Author: Monteiro, Gustavo Claro ; Fernandes, Philipe Oliveira ; Ottoni, Flaviano Melo ; Mota, Bruno Eduardo Fernandes ; Kronenberger, Thales ; Valli, Marilia ; Dos Santos, André Gonzaga ; Coutinho, Isabel Duarte ; de Oliveira, Renata Barbosa ; Alves, Ricardo José ; Dos Santos Júnior, Valtair Severino ; Maltarollo, Vinícius Gonçalves ; Dias, Anna Letícia Teotonio ; Pádua, Rodrigo Maia de ; Oda, Fernando Bombarda ; Sousa, Yamara Viana ; Verzola, Marina Mol Sena Andrade ; da Silva Bolzani, Vanderlan ; Andricopulo, Adriano Defini ; Sá Magalhães Serafim, Mateus

The application of computer-aided drug discovery (CADD) approaches has enabled the discovery of new antimicrobial therapeutic agents in the past. The high prevalence of methicillin-resistantStaphylococcus aureus(MRSA) strains promoted this pathogen to a high-priority pathogen for drug development. In this sense, modern CADD techniques can be valuable tools for the search for new antimicrobial agents. We employed a combination of a series of machine learning (ML) techniques to select and evaluate potential compounds with antibacterial activity against methicillin-susceptible S. aureus (MSSA) and MRSA strains. In the present study, we describe the antibacterial activity of six compounds against MSSA and MRSA reference (American Type Culture Collection (ATCC)) strains as well as two clinical strains of MRSA. These compounds showed minimal inhibitory concentrations (MIC) in the range from 12.5 to 200 μM against the different bacterial strains evaluated. Our results constitute relevant proven ML-workflow models to distinctively screen for novel MRSA antibiotics.

03 Apr 2022·Journal of Dermatological TreatmentQ4 · MEDICINE

Trends and risk factors in the antibiotic management of skin and soft tissue infections in the United States

Q4 · MEDICINE

Article

Author: Storandt, Michael H. ; Beal, James R. ; Sahmoun, Abe E. ; Walden, Christopher D.

OBJECTIVEThe aim of this study was to examine the trends and risk factors of antibiotic treatment for skin and soft tissue infections (SSTIs), in the United States.METHODSWe conducted a retrospective analysis of SSTIs visits utilizing the 2011-2016 National Ambulatory Medical Care Survey.RESULTSThere were over 43 million visits for SSTIs in the US. We found no association between antibiotic treatment and gender, age, race, insurance, region, and metropolitan statistical area. Methicillin-resistant Staphylococcus aureus (MRSA) antibiotics were prescribed at 34.8% of SSTI visits, methicillin-sensitive Staphylococcus aureus (MSSA) antibiotics at 27.5%, and other antibiotics at 21.7%. Among visits treated with an antibiotic, 40.4% (n = 378) received an antibiotic with MSSA coverage, while 59.6% (n = 558) received an antibiotic with MRSA coverage. Region where the visit occurred was associated with the use of MSSA versus MRSA antibiotics (p = .013). Mean age of visits receiving MSSA antibiotics was significantly older than visits receiving MRSA antibiotics, 53.8 ± 1.2 vs. 50.9 ± 0.9 (p = .045).CONCLUSIONSThis study found that providers more frequently utilize antibiotics with MRSA coverage for SSTIs. Antibiotic class chosen was associated with region, with MRSA coverage antibiotics more likely to be prescribed in the South. Additionally, individuals receiving antibiotics with MSSA coverage were older than those receiving antibiotics with MRSA coverage.

01 Dec 2017·Microbial Cell FactoriesQ2 · ENGINEERING & TECHNOLOGY

Optimization of the biotechnological production of a novel class of anti-MRSA antibiotics from Chitinophaga sancti

Q2 · ENGINEERING & TECHNOLOGY

ArticleOA

Author: Beckmann, Amelie ; Schmitt, Viktoria ; Hüttel, Stephan ; Müller, Rolf ; Stadler, Marc

BACKGROUNDRecently, the discovery of the elansolids, a group of macrolides, was reported. The molecules show activity against methicillin-resistant Staphylococcus aureus as well as other gram-positive organisms. This fact renders those substances a promising starting point for future chemical development. The active atropisomers A1/A2 are formed by macrolactonization of the biosynthesis product A3 but are prone to ring opening and subsequent formation of several unwanted side products. Recently it could be shown that addition of different nucleophiles to culture extracts of Chitinophaga sancti enable the formation of new stable elansolid derivatives. Furthermore, addition of such a nucleophile directly into the culture led exclusively to formation of a single active elansolid derivative. Due to low product yields, methods for production of gram amounts of these molecules have to be established to enable further development of this promising compound class.RESULTSProduction of elansolid A2 by C. sancti was enabled using a synthetic medium with sucrose as carbon source to a final concentration of 18.9 mg L^-1. A fed-batch fermentation was ensued that resulted in an elansolid A2 concentration of 55.3 mg L^-1. When using glucose as carbon source in a fed-batch fermentation only 34.4 mg L^-1 elansolid A2 but 223.1 mg L^-1 elansolid C1 were produced. This finding was not unexpected since elansolids A1/A2 and A3 have been reported to easily react with nucleophiles like anthranilic acid, a precursor of tryptophan biosynthesis. Due to the fact that nucleophiles can be incorporated in vivo, a fed-batch cultivation under identical conditions, with addition of anthranilic acid was carried out and lead to almost exclusive formation of elansolid C1 (257.5 mg L^-1).CONCLUSIONReproducible elansolid A2 and C1 production is feasible in different synthetic media at relatively high concentrations that will allow further investigation and semi-synthetic optimization. The feeding of anthranilic acid enables the exclusive production of the stable elansolid derivative C1, which reduces product loss by unspecific reactions and eases downstream processing. This derivative shows activity in the same range as the elansolids A1/A2. Hence, the method can possibly serve as a model-process for incorporation of other nucleophiles and biotechnological production of specifically designed molecules.

100 Deals associated with MRSA Antibiotics(Inimmune)

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Indication	Highest Phase	Country/Location	Organization	Date
MRSA - Methicillin resistant Staphylococcus aureus infection	Preclinical	United States	Inimmune Corp.	29 Oct 2024

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