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...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 alsocoupled to an increase in human mortality and morbidity.However,the demand for new antimicrobial agents hasincreased 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 groupof 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 veryactive 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 sessilebacteria are reviewed.Moreover,the application of phenazine-inspired antibiotics for the eradication of multidrugresistant planktonic and biofilm bacterial infections is also reviewed.展开更多
基金supported by Base Funding-LA/P/0045/2020(ALiCE),UIDB/00511/2020,and UIDP/00511/2020(LEPABE)funded by national funds through FCT/MCTES(PIDDAC)Project Germirrad-POCI-01-0247-FEDER-072237 funded by FEDER funds through COMPETE2020-ProgramaOperacional Competitividade e Internacionalização(POCI)andby national funds(PIDDAC)through FCT/MCTES.
文摘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 alsocoupled to an increase in human mortality and morbidity.However,the demand for new antimicrobial agents hasincreased 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 groupof 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 veryactive 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 sessilebacteria are reviewed.Moreover,the application of phenazine-inspired antibiotics for the eradication of multidrugresistant planktonic and biofilm bacterial infections is also reviewed.
