A study in the journal “Cell Research” shows that blood clotting factors can play a role in anti-infective mechanisms. The basic role of these factors is to form a clot after an injury. But these factors can also help to fight the resistant bacteria in the body.
The outer membrane of gram-negative bacteria makes them resistant to antibiotic drugs
Bacteria can pose a major health risk because of an increase in the resistance to present antibacterial drugs. Gram-negative bacteria are difficult to kill than gram-positive bacteria. It may be due to the presence of outer membrane in the former ones.
The cell envelopes in gram-negative bacteria consist of an inner cell membrane, a cell wall (thin) and an outer membrane. The outer membrane may decrease a cell’s permeability and result in resistance to antibiotics.
Recently, the WHO has given a list of 12 bacteria that are fatal for human health due to this resistance. Hemophilia is a disorder in which one of the blood clotting factors is missing. A person with this disorder bleeds for a long time due to the lack of clot formation.
The research team has found that deficiency of these factors can lead to infectious diseases. Also, the presence of diseases like sepsis and pneumonia suggests that clotting factors have a role in the anti-infective mechanisms of the body.
The blood clotting factors include factor VII, IX, and X. These may fight against gram-negative bacteria. That is resistant to drugs and may include A. baumannii and Pseudomonas. Both of these bacteria are present in the list of WHO.
In this study, the research team has stated that a class of proteins in the human can act against these bacteria. So, these proteins can help in the battle with resistant bacteria. Most of the agents with antimicrobial activity target the cell metabolism or cytoplasmic membrane of a bacterial cell.
But the blood clotting factors act differently. They break the lipopolysaccharides (LPS) in the outer membrane of bacteria. In gram-negative bacteria, LPS is vital for survival. A process known as hydrolysis can lead to the breakdown of LPS.
Blood clotting factors can hydrolyze the lipopolysaccharides present in the outer membrane of resistant bacteria
The capacity of the clotting factors to break the crucial LPS in the cell envelope implies that these factors are effective against gram-negative bacteria. Further study has shown that the clotting factors act on these bacteria by the light chain – one of the two domains in proteins.
The other domain – heavy chains do not affect this action. The lab tests have shown that treating E. coli bacteria with light chains has led to clear damage in the bacterial cell envelope. And within four hours there was full destruction of the cell envelope.
The research team has found the light chains of clotting factor VII as efficient against all the tested bacterial cells. In mice, the light chains and the whole clotting factors have helped to protect from P. aeruginosa and A. baumannii.
Currently, the studies have found no antibacterial agent that works by breaking the LPS in the outer membrane of bacteria. But the blood clotting factors play a role in anti-infective mechanisms in this way. This finding can offer new and low-cost ways to fight bacteria resistant to drugs.