15 November 2012

Histones against bacteria

A new type of body reaction to bacterial infection has been discovered

NanoNewsNet based on materials from the University of California – Irvine: New type of bacterial protection found within cellsBiologists from the University of California at Irvine have found that histone proteins, whose main function is the packaging of DNA in the nucleus of the cell, are able to suppress the vital activity of intracellular bacteria.

This powerful antibacterial activity represents a previously unknown type of reaction of the body to intracellular pathogens.

A new role of histone proteins in fruit flies was discovered by an expert in the field of developmental biology and cell biology, Professor Steven Gross and his colleagues. Scientists believe that their discovery may portend a completely new approach to combating intracellular bacterial growth.

A large number of histones are present in most cells of animal organisms, and the main task of these proteins is to assist DNA in folding into compact functional structures inside the nucleus. According to Professor Gross, scientists already have evidence that histones located outside cells can protect the body from extracellular bacteria. However, many bacteria penetrate into cells, where they can multiply freely without fear of attacks from the body's immune system.

In principle, Professor Gross says, being inside cells, histones can protect them from such bacteria, but for many years such a scenario was considered unlikely because most histones are bound to DNA in the cell nucleus, while bacteria multiply in the cell fluid – the cytosol – that is, outside the nucleus. Moreover, free histones can be extremely dangerous for cells, which is why most species have evolved mechanisms for detecting and destroying free histones in the cytosol.

In their study, Professor Gross and his colleagues showed that histones associated with lipid (fat) droplets can protect cells from bacteria without causing any harm to the cells. In experiments on fruit fly embryos, drosophila scientists have proved that lipid-bound histones can be released and kill bacteria.

The researchers injected the same amount of bacteria into wild-type fruit fly embryos, which form lipid-bound histones, and into genetically modified embryos that do not have such histones. Histone-deficient embryos were 14 times more likely to die from bacterial infections. Similar results were obtained in experiments on adult flies. In addition, there is evidence that histones can protect against bacteria and mice.

Approximately equal amounts of E. coli bacteria (strain YD133) labeled with green fluorescent protein were introduced into wild-type (WT) and mutant embryos (Jabba f07560) of fruit flies of fruit flies. The bacteria grew only in mutant embryos that lack histones associated with fat droplets. Bacterial growth inside the embryos was evaluated 2, 24 and 48 hours after administration (ncbi.nlm.nih.gov ).

The Jabba protein and its role in the retention of histones in intracellular lipid accumulations were first described recently in an article by Li et al. Lipid Droplets Control the Maternal Histone Supply of Drosophila Embryos (Current Biology, October 18, 2012) – VM.

"We have established that these histone proteins have the widest antibacterial spectrum," says Professor Gross. "If we can learn how to control this system to increase histone levels, one day we will have a new way to treat patients with severe bacterial infections. Since histones on lipid droplets are currently found in different cells – human, mice and flies – it is likely that this system can be universal."

The details of the study can be found in the article A novel role for lipid droplets in the organizational antibacterial response, published in eLife, a new peer–reviewed open access journal published with the support of the Howard Hughes Medical Institute, the Max Planck Society and the Wellcome Trust.

Portal "Eternal youth" http://vechnayamolodost.ru15.11.2012

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