, the titled compound was described using NMR ( 1 H NMR and 13 C NMR), FTIR and UV-visible spectroscopy. The results were compared with the theoretical predictions, showing good agreement such as theoretical NH vibrations showed symmetric stretching and asymmetric stretching at 3429 and 3440 cm -1 respectively, λmax values appear at 305 nm for experimental and 307.75 nm for theoretical observations in acetone medium. Hirshfeld surface analysis well described the secondary internal and external interactions obtained like d norm and d i ranges -1.8551 to 1.4590 and 0.0918 to 2.6756 respectively. Comparing UV-visible spectra obtained in various solvents with the calculated TD-DFT results revealed minimal solvent effects. Molecular electrostatic potential (MEP) map and Fukui functions were employed, which indicated reactive sites of the molecule and the obtained order of nucleophilic reactivity was C16 > C2 > C8 > Cl1 > C22 > C21. The bioactivity profile probability of ANMC was theoretically explored by calculation of electrophilicity index and drug-likeness. Molecular docking of the ANMC molecule was performed with ten receptors to obtain the best ligand-protein interaction and the minimum binding energy obtained was -8.0 kcal/mol. Biomolecular stability of ANMC was investigated by Molecular Dynamic Simulation (MDS). And also the analysis of free energies showed strong interactions between the ligand and the protein., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)