Researchers Discover the Mechanisms That Lead to Bacterial Pathogenicity

Scientists have discovered the mechanisms that lead to pathogenicity in bacteria. Proteins similar to eukaryotic histones pack and coil the DNA strand. This process triggers the activation of genes that control pathogenicity. The details are in a study just published in the journal Science Advances.

In order to become pathogenic, the bacterial DNA must first be organized and condensed. In eukaryotes, including humans, proteins called histones drive this process. The DNA wraps around the histones and condenses inside the nucleus. Prokaryotes, such as bacteria, lack histone proteins. They instead use HU proteins. HU proteins act in a similar way to histones; the DNA wraps around them and the chromosomes are then condensed in the nucleoid. Previous research had shown that this process seemed to trigger pathogenicity but the actual mechanisms were unknown.

Researchers from the Department of Energy’s Lawrence Berkeley National Laboratory used a special beamline to get images of HU proteins working at different resolutions. The Structurally Integrated Biology for Life Sciences beamline, or SIBYLS, uses both X-ray crystallography and SAXS technology. SAXS stands for small angle X-ray scattering and helped the researchers get images of the HU proteins in action. X-ray crystallography allowed them to get detailed data on how the HU proteins interacted with the bacterial DNA. The researchers also teamed up with the director of the National Center for X-ray Tomography to get even more data.

The team found that the HU proteins helped package and condense bacterial DNA strands. If the DNA strand became supercoiled, this triggered the expression of certain genes. These genes, after being switched on, started a cascade of events leading to pathogenicity. The process was very fast, allowing bacteria to rapidly adapt to new situation and environments.

These findings are helping scientists understand how a bacterium can switch to a pathogenic state. If we can understand exactly how this happens, we may be able to reverse or prevent pathogenicity. One possibility would be developing drugs that target HU proteins. The authors believe that this could lead to better treatments for bacterial infections.

REFERENCE

Michal Hammel  et al. HU multimerization shift controls nucleoid compaction. Science Advances (2016).

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