Bacteria are capable of remarkable adaptations to their environment, including undesirable bacterial resistance to antibacterial agents. One of the most serious cases is an infection caused by multidrug-resistant Staphylococcus aureus, which has unfortunately also spread outside hospitals. Therefore, the development of new effective antibacterial agents is extremely important to solve the increasing problem of bacterial resistance. The bacteriolytic enzyme autolysin E (AtlE) is a promising new drug target as it plays a key role in the degradation of peptidoglycan in the bacterial cell wall. Consequently, disruption of function can have an immense impact on bacterial growth and survival. An in silico and in vitro evaluation of iminosugar derivatives as potent inhibitors of S. aureus (AtlE) was performed. Three promising hit compounds (1, 3 and 8) were identified as AtlE binders in the micromolar range as measured by surface plasmon resonance. The most potent compound among the SPR response curve hits was 1, with a K_D of 19 μM. The K_D value for compound 8 was 88 μM, while compound 3 had a K_D value of 410 μM.

Artificial neural networks (ANNs) are nowadays applied as the most efficient methods in the majority of machine learning approaches, including data-driven modeling for assessment of the toxicity of chemicals. We developed a combined neural network methodology that can be used in the scope of new approach methodologies (NAMs) assessing chemical or drug toxicity. Here, we present QSAR models for predicting the physical and biochemical properties of molecules of three different datasets: aqueous solubility, acute fish toxicity toward fat head minnow, and bio-concentration factors. A novel neural network modeling method is developed by combining two neural network algorithms, namely, the counter-propagation modeling strategy (CP-ANN) with the back-propagation-of-errors algorithm (BPE-ANN). The advantage is a short training time, robustness, and good interpretability through the initial CP-ANN part, while the extension with BPE-ANN improves the precision of predictions in the range between minimal and maximal property values of the training data, regardless of the number of neurons in both neural networks, either CP-ANN or BPE-ANN.

Staphylococcus aureus is a widespread gram-positive pathogen in humans and animals. Autolysin E (AtlE) is an enzyme from S. aureus which belongs to the glycoside hydrolase 73 family.