"Where are the Aliens or how did we got stuck HERE?" a.k.a. "Gene therapy and its connection to

DiRuggiero's team has learned that when it comes to DNA repair, Halobacterium is something of a "Renaissance bug."
It dabbles in a bit of everything. Its genome of only 2,400 genes contains several distinct sets of DNA-repair
mechanisms. Some of these sets of tools are like the DNA-repair tools found in plants and animals, other sets are
more like those of bacteria, and still others are characteristic of a lesser-known group of life called "Archaea" (the
group that Halobacterium belongs to). Halobacterium has them all. Beyond even that, Halobacterium has a few novel
DNA-repair mechanisms that no one has ever seen before!

- Halobacteria can repair badly damaged DNA. "We have completely fragmented their DNA. ...And they can
reassemble their entire chromosome and put it back into working order within several hours," says Adrienne Kish, a
member of the research group studying Halobacteria at the University of Maryland. These Archaea can also survive
extreme dryness, a hard vacuum, and of course, high salt concentrations. We are not the only ones to notice that
Halobacteria could use these capabilities to survive in space.

'Superbugs' Could Benefit Humans

Scientists have long been aware that some bacteria are remarkably resistant to radiation. The most resilient of all,
Deinococcus radiodurans, grows happily while basking in gamma-ray doses of 5,000 grays, hundreds of times as high
as a common E.coli bacterium can handle. (One gray is the amount of radiation in about 5,000 chest X-rays.)

To see if that represents a natural limit of what a cell can handle, Linda C. DeVeaux of Idaho State, Shiladitya
DasSarma of the University of Maryland Biotechnology Institute in Baltimore and co-workers took cultures of an
archaeon called Halobacterium and exposed it to the 20 million-electron-volt Idaho beam four times over four months.

"We zapped the hell out of them," DeVeaux said.

The mutant microbes that survived that experiment are unfazed by doses exceeding 11,000 grays, putting them well
into first place for radiation hardiness among actively replicating organisms.

But the achievement is about more than a place in the Guinness World Records book, DasSarma said. Tests have
revealed the molecular mechanism that appears to grant the new mutants much of their hardiness -- a mechanism
that, in a weaker form, protects and repairs DNA in human cells, too.
Rick Weiss, Washington Post Staff Writer, Tuesday, September 25, 2007; A03

Archaea and Their Potential Role in Human Disease

In a study from Spain (6), a search for antibiotic resistance within the genus Halobacterium revealed that most
extreme halophiles were resistant to ß-lactams and aminoglycosides but were sensitive to many other antimicrobials,
including macrolides, chloramphenicol, novobiocin, rifampin, bacitracin, and fluoroquinolones.

Might archaea be capable of causing disease? Current data suggest that archaea are able to colonize and survive in
humans. However, no concerted efforts have been undertaken to implicate archaea in human disease. The full
spectrum of outcomes from these archaea-human interactions, whether it includes altered host physiology, tissue
damage, or clinical disease, remains a mystery. In general, pathogens are distinguished from commensals by their
reliance on a strategy for survival and replication in or transmission from a host that regularly leads to cellular, tissue,
or organismal damage. Strategies can vary enormously, but they often define a signature for a family of pathogens.
These strategies involve gaining access to the host in sufficient numbers, adhering to and colonizing a niche, evading
host defenses, and multiplying in the host (50). If some archaea behave as pathogens they probably follow this basic
scheme, but they may use fundamentally different mechanisms at some or all of these steps.

(i) Access and colonization. The ubiquity of archaea in nature provides them ample opportunity for access to and
colonization of susceptible hosts. In fact, we know of multiple niches for archaea in the human host. Methanogens, for
example, have been identified among the human colonic (36), subgingival (1, 6, 29), and vaginal flora (2). Given their
requirement for strictly anaerobic microenvironments, methanogens are likely to exist in human anatomic sites where
well-characterized anaerobic bacteria flourish, possibly as coinhabitants.

Methanogens are the only archaea that have been identified in humans, despite human contact with other archaeal
types, such as extreme halophiles (commonly found on such high-salt foods as sausages, salt pork, and fish (26).
Methanogens were also once thought to be the exclusive archaeal component in the rumen, until
Thermoplasma-associated sequences were discovered in this ecosystem using 16S rRNA sequence-based
approaches (54). The failure to identify nonmethanogens in humans may be in large part due to the lack of any
concerted efforts to define the abundance or diversity of archaea in human microenvironments. One might expect that
if methanogens were found in diseased human tissue, they would coexist with common anaerobic bacterial species at
the same site. Methanogens may follow virulence strategies in humans similar to those of the known anaerobic
bacteria. Anaerobic infectious diseases are common in humans, especially at or near sites of colonization by the
endogenous microflora, and they are usually associated with malignancy, gastrointestinal or genitourinary surgery,
bite wounds, and aspiration (14). Such diseases are often polymicrobial, with routine cultivation techniques revealing
the presence of multiple, endogenous anaerobic and aerobic bacteria. Anaerobes usually act as opportunists and
require a breakdown in a normal anatomic barrier or delivery to a privileged anatomical site (e.g., surgery or trauma),
as well as the concomitant presence of aerobes. Given their colonization of the alimentary tract in most humans, one
might implicate methanogens in the causation of known anaerobic microbial processes usually attributed to members
of the oral and gastrointestinal endogenous flora, e.g., brain, liver, and intra-abdominal abscesses, periodontal
disease, and aspiration pneumonia.

No clear association between archaea and human disease has been described to date, in part due to limitations in
our ability to detect, identify, and isolate these microorganisms. If archaea are involved in human disease, it is likely
that such involvement will be elucidated using molecular methods, given the relative difficulty of their cultivation (48,
49, 58).
Infection and Immunity, February 2003, p. 591-596, Vol. 71, No. 2