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Eliminating Toxin-Secreting Bacteria with Metal Organic Frameworks

This novel structure can decompose hydrogen peroxide and release antibiotics, protecting against tissue damage and preventing sepsis.

Hydrogen peroxide is a toxin secreted by some bacteria (e.g. Streptococcus pneumoniae) that can damage host cells and infected tissues, and increase vascular permeability, leading to systemic bacteremia and sepsis. Yet, given the potential devastating effects it could wreak on the human body, no strategy has been found to reduce or eradicate hydrogen peroxide-secreting bacteria.

A team led by Lv Weifu and Wang Yucai from the First Affiliated Hospital of the University of Science and Technology of China of the Chinese Academy of Sciences decided to look into this problem and successfully demonstrated how using hydrogen peroxide-reactive metal-organic framework nanosystems can treat hydrogen peroxide-secreting bacteria.

Metal-organic frameworks (MOFs) have unique porous structures and large inner cavities that allow them to carry different drugs, whose release can be activated through the disassociation of linkers in response to stimuli. More importantly, doping of metal atoms in the structure provides active centres for the catalysis of many chemical reactions. Hence, MOFs make promising materials for treating hydrogen peroxide-secreting bacteria and protecting infected tissues.

In mice infected with S. pneumoniae taken from patients, pneumococcal hydrogen peroxide caused damage to host cells and breached alveolar-capillary barriers, leading to bacterial invasion into the bloodstream.

In this study, the team designed a Fe3+-doped MOFs loaded with antibiotic ampicillin (nFMs@Amp) to treat hydrogen peroxide-secreting bacteria like S. pneumoniae, thereby relieving pulmonary injury and preventing systemic sepsis.

To find out how nFMs@Amp worked, the researchers conducted a series of characterisations and revealed that the doped Fe3+– ions first facilitated the degradation of hydrogen peroxide in a Fenton/Fenton-like reaction, which led to the decomposition of nFMs@Amp and the release of ampicillin to kill drug-sensitive bacteria. Furthermore, as hydrogen peroxide is decomposed by nFMs@Amp, hydroxyl radicals produced from the decomposition can also kill drug-resistant bacteria. Considering that the active hydroxyl radicals could damage host tissue and cells, the researchers checked the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the mouse serum and observed no significant changes after 30 days, suggesting nFMs@Amp’s good biocompatibility.

Subsequent in vitro and in vivo experiments both demonstrated that nFMs@Amp could provide lasting protection against hydrogen peroxide-induced DNA damage. Further experiments to test the actual effect of nFMs@Amp were carried out with Sp1 infected mice, and the researchers observed less tissue damage and weight loss of Sp1 infected mice after being treated with nFMs@Amp. They found that nFMs@Amp killed over 98 per cent of S. pneumoniae and reported that over 90 per cent of mice infected with a lethal dose of Sp1 survived infection.

From the results, the team concluded that treatment with nFMs@Amp was very effective against deadly streptococcal diseases in mice, presenting a potential treatment for hydrogen peroxide-secreting bacterial infections and forging new path for the clinical treatment of toxin-secreting bacteria. [APBN]

Source: Wu et al. (2021). Nano-metal–organic-frameworks for treating H2O2-Secreting bacteria alleviate pulmonary injury and prevent systemic sepsis. Biomaterials, 279, 121237.