Proteomic signatures in antibiotic research

Antibiotics disturb the physiological homeostasis of bacterial cells by interfering with essential cellular functions or structures. The bacterial proteome adjusts quickly in response to antibiotic challenge. This physiological response is specifically tailored to overcome the inflicted damage and, thus, closely linked to the antibiotic target and mechanism of action. In a way, the proteome mirrors the antibiotic insult. This connection can be exploited to guide the development of novel antibiotics. By using structurally different antibiotics, which cause the same physiological disturbance, proteomic signatures diagnostic of the mechanism of action can be defined. These proteomic signatures inform about mechanism-related differential protein expression as well as about protein modifications. This review recapitulates how antibiotic proteomic signatures are established and highlights areas of antibiotic research benefiting most from proteomic signatures. Antibacterial research programs designed to structurally advance existing antibiotic classes profit from rapid in vivo mechanism of action confirmation. What is more, a comprehensive reference compendium of antibiotic proteomic signatures allows rapid mechanism of action identification of those structurally novel compounds that inhibit known targets. Finally, novel proteomic response profiles indicate unprecedented mechanisms. Here, the proteome profile provides evidence on the nature of the antibiotic-caused physiological disturbance leading to testable hypotheses on the mechanism of action.