Current Topics: Researchers Report Unusual, Seemingly Benign Bacteria in Blood
Researchers Report Unusual, Seemingly Benign Bacteria in Blood
The blood of healthy humans or other mammals is supposedly a bacteria-free zone. But several types of bacteria-some of them prodigious in their capacity to change shape-inhabit blood, apparently benignly, according to Eddie C. S. Chan from McGill University in Montreal, Marc Sirois at the University of Quebec at Trois-Rivieres, both in Quebec, Canada, and their collaborators. If confirmed, the findings have major implications, ranging from challenges associated with diagnosing illnesses and tracking antibiotic resistance to gene therapy and xenotransplantation research.
These bloodborne entities were detected initially under dark-field microscopy while Chan and his collaborators were examining blood specimens from patients with Alzheimer's disease, he says. Surprised with these observations, they similarly examined blood samples from healthy subjects using microscopy but also "molecular phylogenetic techniques and...other conventional microbiological methods." Those efforts consistently uncovered evidence of a variety of bacteria in blood, including several that are closely related to Pseudomonas and to a similar bacterium called Stenotrophomonas maltophilia. These species identifications are based on 16S ribosomal RNA gene analyses detailed in the Journal of Clinical Microbiology (40:4771-4775, 2002).
Similar bacteria also can be detected in blood from pigs, according to Sirois. Such prokaryotic inhabitants of the blood may play a role in disseminating antibiotic resistance, especially if the same microbes that appear to be circulating in humans also inhabit the circulatory systems of livestock, he says. And, says Chan, "There are many unexplained diseases that cannot be pinpointed to any specific cause, such as arthritis, where these bacteria might be involved."
At least as long ago as 1969, other researchers also reported finding benign, blood-dwelling bacteria. More recently in 2001, David Relman and Simo Nikkari of Stanford University in Stanford, Calif., and their collaborators reported detecting bacterial-like ribosomal DNA sequences in blood samples. Such findings invoke both fascination but also skepticism, even among those directly involved in studying some of these blood specimens. One big concern is that members of his group and other investigators are identifying contaminants rather than bacteria that really are living in blood, according to Relman.
"We know there are Pseudomonas-related 16S ribosomal DNA sequences that you can recover from PCR reagents," Relman points out. Nonetheless, he adds, "This is tantalizing. I think we are just scratching the surface of what might be present in the bloodstream of healthy people." As detection methods become increasingly sensitive, determining whether seeming inhabitants of blood are clinically relevant or mere contaminants will become an ever-greater challenge, he says.
Several results provide further evidence that these entities are viable bacteria, not artifacts, according to Chan. For instance, antibiotics such as polymyxin B and bacitracin affect the behavior of these entities in blood samples, the former rendering most of them "lifeless," he says. However, the bacteria do not grow on various media in the laboratory, which is "not surprising," he says. "99% of all the microorganisms in the world cannot be cultivated on the artificial media we use in the laboratory." Intriguingly, the bacteria change shape, shifting from rods to spheres within 5 to 7 minutes, he adds. "We followed it by time-lapse photography. It's amazing an organism could do this kind of metamorphosis at such a rapid rate."
"I would not be surprised if they [the investigators in Canada] are correct based on their data, the data they cite, and our growing recognition that as more sensitive molecular detection techniques are brought to bear we find more and more 'normal flora' in well people, in addition to describing the microbial causes for long-recognized illnesses," says Louis Katz, who is medical director of the Mississippi Valley Regional Blood Center in Davenport, Iowa, and president-elect of America's Blood Centers. However, he calls their evidence "thin."
Despite uncertainty about whether seemingly benign bacterial actually are circulating in blood, Chan says that several biotechnology companies have expressed interest in his work. "The bacteria could be used as vectors for carrying genes, drugs, or markers for therapy in the human host without harming the host," he says. "We can isolate them, label them with some therapeutic drug, and put them back in." Nonetheless, important questions will need to be resolved before these supposed blood-dwelling bacteria could be used as vectors or for other medical interventions. In particular, it is critical to learn whether they are benign or harmful.
Questions of microbial ecology also need to be addressed, according to Relman. "You want to know if you are dealing with organisms that are persistent members of that compartment [the bloodstream] rather than a transient that stumbles in and will get cleared in a few minutes," he says. "My hope is that people will confirm these sorts of findings and develop the database."
David Holzman David Holzman writes from Lexington, Mass.
