Cocktailed fragment screening by X-ray crystallography of the antibacterial target undecaprenyl pyrophosphate synthase from Acinetobacter baumannii

Direct soaking of protein crystals with small-molecule fragments grouped into complementary clusters is a useful technique when assessing the potential of a new crystal system to support structure-guided drug discovery. It provides a robustness check prior to any extensive crystal screening, a double check for assay binding cutoffs and structural data for binding pockets that may or may not be picked out in assay measurements. The structural output from this technique for three novel fragment molecules identified to bind to the antibacterial target Acinetobacter baumannii undecaprenyl pyrophosphate synthase are reported, and the different physicochemical requirements of a successful antibiotic are compared with traditional medicines.
Source: Acta Crystallographica Section F - Category: Biochemistry Authors: Tags: undecaprenyl pyrophosphate synthase fragment screening Acinetobacter baumannii research communications Source Type: research

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Authors: Cai W, Kesavan DK, Cheng J, Vasudevan A, Wang H, Wan J, Abdelaziz MH, Su Z, Wang S, Xu H Abstract Acinetobacter baumannii, as a nonfermentation Gram-negative bacterium, mainly cause nosocomial infections in critically ill patients. With the widespread of multidrug-resistant Acinetobacter baumannii, the urgency of developing effective therapy options has been emphasized nowadays. Outer membrane vesicles derived from bacteria show potential vaccine effects against bacterial infection in recent study. Our present research is aimed at investigating the mechanisms involved in immune protection of mice after out...
Source: Journal of Immunology Research - Category: Allergy & Immunology Tags: J Immunol Res Source Type: research
Publication date: 20 February 2020Source: Cell, Volume 180, Issue 4Author(s): Jonathan M. Stokes, Kevin Yang, Kyle Swanson, Wengong Jin, Andres Cubillos-Ruiz, Nina M. Donghia, Craig R. MacNair, Shawn French, Lindsey A. Carfrae, Zohar Bloom-Ackerman, Victoria M. Tran, Anush Chiappino-Pepe, Ahmed H. Badran, Ian W. Andrews, Emma J. Chory, George M. Church, Eric D. Brown, Tommi S. Jaakkola, Regina Barzilay, James J. CollinsSummaryDue to the rapid emergence of antibiotic-resistant bacteria, there is a growing need to discover new antibiotics. To address this challenge, we trained a deep neural network capable of predicting mole...
Source: Cell - Category: Cytology Source Type: research
Interleukin-10 plays important, yet contrasting, roles in host protection against bacterial infections and in the septic response. To determine the role of IL-10 in the host defense against Acinetobacter baumannii infection, wild-type (WT) and IL-10-deficient mice were infected intranasally with the bacteria. IL-10-deficient mice exhibited increased mortality, severe pathology, and excess production of proinflammatory cytokines and chemokines in the lungs, and increased bacterial burdens in bronchoalveolar lavage (BAL) fluids and lung homogenates after A. baumannii infection, compared to WT mice. Intranasal administration ...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
In this study we designed and synthetized various derivatives of NCR247, including shorter fragments and various chimeric derivatives. The antimicrobial activity of these peptides was tested on the ESKAPE bacteria; Enterococcus faecalis, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Escherichia coli as a member of Enterobacteriaceae and in addition Listeria monocytogenes and Salmonella enterica. The 12 amino acid long C-terminal half of NCR247, NCR247C partially retained the antimicrobial activity and preserved the multitarget interactions with partners of NCR247. Nevert...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
Publication date: Available online 20 February 2020Source: Journal of Bioscience and BioengineeringAuthor(s): Linshu Jiao, Huibing Chi, Zhaoxin Lu, Chong Zhang, Shir Reen Chia, Pau Loke Show, Yang Tao, Fengxia Lul-Asparaginases have the potential to inhibit the formation of acrylamide, a harmful toxin formed during high temperature processing of food. A novel bacterium which produces l-asparaginase was screened. Type I l-asparaginase gene from Acinetobacter soli was cloned and expressed in Escherichia coli. The recombinant l-asparaginase had an activity of 42.0 IU mL−1 and showed no activity toward l-glutamine and d-...
Source: Journal of Bioscience and Bioengineering - Category: Biomedical Science Source Type: research
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Source: Annals of Laboratory Medicine - Category: Laboratory Medicine Tags: Ann Lab Med Source Type: research
Acinetobacter baumannii is an emerging opportunistic pathogen that primarily infects critically ill patients in nosocomial settings. Because of its rapid acquisition of antibiotic resistance, infections caused by A. baumannii have become extremely difficult to treat, underlying the importance of identifying new antimicrobial targets for this pathogen. Manganese (Mn) is an essential nutrient metal required for a number of bacterial processes, including the response to oxidative stress. Here, we show that exogenous Mn can restore A. baumannii viability in the presence of reactive oxygen species (ROS). This restoration is not...
Source: Infection and Immunity - Category: Infectious Diseases Authors: Tags: Molecular Pathogenesis Source Type: research
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Source: Current Pharmaceutical Biotechnology - Category: Biotechnology Authors: Tags: Curr Pharm Biotechnol Source Type: research
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Source: Journal of Global Antimicrobial Resistance - Category: Infectious Diseases Source Type: research
Conclusion: Intubated patients with multidrug-resistant, COS infections have a longer stay in ICU than non-COS patients. COS infections associated with bacteremia have high mortality.
Source: Journal of Global Infectious Diseases - Category: Infectious Diseases Authors: Source Type: research
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