The development of novel drugs against Gram-negative bacteria represents an urgent medical need. To overcome their outer cell membrane, we synthesized conjugates of antibiotics and artificial siderophores based on the MECAM core, which are imported by bacterial iron uptake systems. Structures, spin states, and iron binding properties were predicted <i>in silico</i> using density functional theory. The capability of MECAM to function as an effective artificial siderophore in <i>Escherichia coli</i> was proven in microbiological growth recovery and bioanalytical assays. Following a linker optimization focused on transport efficiency, five β-lactam and one daptomycin conjugates were prepared. The most potent conjugate <b>27</b> showed growth inhibition of Gram-positive and Gram-negative multidrug-resistant pathogens at nanomolar concentrations. The uptake pathway of MECAMs was deciphered by knockout mutants and highlighted the relevance of FepA, CirA, and Fiu. Resistance against <b>27</b> was mediated by a mutation in the gene encoding ExbB, which is involved in siderophore transport.