Mycobacterium tuberculosis protein X as an LPS removal and bactericidal agent

While the introduction of antibiotics into the treatment of infectious diseases marked a significant breakthrough in medical history, the drawbacks of antibiotic overuse have become both a medical and social issue. The current treatment approach to Gram-negative bacteria-induced sepsis is a prime example that illustrates the shortcomings of antibiotics. Applying antibiotics in the treatment of patients suffering from sepsis results in the killedbacteria releasing large amounts of lipopolysaccharide (LPS), which in turn brings about a systemic inflammatory reaction. In addition, the emergence of multidrug-resistant bacteria limits the therapeutic treatment options available. Toll-like receptor (TLR) 4 antagonist eritoran (E5564) and resatorvid (TAK-242) that competitively inhibits LPS, or LPS chelators such as Polymyxin B and LL-37 synthetic peptides have been tested to address these complications. However, they have proved to be clinically unviable due to their toxicity and cross reaction. Here we show that protein X extracted from Mycobacterium tuberculosis can be a promising therapeutic regimen for the treatment of the severe sepsis induced by Gram negative bacteria as not only does it exhibits an anti-microbial effect, but also inhibits excessive inflammatory reaction triggered by the LPS released from the killed bacteria through binding with LPS. Protein X is not toxic in terms of either cells or organisms, and we have verified through sepsis animal models that it notably ameliorates multi-organ damage and the mortality rate in Gram-negative bacterial sepsis. Furthermore, protein X displays an anti-microbial effect against carbapenem-resistant Acinetobacter baumannii found in sepsis patients. This verified the potential of Protein X as a promising therapeutic agent for the treatment of the severe sepsis induced by Gram negative bacteria, including the socially controversial carbapenem-resistant bacteria.