Teixobactina e seus análogos: uma revisão sistemática sobre os novos antimicrobianos potentes no combate ao Staphylococcus aureus Meticilina Resistente (MRSA)

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) is an agent of several serious, potentially fatal human infections that are difficult to treat due to its high resistance to many antimicrobials used in clinical practice. Therefore, teixobactin, a new antibiotic with potent action against S. aureus, discovered in 2015, is a target of analysis due to the possibility of clinical use. The present study aims to evaluate whether teixobactin and its analogues have relevant activity in combating MRSA. For this purpose, a systematic review of the literature was conducted in the PubMed, Embase, SciELO, LILACS and Web of Science databases, with the descriptors and terms: “teixobactin”, “Staphylococcus aureus”, “methicillin resistant Staphylococcus aureus” “Elephanteria terrae” and “Staphylococcaceae”. In vitro or in vivo studies with information on the antimicrobial activity, mechanism of action, cytotoxic effect or bacterial resistance of the drugs in relation to MRSA or MSSA (methicillin-sensitive S. aureus) were included. Eighteen articles were selected, in which teixobactin had a minimum inhibitory concentration (MIC) of approximately 0.25 μg/ml, due to its unique structure of 4 D-amino acids and an L-allo-endurecidin at position 10. However, due to the complex and time-consuming synthesis, there was a search for simpler compounds. The main analogues consisted of substitutions of End10 by positive charges (arginine, lysine) or neutral charges, such as leucine, with good activity, in a variable MIC range: <0.0625 to 16 μg/ml. Teixobactin and its analogues also demonstrated efficacy in combating thigh and intraperitoneal infections in mice and keratitis in rabbits. This activity is derived from the simultaneous inhibition of the synthesis of lipids II and III, precursors of peptidoglycan and teichoic acid, respectively. Bacterial resistance was detected in only one study. These drugs were safe, with low cytotoxic and hemolytic effects in the cell lines tested. Therefore, teixobactin and its analogues showed good activity in vitro and in animal models, making them a future possibility for the treatment of S. aureus infections.