美国爱荷华大学的研究人员发表于12月the Journal of Leukocyte Biology的研究阐明了,为何死掉的兔热病杆菌(或称为法兰西斯氏菌,Francisella tularensis能避开人类的免疫系统而成为生化恐怖工具的秘密。
兔热病杆菌通常出现在北半球,可经由蚊虫叮咬或接触到受感染的动物(如啮齿动物、兔子及野兔等)而传染,也可经由食物、水或空气传播。Lee-Ann Allen博士指出,过去兔热病杆菌感染人类的机会很少,但由于恐怖份子将此菌作为生化攻击的工具,因此,了解此菌对人类健康的影响变得格外重要。
自1940年代起,兔热病(tularemia or rabbit fever)感染的比率显著的下降,但此菌若被当成生化武器就有极高的致死性,只要吸入极少量就会致死。研究人员想要了解为何兔热病杆菌能躲过人体内嗜中性白血球(neutrophils)的追捕,进而造成人类死亡。
研究人员把兔热病杆菌和嗜中性白血球混合,结果发现嗜中性白血球能将菌体吸收,但却无法将菌体杀死,并发现兔热病杆菌会造成嗜中性白血球的两种防御功能丧失,其中一种防御功能与氧有关,而另一种则与氧无关(oxygen-independent),兔热病杆菌能抑制这两个防御功能的许多酵素,在数小时后,菌体便能逃开嗜中性白血球的追杀,继续进行复制,使受感染者致病。
Allen博士还提醒说,虽然兔热病杆菌不会经由人传人而感染,但却可经由多种感染途径而得病,若以吸入式感染而得病,未获得药物的妥善治疗,致死率相当高。根据美国疾病管制中心(the Centers for Disease Control and Prevention,CDC)于1990到2000年的统计,大约有124件疑似案例,其中60%为确认案例。于2001年的马撒葡萄园岛(Martha's Vineyard)也发现一些庭园设计师及园丁都有得到兔热病杆菌的高风险,必须特别留意。
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.