New Type Of Bacterial Protection Found Within Cells

Source : University of California - Irvine

UCI study reveals novel immune system response to infections

— Irvine, Calif., November 13, 2012 —

UC Irvine biologists have discovered that fats within cells store a class of proteins with potent antibacterial activity, revealing a previously unknown type of immune system response that targets and kills bacterial infections.

Steven Gross, UCI professor of developmental & cell biology, and colleagues identified this novel intercellular role of histone proteins in fruit flies, and it could herald a new approach to fighting bacterial growth within cells. The study appears today in eLife, a new peer-reviewed, open-access journal supported by the Howard Hughes Medical Institute, the Max Planck Society and the Wellcome Trust.

“We found that these histone proteins have pan-antibacterial abilities and can have a wide-ranging effect,” Gross said. “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.”

Histones exist in large numbers in most animal cells; their primary job is to help DNA strands fold into compact and robust structures inside the nucleus. Gross said 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.

In principle, Gross said, 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.

In their study, Gross and colleagues demonstrate 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.

The researchers 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,” Gross said.

Preetha Anand, Silvia Cermelli, Robilyn Sigua and Lan Huang of UCI; Zhihuan Li and Michael Welte of New York’s University of Rochester; Adam Kassan, Marta Bosch and Albert Pol of the August Pi i Sunyer Biomedical Research Institute in Barcelona, Spain; and Andre Ouellette of USC contributed to the study (Anand et al. eLife 2012;1:e00003. DOI: 10.7554/eLife.00003), which was supported by the National Institutes of Health (grants GM64624 and GM64687), the National Science Foundation and the Spanish Ministry of Science & Innovation.

About the University of California, Irvine: Founded in 1965, UCI is a top-ranked university dedicated to research, scholarship and community service. Led by Chancellor Michael Drake since 2005, UCI is among the most dynamic campuses in the University of California system, with more than 28,000 undergraduate and graduate students, 1,100 faculty and 9,400 staff. Orange County’s second-largest employer, UCI contributes an annual economic impact of $4.3 billion. For more UCI news, visit www.today.uci.edu.

News Radio: UCI maintains on campus an ISDN line for conducting interviews with its faculty and experts. Use of this line is available for a fee to radio news programs/stations that wish to interview UCI faculty and experts. Use of the ISDN line is subject to availability and approval by the university.

  • <<
  • >>

Articles List

  • What Doesn’t Kill You … Testing for Chemical Toxicity

    What Doesn’t Kill You … Testing for Chemical Toxicity

    Understanding the effects of small molecules, compounds and chemicals on cells is the very core of drug discovery, one in which the pharmaceutical industry continues to invest billions of dollars. Yet alongside the question of whether such entities have a desired effect looms that of whether they have a toxic effect on those cells—and ultimately the tissues and organisms the cells compose. This question has equal importance to those who protect our environment and assure that our food is safe to eat. Testing chemical toxicity can take many forms, from looking for simple surrogates of death, such as the inability to exclude trypan blue, to sophisticated measures of changes in a specific cell type’s physiology. Various assays look at pathways leading to cell death, membrane integrity, depletion of energy, ability to proliferate and changes in differentiation. They are accomplished using instruments ranging from a hemocytometer and light microscope; to a Coulter counter, microplate reader or flow cytometer; to a high-content analysis solution found principally in screening cores at biotech and larger pharmaceutical companies. Screens for loss of viability are often the first line of inquiry, and only after an entity is shown to cause a decrease in survival is it then subjected to more nuanced assays [1]. Here we look at the principal means by which entities are tested for their effects on viability.
  • Data Mining for Cancer Genes

    Data Mining for Cancer Genes

    Next-generation sequencing (NGS), combined with other molecular characterization technologies, has captured a wealth of sequence data from both normal and diseased human

Disqus Comments