The Scientist :: Why group A strep targets man

The Scientist :: Why group A strep targets man

Here is a fascinating article on group A strep. Being a guy sucks sometimes.



Why group A strep targets man
Streptokinase, which activates plasminogen, may drive host specificity of bacteria | By Cathy Holding

The key to the puzzling species specificity of group A streptococci (GAS) is its production of streptokinase, which only activates the blood clot–dissolving factor plasminogen in humans, according to research published in Science this week.

The results suggest that this group of organisms, which includes the so-called flesh-eating bacterium—a highly invasive, rapidly progressing, and potentially fatal member of the GAS family that attacks soft tissues and internal organs—evades host attempts at containing infection by breaking down localized defensive blood clots and spreading through the blood stream and into surrounding tissues, according to Hongmin Sun, principal author of the study.

Bacterial streptokinase has previously been shown to interact only with the human version of plasminogen to activate its clot-dissolving function. It does not interact with plasminogen from mice or other mammals, suggesting a mechanism for specificity that the team tested by creating what they called "humanized mice" transgenic for the human plasminogen protein. When the mice were challenged with human-specific GAS, they were found to be highly susceptible to infection, said Sun, whose team was headed by David Ginsburg, professor of internal medicine and human genetics at the University of Michigan, Ann Arbor.

In addition, plasminogen-binding receptors on the surface of the GAS were critical for invasion through the skin, and the "humanized" mice were again highly susceptible to infection through this route while their normal mouse counterparts were largely unaffected. This suggests an additional mechanism by which the GAS exploit the clot-dissolving system in humans, the authors write.

Just why the same bacterium has such a range of afflictions for humans—from relatively harmless throat infections through to the potentially fatal necrotizing fasciitis—is a mystery, according to study coauthor Ulf Sjöbring, who heads a group in the Department of Laboratory Medicine at Lund University.

"We really don't know what differentiates them, they are one and the same bacteria, and we can't really say exactly why in some individuals and in some situations you get the very serious manifestations," Sjöbring told The Scientist. But the group's findings raise the possibility that polymorphic variation in the level of plasminogen, and potentially other fibrinolytic components within human populations, could represent a significant susceptibility factor for bacterial infection, he said.

However, the study does not prove that plasminogen is the primary host determinant that confers species specificity, Harry S. Courtney, associate professor in the Department of Medicine, University of Tennessee, told The Scientist by E-mail. "There are other virulence factors, such as the streptococcal pyrogenic exotoxins, that do not function well in mice [but that] may also contribute to the species specificity of group A streptococci," said Courtney, who wasn't involved in the study.

"I can only say that yes, that is certainly very true," Sjöbring told The Scientist. He said that there is an array of different putative virulence factors produced by GAS, "and if any of those is the virulence factor in, for instance, causing the flesh-eating syndrome—it's very difficult to say and it's very difficult to compare."

"The group A streptococcus in general makes its living by expressing 50 to 100 different extracellular proteins that detrimentally affect the human host," said James Musser, chief of the Laboratory of Human Bacterial Pathogenesis at the US National Institute of Allergy and Infectious Diseases, Md., who was not involved in the study.

This question of host specificity has been of interest to GAS biologists for many decades now, Musser said. "What's really new is the nice technical strategies that were used to demonstrate that concept."

"It's always excellent to be able to demonstrate that a molecule is crucial to virulence, because it adds yet another potential target for therapeutic interventions. This is a very important demonstration that streptokinase may be an important target for therapeutic maneuvers—no question," Musser said.
Links for this article
R. Lewis, "Clot busters to do laundry?" The Scientist, 15:10, January 22, 2001.
http://www.the-scientist.com/yr2001/jan/lewis_p10_010122.html

Let the Hand Wringing Begin

Quite a good game by Argentina, especially the end-of-game dunk. We'll see if the U.S. has the stomach for the kind of angst and self-criticism that we have mustered over losses in hockey. I don't know if they are up to the challenge.

Argentina Beats U.S. in semifinals - Friday August 27, 2004 3:02PM

Taekwondo? Total Bullshit.

Taekwondo is a scam foisted upon the world by greedy Koreans. Watch some of the crappy action, then read the "principles" at the Taekwondo page on the Athens 2004 site. Self-defence? The "fighters" bounce on their toes, run at each other, scream, then throw some kicks that couldn't break a carton of eggs. Worse than fencing by far. Too much screaming, arms are a non factor, and the head of the federation is a crook.

DFL - Devoted to last place finishes

DFL

Tom Cochrane Big League lyrics

Doesn't anyone think that the choice of "Big League" as the theme for CBC's hockey reality show is a bit of a weird one? Kind of like when Reagan used "Born in the USA" as a patriotic theme for his campaign.


Tom Cochrane Big League lyrics

"All the right moves when he turned eighteen
Scholarship and school on a big U.S. team
Out with his girl near Lake McClean
Hit a truck doing seventy in the wrong lane
To the Big League"

Statistical Chokers

This interesting statistic from a Stephen Brunt article in the The Globe and Mail:

"The COC's chief operating officer Chris Rudge spoke of a study from the Salt Lake City Games that contained troubling, puzzling statistics about clutch performances, or the lack thereof. Of athletes ranked in the top five in the world in their event heading into the Olympics, more than half of those from the major sports nations won a medal. Canada's 'conversion rate,' on the other hand, was only 29 per cent. No one on the dais seemed to have a clue why."

So I guess Perdita's first hurdle crash isn't so unthinkable after all.

Real Women of Canada Freaking Out

The crazed blue-hairs of Real Women of Canada are pulling out their dentures over the latest Supreme Court appointments. I like how they consider giving equal rights to homsexual Canadian citizens a "bias". Evidently both of the new appointees don't think for themselves, but merely act as an echo chamber for their unshaven feminist sisters.

Perdita is the consummate Canadian

The first hurdle? Wow, no Canadian has really been that lame ... except Josee "the butt zamboni" Chouinard. I liked the Theisman like ankle twist when she landed and taking out the russian was a nice touch. The best part, just like Michael Smith who drank too much water and felt sluggish in the decathalon, we are going to fund her to train and run in another olympics four years past her peak! I think that we need to start a "let's cut our losses" campaign to cut off Perdita's funding so as to discourage her from the "one Olympic games too many" that is the hall mark of Canadian athletes.

PlayStation 2: PS2 Confidential: Case File #3

PlayStation 2: PS2 Confidential: Case File #3

Another GT4 delay? What is Sony thinking?
I believe that they are setting this game up for failure. First of all, GT4 is not a mainstream game. The level of difficulty along with the time commitment required will, I believe, put off a great many gamers. The majority of the market demand is for 'arcade' style games and not simulations. As well, sim fans have moved on to the PC and Gran Turismo sits in in an uncomfortable position halfway between sim and arcade; sim without without true to life physics and subtly and arcade without fun or flash. Also, the GT series has been out of the marketplace for so long that they are facing and uphill battle to regain recognition. Sure, Gran Turismo is familiar to the hardcore crowd, but to the average consumer, it has been nearly four years since GT3 came out. EA knows that you have keep pumping out the same title year after year to build a user base. Overly long time between versions also raises consumer expectation to unreasonable heights. If GT4 is nothing less than the greatest video game ever made than there will be disappointment.

Xbox: Winning Eleven 8 Comes to America

Xbox: Winning Eleven 8 Comes to America
I just wet my pants. Read why here...