A team of biologists from Spain and the United States has discovered that fats within cells store a class of basic proteins, called histones, with potent antibacterial activity, revealing a previously unknown type of bacterial protection.
Histones are highly alkaline proteins found in large numbers in most animal cells. Their primary job is to help DNA strands fold into compact and robust structures inside the nucleus.
“We found that these histone proteins have pan-antibacterial abilities and can have a wide-ranging effect,” said Prof Steven Gross of the University of California in Irvine, senior author of the study published in the journal eLife.
“If we can discover how to manipulate the system to increase histone levels, we may one day have a new way to treat patients with bad bacterial infections.”
“There is some evidence that histones secreted from cells protect against bacteria living outside cells. However, many bacteria enter cells, where they can avoid the immune system and continue replicating,” Prof Gross said.
“In principle, histones could protect cells against such bacteria from the inside, but for many years this was thought unlikely because most histones are bound to DNA strands in the cell nucleus, whereas bacteria multiply in the cellular fluid outside the nucleus, called cytosol. Additionally, free histones can be extremely damaging to cells, so most species have developed mechanisms to detect and degrade free histones in the cytosol.”
The scientists have demonstrated that histones bound to lipid (fat) droplets can protect cells against bacteria without causing any of the harm normally associated with the presence of free histones. In experiments with lipid droplets purified from Drosophila fruit fly embryos, they show that lipid-bound histones can be released to kill bacteria.
They injected similar numbers of bacteria into Drosophila embryos that contained lipid-bound histones and into embryos genetically modified to not contain them. They discovered that the histone-deficient flies were 14 times more likely to die of bacterial infections. Similar results were found in experiments on adult flies. Additional evidence suggested that histones might also protect mice against bacteria.
“Because numerous studies have now identified histones on lipid droplets in many different cells – from humans as well as mice and flies – it seems likely that this system may be quite general,” Prof Gross concluded.
Bibliographic information: Preetha Anand et al. 2012. A novel role for lipid droplets in the organismal antibacterial response. eLife, 1: e00003; doi: 10.7554/eLife.00003