Many bacteria secrete hydrogen peroxide (H 2 O 2 ) in order to inhibit other competing microbes and suppress host immunity. The secreted H 2 O 2 does great harm to the host. However, no strategy has been found to effectively eliminate the H 2 O 2 -secreting bacteria.
The research team led by LV Weifu, WANG Yucai from the First Affiliated Hospital of University of Science and Technology of China (USTC) of the Chinese Academy of Sciences developed Fe 3+ -doped metal organic frameworks loaded with antibiotic ampicillin (nFMs@Amp) which effectively treated H 2 O 2 -secreting bacteria, alleviating pulmonary injury and preventing systemic sepsis. The study was published in Biomaterials .
Researchers first confirmed that H 2 O 2 secreted by S. pneumoniae strain-1 ( Sp 1) could do great harm to DNA, and Sp 1 can make “breaches” on the host's alveolar-capillary barrier, through which the bacteria further invade into the blood circulation.
In order to learn in detail how the nFMs@Amp worked, researchers conducted a series of characterizations and revealed that the doped Fe 3+ first catalyzed the degradation of H 2 O 2 in a fenton/fenton-like manner, which led to the collapse of nFMs@Amp. The loaded antibiotic Amp was thus released, and specifically killed drug-sensitive bacteria. Drug-resistant bacteria can also be eliminated, thanks to the strong oxidant ·OH generated in H 2 O 2 degradation. Considering that the active ·OH has the potential to damage host tissue and cells, they checked the levels of ALT and AST in the mouse serum and found no significant change, which indicated good biocompatibility of nFMs@Amp.
The following in vitro and in vivo experiment both proved that nFMs@Amp could provide a lasting protection against H 2 O 2 -induced DNA damage. More comprehensive experiments were conducted on Sp 1 infected mice to test the actual effect of nFMs@Amp. The researchers discovered less tissue damage and weight loss of Sp 1 infected mice after being treated with nFMs@Amp. Most mice treated with nFMs@Amp survived infection with a lethal dose of Sp 1. The evidence demonstrated the effect of nFMs@Amp on alleviation of pulmonary injury and prevention of systemic sepsis.
In conclusion, nFMs@Amp can serve as a potential treatment to H 2 O 2 -secreting bacteria, providing both protection against DNA damage and antibacterial therapy. This work created a new path for the treatment of toxin-secreting bacteria.
Biomaterials
10.1016/j.biomaterials.2021.121237
Nano-metal–organic-frameworks for treating H2O2-Secreting bacteria alleviate pulmonary injury and prevent systemic sepsis
1-Nov-2021