Abstract: A novel amine N-halamine polymeric nanoparticles (ANHP NPs) based on 4-(allyloxy)-2,2,6,6-tetramethylpiperidine (ATMP) were well developed as an antimicrobial agents by the aid of the radical copolymerization for deactivating pathogenic bacteria. The as-prepared ANHP NPs were systematically characterized by the different physical and chemical techniques like 1H NMR, FTIR, SEM and the modified iodometric/thiosulfate method. Sterilizing action of the ANHP NPs on bacterial strain was evaluated by selecting different types of Escherichia coli (E. coli) strains as model microorganisms. The effect of DksA protein on the susceptibility of E. coli towards the ANHP NPs was investigated via the plate counting technique and the zone of inhibition test. The experimental results showed that DksA protein has an excellent resistance against the ANHP NPs. Such an in-depth study on the DksA effect on the susceptibility of E. coli against the antibiotics opens up a new thought for us to develop the novel potential antibiotics.