DNA in Human Genomes

A new study finds strong evidence that bacteria can transfer genes into human genomes, especially in cancer cells. By Ed Yong | June 20, 2013 | The Scientist A team of scientists from the University of Maryland School of Medicine has found the strongest evidence yet that bacteria occasionally transfer their genes into human genomes, finding bacterial DNA sequences in about a third of healthy human genomes and in a far greater percentage of cancer cells. The results, published today (20 June) in PLOS Computational Biology, suggest that gene transfer from bacteria to humans is not only possible, but also somehow linked to over-proliferation: either cancer cells are prone to these intrusions or the incoming bacterial genes help to kick-start the transformation from healthy cells into cancerous ones. “It really does seem that human genome sequence data from somatic cells show signs of LGT events from bacteria, and so do cancer cells,” said Jonathan Eisen from University of California, Davis, who coordinated the peer review of the new study but was not involved in the work. “Wild stuff does happen.” The trillions of bacteria in our bodies regularly exchange DNA with each other, but the idea that their genes could end up in human DNA has been very controversial. In 2001, the team that sequenced the first human genome claimed to have found 113 cases of such lateral gene transfers (LGT), but their conclusion was later refuted. This high-profile error “had a chilling effect on the field,” according to Julie Dunning Hotopp who led the new study. Although her team has since found several cases of LGT between bacteria and invertebrates, “it’s still difficult to convince people that it may be happening in the human genome,” she said. Rather than looking for bacterial genes that had become permanent parts of the human genome, Dunning Hotopp’s team searched for traces of microbial DNA in somatic cells—the cells of the body that do not form gametes. Lab members David Riley and Karsten Sieber scanned publicly available data from the 1000 Genomes Project and found more than 7,000 instances of LGT from bacteria, affecting around a third of the people they studied. When they analyzed sequences from the Cancer Genome Atlas, they discovered 691,000 more instances of LGT 99.9 percent of these came from tumor samples rather than normal tissues. Acute myeloid leukaemia cells were particularly rife with bacterial sequences. A third of the microbial genes came from a genus called Acinetobacter, and had been inserted into the mitochondrial genome. Stomach cancer cells also contained lots of bacterial DNA, especially from Pseudomonas. Most of this DNA had been inserted into five genes, four of which were already known to be proto-oncogenes that can give rise to cancer, emphasizing a possible link between LGT and cancerous growth. “Finding these integrations in multiple individuals, as well as in the proto-oncogenes, really spoke to how significant this might be,” said Dunning Hotopp. “We know already that a significant proportion of cancers are due to insertion of genetic material from viruses,” said Etienne Danchin from the French National Institute for Agricultural Research, who reviewed the paper. “But this is the first time, as far as I know, that HGT from bacteria could be suspected as a cause of cancer.” However, Dunning Hotopp is very clear that her results tell us nothing about whether the inserted bacterial DNA contributed to causing the cancers, or were just along for the ride. To get at the question of causation, researchers could deliberately add bacterial DNA into the same sites within human cell lines to see if they turn cancerous, she said. But even if the bacterial LGT can initiate over-proliferation, it would be hard to prevent such transfers with antibiotics. “You don’t know when these transfers occur, and you can’t give people antibiotics their entire life,” said Dunning Hotopp. “A vaccine would be nice, but that is assuming these are causative.” “LGT is incredibly important in evolution but many claims of specific cases of LGT have been seriously flawed,” said Eisen. “I came into this as a serious skeptic. It just seemed so improbable.” But the team won him over. They ran an extensive set of checks to make sure that these bacterial sequences were not laboratory artifacts and had not come from contaminating microbes. For example, they showed that LGT was more common in cancer cells than healthy tissue, and two out of ten cancer types were particularly hard hit. If the bacterial integrations were artifacts of the methodology, it should be equally common in any tissue sample. The team also focused on sequences with high coverage—that is, those which had been read many times over. When the team found evidence of LGT, it was consistent across all of these reads. “In the end, the authors addressed every single question that I and the reviewers raised,” said Eisen. Hank Seifert from Northwestern University, who was not involved in the study, remains cautious. “This paper is very interesting and potentially important,” he said. “However, until the direct analysis of specific tumor cells can be performed to validate that these are real events, this work [is] still speculative.” But Dunning Hotopp’s team cannot do these validation studies herself. For privacy reasons, they cannot access the original tumor samples that their data came from. “People with access to the samples need to validate that the integrations are correct,” she said.  Danchin agrees that the results need to be validated but said, “I am personally convinced what they have found by screening the different databases is true. I think LGT happens much more frequently than we imagine but, most of the time, is just not detectable.” D. R. Riley et al., “Bacteria-human somatic cell lateral gene transfer is enriched in cancer samples,” PLOS Computational Biology, tbc, 2013.

