A new molecule has been found and it could help in the development of new antibiotics – a major priority for public health. Researchers reporting in Nature Microbiology describe a new protein called LoaP. This finding has given them some insight into how gene expression is controlled by proteins; while we know a lot about how the cell initiates the synthesis of a new protein, less is known about the termination of translation, and how the cell can get around sequence ‘roadblocks’ that halt synthesis.
"The upshot is that our discovery expands the basic knowledge of processive antitermination -- a type of genetic regulation -- and demonstrates that the mechanism is more widespread among bacteria than previously thought," explained Dr. Paul Straight, a Research Biochemist with Texas A&M AgriLife Research. "Antibiotic production by bacteria involves complex chemistry that is often encoded in a collection or 'cluster' of many genes. To express these giant gene clusters requires special regulation mechanisms. Understanding these mechanisms could help a great deal in the search for new antibiotics produced by bacteria." The video above illustrates antibiotic producting bacteria in action in the lab.
The investigators have not only found LoaP, or long operon associated protein, they have also learned a bit about its function. LoaP is often located adjacent to gene clusters that create antibiotics. As such, the scientists thought LoaP could offer some clues as to antibiotic production.
Straight noted that in bacteria, many genes are often strung together, and are then expressed as a whole when responding to cellular needs.
"These long chains of genes raise challenges for the molecular machines that decode DNA. Sometimes the molecular machines hit roadblocks, called terminators, and they stop and fall off the DNA. The LoaP protein is called a processive antiterminator, because it helps the machines stay on DNA and move through the roadblock terminators."
LoaP was found in the bacteria Bacillus amyloliquefaciens, which is known to repel pathogens that can attack plant roots in soil, aquaculture and hydroponic growth.
New antibiotics are becoming a major priority for people; we are faced with growing antibiotic resistance as well as emerging pathogens and must find a way to confront these threats before a serious public health crisis begins. One hurdle to new antibiotic development however, is that there is a lack of in-depth knowledge about the genetic mechanisms that underlie antibiotic synthesis. There is a huge resource of prospective new drugs in the myriad microbes that live among us; we just need to find the best way to realize their potential.
"After nearly a century of searching for bioactive natural products, bacteria still constitute a major target of modern drug discovery. The characterization of the biochemical pathways of these molecules remains a bottleneck to their development," Straight explained. “One of the key restrictions is a shortage of knowledge on the range of genetic mechanisms that can affect them. Therefore, the discovery of new classes of genetic regulatory mechanisms is likely to impact future development of natural products that counter disease."
In this work, Straight and his graduate assistant Chengxi Zhang of College Station worked in collaboration with University of Maryland researchers Jonathan R. Goodson, Steven Klupt and Dr. Wade Winkler.
If you would like to know more about gene regulation and gene clusters in bacteria, check out the following video.