Blood clotting factors may help fight multi-drug resistant superbugs
Coagulation factors, which are involved in blood coagulation after an injury, may offer new strategies to fight multidrug-resistant bacteria, according to a study published in Cell Research.
Infections caused by these bacteria pose an urgent risk to public health because there is a lack of effective drugs to fight them. A deficiency in blood coagulation factors - for example, in patients with blood coagulation disorder - has been associated with bacterial infections such as sepsis and pneumonia, suggesting that these coagulation factors may have a role in anti-infective mechanisms as well as blood coagulation.
Today, a group of researchers at Sichuan University in China has shown that factors VII, IX and X, well known for their role in blood coagulation, can act against Gram-negative bacteria, including highly drug-resistant pathogens such as Pseudomonas aeruginosa and Acetinobacter baumannii. These two bacteria were recently classified by the World Health Organization as one of the 12 bacteria that pose the greatest threat to human health due to their resistance to antibiotics. Gram-negative bacteria are characterized by their cellular envelopes, which consist of an inner cell membrane, a thin cell wall and an outer membrane that make them more difficult to kill.
Xu Song, the corresponding author said: In our study, we report a class of human antimicrobial proteins that are effective against certain drug-resistant "superbacteria". Unlike many antibacterial agents that target cell metabolism or the cytoplasmic membrane, these proteins act by breaking down the lipopolysaccharides of the bacterial outer membrane by hydrolysis. Lipopolysaccharides are crucial for the survival of Gram-negative bacteria."
The ability of blood coagulation factors to hydrolyze essential lipopolysaccharides in the bacterial cell envelope suggests that they could be used to fight Gram-negative bacteria. By examining the mechanism in more detail, the authors showed that coagulation factors act on bacteria through light chains - one of the two protein domains. The other domains (heavy chains) have no effect. In the laboratory, the authors showed that treatment of E. coli cells with light chains resulted in clearly observable damage to the bacterial cell envelope at the beginning and almost complete destruction of the cell in four hours.
The authors found that the light chain of coagulation factor VII was effective against all Gram-negative bacterial cells tested. Light chains, as well as coagulation factors as a whole, have also been shown to be effective in controlling Pseudomonas aruginosa and Acetinobacter baumanii infections in mice. The heavy chains had no effect.
Xu Song said: "None of the known antibacterial agents work by hydrolysis of lipopolysaccharides. The identification of the antibacterial mechanism based on lipopolysaccharide hydrolysis, combined with the antibacterial characteristics of blood coagulation factors and the ability to manufacture them on a large scale at a relatively low cost, could offer new cost-effective strategies to address the urgent public health crisis posed by drug-resistant Gram negative pathogens."
