Plant Natural Flavonoids Against Multidrug Resistant Pathogens.

The increasing emergence and dissemination of multidrug resistant (MDR) bacterial pathogens accelerate the desires for new antibiotics. Natural products dominate the preferred chemical scaffolds for the discovery of antibacterial agents. Here, the potential of natural flavonoids from plants against MDR bacteria, is demonstrated. Structure-activity relationship analysis shows the prenylation modulates the activity of flavonoids and obtains two compounds, α-mangostin (AMG) and isobavachalcone (IBC). AMG and IBC not only display rapid bactericidal activity against Gram-positive bacteria, but also restore the susceptibility of colistin against Gram-negative pathogens. Mechanistic studies generally show such compounds bind to the phospholipids of bacterial membrane, and result in the dissipation of proton motive force and metabolic perturbations, through distinctive modes of action. The efficacy of AMG and IBC in four models associated with infection or contamination, is demonstrated. These results suggest that natural products of plants may be a promising and underappreciated reservoir to circumvent the existing antibiotic resistance.

Discovery of Linear Low-Cationic Peptides to Target Methicillin-Resistant Staphylococcus aureus in Vivo.

The development and rapid spread of multidrug resistant (MDR) bacteria cause severe public crises. New antibacterial compounds are urgently needed to treat bacterial infections. By circumventing the disadvantages of cationic peptides here, we engineered a short, linear, low-cationic peptide bacaucin-1a, which exhibited remarkable antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). Bacaucin-1a was efficient in the prevention of MRSA associated infections in both in vitro and in vivo models with a unique mode of action. The discovery of low-cationic antibiotic candidates will extend our antibiotic pipeline in the fight against antibiotic resistant bacteria.

Nonribosomal antibacterial peptides that target multidrug-resistant bacteria.

Covering: 2000 to 2018, particularly from 2010 to early 2018 The increase in the incidence of antibiotic resistant infections is threatening to overwhelm healthcare practices worldwide. Most antibiotics in clinical use are becoming ineffective, so therefore it is imperative to develop new antibiotics and novel therapeutic strategies. Traditionally, the chemical and mechanistic diversity of nonribosomal antibacterial peptides (NRAPs) as lead compounds have meant that their structures are ideal for antibiotic discovery. Here, we summarize the state of our current knowledge about the mechanisms of antibiotic resistance, which can be used to guide the development of new antibiotics. Furthermore, we provide an overview of NRAPs for treating multi-drug resistant bacteria, including innovative approaches for screening NRAPs from new sources and the underlying mechanisms of antibacterial activity. Finally, we discuss the design of NRAP scaffolds for precise medicine and combinatorial NRAP therapies with existing antibiotics to overcome resistance, which will help to control infections in the post-antibiotic era.