Popis: |
Enterobacter cloacae is a troublesome pathogen causing refractory infections of the lower respiratory tract, urethra and abdominal cavity, endocarditis, osteomyelitis, and neonatal septicemia. It is prone to developing resistance to ordinary antibiotics and has brought a serious problem to clinical treatment. An artful synergistic combination of an antibacterial natural product allicin and a newly isolated bacteriophage, named BD523, was constructed herein. This combination significantly lowered effective dosage of allicin and effectually overcame bacterial drug-resistance. We experimentally evidenced that allicin interacts with bacterial DNA in the groove region by inserting itself into the DNA double helix and, subsequently, disrupts the bacterial DNA by cleaving phosphate diester bonds of deoxynucleotides. Further, BD523 destroys the cell wall and membrane of bacteria by synthesizing lyase proteins, including holin and endolysins. Thus, the synergistic effect of the combination benefits from complementary targeting mechanisms of allicin and BD523. They cooperatively act on bacterial DNA, cell wall, and membrane to improve antibacterial efficiency and avoid drug-resistance. |