In summary, this study shows advantages of the CIP-R in the survival, drug resistance and virulence in iron restricted condition. DIA-based proteomics study combined with biochemical validation showed that CIP-R saves the energy by storing the glucose and increases the cell wall synthesis. Moreover, CIP-R more stable in many metabolisms than CIP-S due to the up-regulation them during long term pressure of antibiotics, which could keep the survival ability of CIP-R. These advantages not possessed by CIP-S, makes the CIP-R easier to reside in host and keep resistance ability. Importantly, CIP-R exhibited an increased virulence under iron limitation condition which is completely different from sensitive bacteria. The novel adapting countermeasures reveal the reason why the CIP-R were harder to eliminate by human immunity system and help people to find out a new method for the CIP-R treatment.