TABLE 2.
Antibiotic biomarker validation based on a selection of reference agentsa
| Target area | Antibiotic | Induction of promoter:
|
||||
|---|---|---|---|---|---|---|
| yorB | yvgS | yheI | ypuA | fabHB | ||
| DNA synthesis | Moxifloxacin | + | − | − | − | − |
| Ciprofloxacin | + | − | − | − | − | |
| Trovafloxacin | + | − | − | − | − | |
| Nalidixic acid | + | − | − | − | − | |
| Novobiocin | + | − | − | − | − | |
| Pol IIIC inhibitorb | + | − | − | − | − | |
| Trimethoprim | + | − | − | − | − | |
| DNA ligase inhibitorc | + | − | − | − | − | |
| Azaserine | + | − | − | − | − | |
| Mitomycin C | + | − | − | − | − | |
| RNA synthesis | Streptovaricin | − | + | − | − | − |
| Rifampin | − | + | − | − | − | |
| Protein synthesis | Linezolid | − | − | + | − | − |
| Doxycycline | − | − | + | − | − | |
| Fusidic acid | − | − | + | − | − | |
| Chloramphenicol | − | − | + | − | − | |
| Erythromycin | − | − | −d | − | − | |
| Azithromycin | − | − | −d | − | − | |
| Gentamicin | − | − | − | − | − | |
| Kanamycin | − | − | − | − | − | |
| Puromycin | − | − | − | − | − | |
| Actinonin | − | − | − | − | − | |
| Cell wall | Cefoxitin | − | − | − | + | − |
| synthesis-cell | Oxacillin | − | − | − | + | − |
| envelope stress | Methicillin | − | − | − | + | − |
| Nisin | − | − | − | + | − | |
| Mersacidin | − | − | − | + | − | |
| Ramoplanin | − | − | − | + | − | |
| Vancomycin | − | − | − | + | − | |
| Tunicamycin | − | − | − | + | − | |
| Polymyxin B | − | − | − | + | − | |
| Fatty acid synthesis | Moiramide B | − | − | − | − | −e |
| Cerulenin | − | − | − | − | + | |
| Triclosan | − | − | − | − | + | |
| Diverse MOAs | Netropsin | − | − | − | − | − |
| Ethidium bromide | − | − | − | − | − | |
| Actinomycin D | − | − | − | − | − | |
| Monensin | − | − | − | − | − | |
| N-ethyl maleimide | − | − | − | − | − | |
+/−, reporter signal induced by at least/less than 250% (yorB), 200% (yvgS and yheI), 170% (ypuA), or 200% (fabHB) in comparison to the noninduced signal.
DNA polymerase IIIC inhibitor compound no. 1 (anilinouracil) (24).
DNA ligase inhibitor compound no. 3 (pyridochromanone) (6).
The macrolides also induce the yheI promoter as found in expression profiling experiments (11, 13). The biosensor does not respond to these antibiotics due to plasmid-encoded macrolide-lincomycin-streptogramin B resistance.
Moiramide B targets the first enzyme in fatty acid synthesis, the acetyl-coenzyme A carboxylase, which is regulated differently from the other fatty acid/phospholipid biosynthesis enzymes (13).