Phenazines: Natural products for microbial growth control.

The unprecedented problem of antibiotic resistance has become a major challenge for public health, which has contributed to an increase in infections caused by such bacteria. These microbial infections, typically biofilm-related, are also coupled to an increase in human mortality and morbidity. However, the demand for new antimicrobial agents has increased along with the evolution of microbial resistance mechanisms. Natural products produced by bacteria, such as phenazines, have been recognized as an important source for the development of new antimicrobial agents, through the exploitation of their capacity to increase oxidative stress in other organisms. Phenazines are a large group of nitrogen-containing heterocyclic compounds and are essential for several cellular processes including iron acquisition, signaling events, enzymatic processes, and biofilm formation. Phenazine-inspired antibiotics (i.e., 2-bromo-1-hydroxyphenazine, 2,4-dibromo-1-hydroxyphenazine, bromophenazine-21, phenazine-13, and phenazine-14) are very active against a wide range of gram-positive and gram-negative bacteria, including those associated with severe infections. In this study, mechanisms of phenazine-inspired antibiotics in the cellular processes of planktonic and sessile bacteria are reviewed. Moreover, the application of phenazine-inspired antibiotics for the eradication of multidrug-resistant planktonic and biofilm bacterial infections is also reviewed.