Find the weak spot in bacteria’s outer ‘armor’
Invading bacteria have membrane proteins on their surface that help them avoid detection by the body’s immune system.
As such, these proteins are regarded as excellent therapeutic targets to fight infectious diseases.
For the first time, scientists have mapped the structure of one of these proteins in two species of bacteria that cause sexually transmitted infections.
Trevor Lithgow of Monash University’s School of Biomedical Sciences has focused on understanding the structure and function of the protein, known as BamA. His lab was the first to detail how BamA evolved to promote bacterial outer membrane synthesis, thereby providing a first line of defense against the immune system.
BamA is found only on Gram-negative bacteria, many of which are highly resistant to antibiotics. The bacteria targeted by this research cause gonorrhoea and chanchroid, a sexually transmitted infections common in developing nations and a risk factor for HIV.
Lithgow says the findings were the result of a long-term collaboration with Professor Susan Buchanan of the US National Institutes of Health.
“These findings are an important stage in our long-term strategy to understand the very first steps in the invasion process—where the bacteria modify their outer surface properties—we may be able to stop the infection before it becomes established,” Lithgow says.
“These results bring us closer to understanding bacteria and exploiting their weaknesses.”
In further developments using super-resolution microscopy at the Monash Micro Imaging Facility, Lithgow’s team have focused in on the outer surfaces of individual bacterial cells to watch BamA at work.
Viewing the living bacteria in such unprecedented detail has revealed how complex the bacteria are in their ability to cloak themselves from the human immune system and establish full-blown infections. However, this complexity allows various opportunities to halt the infection process.
“Bacteria use highly complicated molecular machinery in the first stages of establishing their populations in the body. If we can knock out just one of the key aspects, we can disable the entire machinery,” says Lithgow.
Researchers from the Georgia Institute of Technology and the Diamond Light Source contributed to the study, which was published in the journal Nature.
Source: Monash University