Key host–pathogen interactions for designing novel interventions against Helicobacter pylori

Helicobacter pylori is a Gram-negative bacterium which has exquisitely adapted to survive in the acidic, hostile environment of the stomach. H. pylori is extremely motile and is found in the mucus layer lining the stomach. By penetrating this thick mucus layer, the bacteria can attach to gastric epithelial cells, thus avoiding being ‘washed’ through the stomach. H. pylori infection tends to persist for the life of the host and, with more than half the population of the world being infected, it is not surprising that H. pylori strains have co-evolved with Homo sapiens. For this reason, and due to several cunning adaptations, the bacteria are able to induce low-level inflammation to gain access to the nutrients required for them to grow and survive, but simultaneously evade host immune responses. Importantly, H. pylori is presently the only bacterial species classified as a type 1 carcinogen by the World Health Organization (WHO) and remains a significant cause of morbidity and mortality worldwide. Approximately one in five infected individuals develop disease, including either peptic ulcer disease, gastric mucosal-associated lymphoid tissue lymphoma and, in the worst case (approximately 1–2% of infected individuals), gastric adenocarcinoma. Gastric cancer remains the second leading cause of death from malignancy worldwide and, with H. pylori being a major cause, it is clear that H. pylori infection still has a major impact on the global disease burden. Clearly there is a need to develop novel therapies and, ideally, a highly efficacious vaccine, based on a sound understanding of H. pylori and its interplay with the human host. This review will summarize recent findings in the context of host–pathogen interactions and modulation of inflammation as well as highlighting recent advances in vaccine development.

Every, A.L (2013) Key host–pathogen interactions for designing novel interventions against Helicobacter pylori Trends in Microbiology, 21, 253–259.

Don't touch?

Next time you enter a new hotel room, you might think twice before touching the light switch or reaching for the remote. Those are two of the top surfaces most likely to be contaminated with bacteria, according to a study aimed at boosting hotel cleaning practices.

For more see: http://vitals.msnbc.msn.com/_news/2012/06/17/12241651-germiest-hot-spots-in-hotels-tv-remote-light-switch-study-finds?chromedomain=testblog

Your Computer Mouse Carries More Germs Than A Toilet Seat

The average computer mouse is three times dirtier than a toilet seat, according to an alarming new study.
Researchers blame the results on  workers who eat at their desks, turning work stations into breeding grounds for harmful bugs and germs. And men are far more filthy than their female counterparts - with 40 per cent more bacteria lurking in male mice.Keyboards were the second most grubby item in the office, ahead of phones and chairs.Initial Washroom Hygiene, which carried out the tests, said computer mice also carried twice as many bugs as a toilet flush handle.
Researchers swabbed 158 items seized from 40 desks at three office locations and compared the results with data on toilet hygiene, including 28 loo seats, obtained from other buildings. Four-in-10 desks were home to at least one item with very high levels of bacteria and surface contamination which posed a risk to health.
Initial Technical manager Peter Barratt said: 'It is now common for office workers to spend their lunch hour eating at their desk - often surfing the web or continuing to type at the same time.
'This leaves crumbs and other food residue all over the work station, particularly on mice and keyboards, making them ideal places for bacteria and other microorganisms to survive and multiply.
'In addition because they are electrical devices these items aren’t cleaned as regularly or as thoroughly as other parts of the office, or even as the desks themselves.'
The mouse isn't the only everyday item found to be filthier than the average toilet seat - research has discovered more bacteria on kitchen work surfaces, steering wheels, restaurant high chairs, shopping trolleys and even lift buttons.
–Daily Mail, London

Antibiotic resistance: we must act now says WHO.

http://www.nhs.uk/news/2012/03march/Pages/antibiotic-resistance-who-strategy.aspx

Staphylococcus aureus might be an intracellular pathogen

Increasing evidence indicates that Staphylococcus aureus might be a facultative intracellular pathogen. In particular, certain subpopulations, called small colony variants (SCVs), seem to be well adapted to the intracellular milieu. When compared to ‘normal’ staphylococcal strains, SCVs show increased uptake by host cells, resistance to intracellular defences and reduced stimulation of host defences. We propose that the ability to form two subpopulations with different phenotypes might allow S. aureus the option for both extra- cellular and intra-cellular survival in the host.
Trends in Microbiology 2012 (Article in Press)

http://images.cell.com/images/Edimages/chom/TIM_Feb.pdf

Gene could be factor in frequent cold sores

People who get frequent flare-ups of cold sores may have variations of an obscure gene, according to a study published this week in the Journal of Infectious Diseases. This is the first gene to be associated with cold sore outbreaks.
Cold sores are the lesions caused by herpes simplex virus type 1, a persistent and common virus. The sores usually appear on the lip, around the mouth and sometimes on the nose, chin and fingers. Apart from the distress the sores can cause by their appearance, they can be painful and stick around for two weeks.
The sores also are infectious. Once a person has the virus, there’s no cure or way to predict or prevent the cold sores. The virus remains in the body and then unpredictably flares up in an outbreak of sores.  There are medications to relieve the symptoms.
Herpes simplex virus type 1 is different from genital herpes, which is herpes simplex virus type 2.
When will we see a herpes cure?
Researchers from University of Utah and the University of Massachusetts say the gene behind the frequent cold sores is C21orf91. Everyone has the gene, but there are two variations of the C21orf91 that are associated with the greater frequency of the outbreaks.
This doesn’t mean that people who have one of these two gene variations will automatically get a slew of cold sores.
“Twenty-one percent of the trait is due to genetic factors,” said study author, Dr. John Kriesel who is also a research associate professor of infectious diseases at the University of Utah School of Medicine. This means that 79% is due to other factors such as the virus strain and environmental factors.
Kriesel and the co-authors reached their findings after analysing data from the gene sequences from 618 study participants - half of whom had cold sore outbreaks.
“The hope is if we can figure out what this protein is doing, we’ll find insight,” Kriesel said.  “There are other forms of herpes that are much more serious than cold sores.”
Post by: Madison Park - CNNhealth.com Writer/Producer