Mathematical analysis helps untangle bacterial chromosomes

Nov 11, 2013

When an E. coli cell divides, it must replicate its circular chromosome and pull the resulting circles apart to take up residence in two new cells. It sounds easy enough—like a magician's trick with rings—but actually involves a complicated process of unknotting and unlinking of tangled DNA.

In a new study, published online this week in the journal Proceedings of the National Academy of Sciences, SF State Associate Professor of Mathematics Mariel Vazquez and an international team of scientists offer a of how these chromosomal rings are unlinked by XerCD recombination enzymes.

Antibiotics like ciprofloxacin, prescribed for E. coli infections, target topoisomerases, another type of enzyme involved in DNA unlinking. When treated with these drugs, bacterial cells may find other modes of unlinking like the one presented in Vazquez' study, thus giving the cells a chance for survival. Understanding this unlinking process in E. coli, Vazquez noted, "could also lead to the design of better antibacterial drugs, with a clear positive effect on human health."

Infections by pathogenic E. coli and other bacteria pose a high risk to human health. According to the Centers for Disease Control and Prevention, each year in the United States at least 2 million people become infected with bacteria that are resistant to antibiotics. At least 23,000 people die each year as a direct result of these infections. In order to understand bacterial infections, it is essential to study how cells such as E. coli divide.

Biological experiments had given Vazquez and her colleagues some clues as to how the interlinked E. coli chromosomes separate prior to cell division. But the experiments could not provide a clear picture of the steps along the way to separation.

To fill in this picture, the researchers proposed a rigorous mathematical analysis that used the tangle method to model the changes that take place during the separation. In this case, the "tangle" represents two specific sites along the chromosome bound together by the recombination enzymes. They confirmed that the separation takes place in a stepwise fashion. Chromosomes interlinked after replication are converted into knots, then links again, then knots, until two free circles remain.

The researchers mention that further biological experiments can help justify the assumptions in the mathematical model, but acknowledge that those experiments would be extremely challenging to carry out. "In their absence, the mathematical analysis makes a clear-cut advance over previous biological studies," Vazquez said.

Vazquez stressed that mathematics, physics, computer science and statistics all have a role to play alongside biology in understanding DNA topology.

"It is important for people to know that DNA is not just a sequence of letters. It is a very long molecule that can adopt a complex three-dimensional structure when packaged inside a cell nucleus," she said. "Every biological process that involves DNA will be affected by its topology, and topological changes can have important biological implications."

In 2011, Vazquez was awarded a National Science Foundation CAREER grant to carry out DNA topology studies. As part of the grant, Vazquez works with local elementary schools in the San Francisco Math Circles program. In 2012, she received the Presidential Early Career Award for Scientists and Engineers (PECASE) for her work.

Explore further: Malaria transmission linked to mosquitoes' sexual biology

More information: The study "FtsK-dependent XerCD-dif recombination unlinks replication catenanes in a stepwise manner," Proceedings of the National Academy of Sciences, November 11 2013

Related Stories

How UTIs in women may damage kidneys

Nov 08, 2013

A scientist from the Institute of Translational Medicine has been awarded a £190,000 Fellowship by Kidney Research UK to investigate how the E.coli bacteria which cause Urinary Tract Infections (UTIs) move ...

Recommended for you

Malaria transmission linked to mosquitoes' sexual biology

Feb 26, 2015

Sexual biology may be the key to uncovering why Anopheles mosquitoes are unique in their ability to transmit malaria to humans, according to researchers at Harvard T. H. Chan School of Public Health and University of Per ...

Intermediary neuron acts as synaptic cloaking device

Feb 26, 2015

Neuroscientists believe that the connectome, a map of each and every connection between the millions of neurons in the brain, will provide a blueprint that will allow them to link brain anatomy to brain function. ...

Skeleton of cells controls cell multiplication

Feb 26, 2015

A research team from Instituto Gulbenkian de Ciencia (IGC; Portugal), led by Florence Janody, in collaboration with Nicolas Tapon from London Research Institute (LRI; UK), discovered that the cell's skeleton ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.