Many bacteria secrete hydrogen peroxide (H2O2) in order to inhibit other competing microbes and suppress host immunity. The secreted H2O2 does great harm to the host. However, no strategy has been found to effectively eliminate the H2O2-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 Fe3+-doped metal organic frameworks loaded with antibiotic ampicillin (nFMs@Amp) which effectively treated H2O2-secreting bacteria, alleviating pulmonary injury and preventing systemic sepsis. The study was published in Biomaterials. Researchers first confirmed that H2O2 secreted by S. pneumoniae strain-1 (Sp1) could do great harm to DNA, and Sp1 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 Fe3+ first catalyzed the degradation of H2O2 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 H2O2 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 H2O2-induced DNA damage. More comprehensive experiments were conducted on Sp1 infected mice to test the actual effect of nFMs@Amp. The researchers discovered less tissue damage and weight loss of Sp1 infected mice after being treated with nFMs@Amp. Most mice treated with nFMs@Amp survived infection with a lethal dose of Sp1. 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 H2O2-secreting bacteria, providing both protection against DNA damage and antibacterial therapy. This work created a new path for the treatment of toxin-secreting bacteria.
