The applied side of antimicrobial peptide-inducible promoters from Firmicutes bacteria: expression systems and whole-cell biosensors.
The cell envelope is an essential bacterial structure that consists of the cytoplasmic membrane, the cell wall, and-in Gram-negative bacteria-the outer membrane. Because of its crucial functions, it represents a prime antibiotic target. Monitoring and maintaining its integrity are therefore keys to survival, especially in competitive environments where antibiotics represent one means of suppressing the growth of competitors. Resistance against external antibiotic threat, as well as auto-immunity against self-produced antibiotics, is often mediated by two-component systems (2CSs). They respond to antibiotic threat by inducing gene expression that results in the production of specific resistance determinants. The underlying transcriptional control is exhibited at the level of specific target promoters, which usually share a number of relevant features: They are tightly controlled and only induced in the presence of specific (sets of) antibiotics. This induction is dose dependent and often very sensitive, that is, it occurs well below inhibitory antibiotic concentrations. Because of these characteristics, a number of well-characterized cell envelope stress-inducible promoters have been developed for two different applied purposes: first, as whole-cell biosensors for antibiotic detection and mechanism-of-action studies, and second, as antibiotic-inducible expression systems for biotechnological purposes. The current state of research in both fields will be discussed in this review, focusing on 2CS-regulated promoters from Firmicutes bacteria that are induced to mediate resistance against antimicrobial peptides (AMPs) targeting the cell envelope.
Institute of Microbiology, Technische Universität (TU) Dresden, 01062, Dresden, Germany.
Diana
D
Wolf
Institute of Microbiology, Technische Universität (TU) Dresden, 01062, Dresden, Germany. Thorsten.Mascher@tu-dresden.de.
Thorsten
T
Mascher
D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000494:pharmacology*; D001412:Bacillus subtilis / Q000187:drug effects / Q000235:genetics*; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D015374:Biosensing Techniques; D002462:Cell Membrane / Q000187:drug effects; D002473:Cell Wall / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial; D017930:Genes, Reporter; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000235:genetics; D013294:Lactococcus lactis / Q000187:drug effects / Q000235:genetics*; D011401:Promoter Regions, Genetic
D023181:Antimicrobial Cationic Peptides; D001426:Bacterial Proteins
Cell wall antibiotic; Expression system; Inducible promoter; Signal transduction; Two-component system; Whole-cell biosensor