美國(guó)愛(ài)荷華大學(xué)的研究人員發(fā)表于12月the Journal of Leukocyte Biology的研究闡明了,，為何死掉的兔熱病桿菌(或稱為法蘭西斯氏菌,，F(xiàn)rancisella tularensis能避開(kāi)人類的免疫系統(tǒng)而成為生化恐怖工具的秘密,。
兔熱病桿菌通常出現(xiàn)在北半球，可經(jīng)由蚊蟲(chóng)叮咬或接觸到受感染的動(dòng)物(如嚙齒動(dòng)物,、兔子及野兔等)而傳染,，也可經(jīng)由食物、水或空氣傳播,。Lee-Ann Allen博士指出,，過(guò)去兔熱病桿菌感染人類的機(jī)會(huì)很少，但由于恐怖份子將此菌作為生化攻擊的工具,，因此,，了解此菌對(duì)人類健康的影響變得格外重要。
自1940年代起,，兔熱病(tularemia or rabbit fever)感染的比率顯著的下降,，但此菌若被當(dāng)成生化武器就有極高的致死性，只要吸入極少量就會(huì)致死,。研究人員想要了解為何兔熱病桿菌能躲過(guò)人體內(nèi)嗜中性白血球(neutrophils)的追捕,，進(jìn)而造成人類死亡。
研究人員把兔熱病桿菌和嗜中性白血球混合,，結(jié)果發(fā)現(xiàn)嗜中性白血球能將菌體吸收,，但卻無(wú)法將菌體殺死，并發(fā)現(xiàn)兔熱病桿菌會(huì)造成嗜中性白血球的兩種防御功能喪失,，其中一種防御功能與氧有關(guān),，而另一種則與氧無(wú)關(guān)(oxygen-independent)，兔熱病桿菌能抑制這兩個(gè)防御功能的許多酵素,，在數(shù)小時(shí)后,，菌體便能逃開(kāi)嗜中性白血球的追殺，繼續(xù)進(jìn)行復(fù)制,，使受感染者致病,。
Allen博士還提醒說(shuō)，雖然兔熱病桿菌不會(huì)經(jīng)由人傳人而感染,，但卻可經(jīng)由多種感染途徑而得病，若以吸入式感染而得病,，未獲得藥物的妥善治療,，致死率相當(dāng)高。根據(jù)美國(guó)疾病管制中心(the Centers for Disease Control and Prevention,，CDC)于1990到2000年的統(tǒng)計(jì),，大約有124件疑似案例，其中60%為確認(rèn)案例,。于2001年的馬撒葡萄園島(Martha's Vineyard)也發(fā)現(xiàn)一些庭園設(shè)計(jì)師及園丁都有得到兔熱病桿菌的高風(fēng)險(xiǎn),，必須特別留意,。
英文原文：
UI Study Gives Clues About How Deadly Bacterium Gains Foothold
How a potentially deadly bacterium that could be used as a bioterrorist tool eludes being killed by the human immune system is now better understood, University of Iowa researchers report in the December issue of the Journal of Leukocyte Biology.
This bacterium, Francisella tularensis, is found naturally in the Northern Hemisphere and can be contracted through certain insect bites, contact with infected rabbits or ingesting contaminated food, water, or air.
Francisella tularensis rarely infects people. However, because the bacteria has the potential to be used as a bioterrorist tool there is increased interest in understanding how it functions, said Lee-Ann Allen, PhD, associate professor of internal medicine and microbiology at the UI Roy J. and Lucille A. Carver College of Medicine.
"The rate of tularemia or 'rabbit fever' infection has significantly declined since the 1940s. However, the bacteria would be very deadly as an aerosolized terrorist weapon -- inhaling as few as 10 bacteria could be potentially deadly," said Allen, who also is a staff researcher with the Veterans Affairs Iowa City Health Care System.
"We wanted to better understand how Francisella tularensis can overcome the body's innate immune response and cause disease. In addition, learning more about this bacterium can help us learn more about the overall human immune response to bacteria," she said.
The team focused on how Francisella tularensis evades being killed by a form of white blood cells called neutrophils. Normally, neutrophils can be quickly activated in response to infection, making them the equivalent of "first responders" for the human immune system, Allen said.
"We knew that Francisella could live inside other white blood cells called macrophages and not be killed by them," Allen said. "But little research had been done on the bacteria's survival in neutrophils.
"Early data indicated that neutrophils did not kill Francisella well. With new techniques, many of them more sensitive than in years past, we were able to look at that scenario more closely," Allen added.
The team mixed bacteria with neutrophils taken from healthy volunteers and studied the results.
"We found the neutrophils could ingest the bacteria but were not able to kill them. The Francisella somehow inhibit the ability of the neutrophils to perform two defensive functions that otherwise would kill the bacteria," Allen said.
One of the defensive functions is dependent on oxygen, and the other is oxygen-independent. Ideally, the two functions will be activated and kill the bacteria while they are trapped in a particular compartment within the neutrophils.
"The bacteria prevent these two functions from working in part by blocking the assembly of certain enzymes. After a few hours, the bacteria can escape the compartment instead of being killed, which leaves it able to replicate and cause harm," Allen said.
The researchers now seek to identify how the bacteria prevent neutrophils from mobilizing its defenses and learn more about how those defenses normally function. Additional insights could help with the eventual development of therapies or vaccines against tularemia.
A person infected with tularemia cannot pass the disease on to another person. Hunters are at an increased risk of infection if they skin an infected rabbit. Using blasts of water to clean machines, such as mowers, that have inadvertently come into contact with the carcasses of infected rabbits also can be a risk, as it makes the bacteria easy to inhale.
Allen noted that tularemia infections contracted though the skin are generally less serious to an individual. However, the inhaled form can be fatal if a person does not receive antibiotic treatment.
The Centers for Disease Control and Prevention (CDC) reported an average of 124 suspected cases of tularemia in the United States each year from 1990 to 2000, with nearly 60 percent of the cases confirmed. An investigation by the CDC into an outbreak of the disease in 2001 on Martha's Vineyard found that landscapers and gardeners who used power blowers and lawn mowers were at increased risk of being infected.
In addition to Allen, Ramona McCaffrey, PhD, UI postdoctoral research fellow in internal medicine, also contributed to the research. Both Allen and McCaffrey are members of the Division of Infectious Disease within the UI Department of Internal Medicine.
The study was supported by funds from the National Institutes of Health.
