Source: The First Affiliated Hospital
Written by: The First Affiliated Hospital
Edited by: Wang Dongmei
Infectious diseases are the second-leading cause of death worldwide. Gram-negative bacteria are particularly resistant to antibiotics because their cells have an impermeable lipid-based outer membrane which acts as a defensive barrier against attacks from the body’s immune system and from antibiotic drugs. But surprisingly, despite growing bacterial resistance to existing drugs, antibiotic development is steeply declining. Health experts have warned that within 20 years even routine operations such as hip replacements and organ transplants could be deadly because of the risk of infection.
But now scientists at Sun Yat-sen University led by professor Wenjian Wang and the University of East Anglia led by professor Changjiang Dong have discovered how the bug build and maintain a defensive wall — a discovery that paves the way for the development of new drugs to break through the barrier and kill the often deadly “superbugs”.
Researchers publishing a study in the journal
Nature [1] said knowing the mechanism bacteria use to keep up their defences brings scientists closer to solving the problem of antibiotic resistance, since new treatments can be designed to weaken those defences rather than attack the bacteria directly.
Their teams zeroed in on the defensive wall and found that it is built and maintained by what they described as a beta-barrel assembly machinery (BAM) containing five sub-units called BamA, BamB, BamC, BamD and BamE. They figured out how these sub-units cooperate together to fold and insert the outer membrane protein into the outer membrane, and crucially, how to disrupt that mechanism. They believe that within a few years they could develop a drug which switches off the wall-building mechanism, making the bacteria vulnerable.
This is one more very significant breakthrough since they found the mechanism of LptD–LptE complex responsible for the transport of Lipopolysaccharide (LPS) from the inner membrane to the outer membrane which also was published in the journal
Nature [2].
References (*Corresponding author)
1. Gu Y, Paterson NG, Stansfeld PJ, Zeng Y, Li H, Wang Z, Dong H, Wang W*, Dong C*. Structural basis of outer membrane protein insertion by the BAM complex.
Nature. 2016; 531:64-69.
2. Dong H, Xiang Q, Gu Y, Wang Z, Paterson NG, Stansfeld PJ, He C, Zhang Y, Wang W* & Dong C*. Structural basis for outer membrane lipopolysaccharide insertion.
Nature. 2014; 511:52-56