Posts: 559 | From Cary, NC | Registered: May 2006
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Lyme Disease: a Potential Polymicrobial Infection Brogden and Guthmiller present a provocative overview of polymicrobial diseases (ASM News, February 2003, p. 69-73). Surprisingly, they fail to mention an excellent example of potential polymicrobial infection: Lyme disease.
In the United States, Lyme disease is caused by infection with the spirochete Borrelia burgdorferi, which is transmitted to humans by the bite of ixodid ticks. These tiny ticks, which have been called sewers of infectious disease, carry and transmit numerous additional pathogens, including Babesia species, the agents of human granulocytic and monocytic ehrlichiosis, the agent of tularemia Franciscella tularensis, and the most recently recognized tickborne pathogen, Bartonella henselae. Numerous studies have documented polymicrobial infection following a tickbite (A. Doherty, www.geocities.com/HotSprings/Oasis/6455/lyme-links.html;S. J. De Martino, J. A. Carlyon, and E. Fikrig, N. Engl. J. Med. 345:150-151, 2001; E. Eskow, R. V. Rao, and E. Mordechaim, Arch. Neurol. 58:1357-1363, 2001). Serologic analysis from a Lyme vaccine trial showed that 26% of patients who developed complex symptoms of Lyme disease had evidence of coinfection with Babesia microti or Anaplasma phagocytophila, the agent of human granulocytic ehrlichiosis (A. C. Steere, A. Dhar, J. Hernandez, P. A. Fischer, V. K. Sikand, R. T. Schoen, J. Nowakowski, G. McHugh, and D. H. Persing, Am. J. Med. 114:58-62, 2003). A study from California found that 23.5% of patients with Lyme disease had evidence of coinfection with the Babesia WA-1 strain in that state (R. B. Stricker, N. S. Harris, D. C. Yong, and E. E. Winger, J. Invest. Med. 51(Suppl. 1):S145, 2003). Thus, tickborne polymicrobial infection is relatively common in patients with Lyme disease.
Treatment of Lyme disease has been controversial due to the perception that the disease is hard to catch and easy to cure (A. Doherty, www.geocities.com/HotSprings/Oasis/6455/lyme-links.html). As suggested in Table 3 of the article by Brogden and Guthmiller and in a mouse model of Lyme disease (V. Thomas, J. Anguita, S. W. Barthold, and E. Fikrig, Infect. Immun. 69:3359-3371, 2001), coinfection may promote resistance to standard antimicrobial therapy by various mechanisms, thereby altering the clinical course of Lyme disease and necessitating extended therapy for coinfected patients (R. Bransfield, S. Brand, and V. Sherr, N. Engl. J. Med. 345:1424-1425, 2001; A. Lautin, E. L. McNeil, K. B. Liegner, R. B. Stricker, and L. H. Siga, Ann. Intern. Med. 137:775-777, 2002). The issue of optimal therapy for Lyme disease patients with polymicrobial infection requires further study.
Raphael B. Stricker California Pacific Medical Center San Francisco, Calif. [email protected]
Benign Bacteria in Blood
I am writing in response to the article entitled ``Researchers report unusual, seemingly benign bacteria in blood'' (ASM News, February 2003, p. 60-62).
Viable bacteria in blood are common among people who have long-lasting wounds that are open to the bloodstream. The most common type of wound is inflammation of the gums (periodontitis) and it is not unusual to find throat flora, such as alpha hemolytic and nonhemolytic streptococci and BORRELIA species in the blood of these people. The picture shown in this article on p.61 is most likely BORRELIA. The article also mentioned Stenotrophomonas maltophilia which is also a bacteria found in the throat.
Another type of open wound is ulcerative colitis in which the surface of the colon is exposed to fecal matter. It would be surprising if some fecal bacteria did not get into bloodstream of these people once in a while. I think this type of bacteremia would be common among populations with poor oral hygiene or frequent intestinal infections that cause ulceration of the colon. Among normal, healthy people, even small surgical procedures on the digestive tract, extraction of teeth, removal of tonsils, and hemorrhoidectomies can be expected to produce bacteremia because these places normally contain a large number of bacteria. Blood samples taken soon after these procedures can contain bacteria that inhabit these localities. I just hope that people won't spend too much time reinventing wheels. This writer used to work in the Department of Bacteriology of the 406th Medical General Laboratory of the U.S. Army located in Tokyo from 1947 to 1954. We isolated many throat flora from the blood of people with poor oral hygiene or cases of Vincent's angina, which is caused by a combination of BORRELIA vincenti and Bacterioides species (a gram-negative anaerobic bacillus).
Pinghui V. Liu 533 NE Wavecrest Ct. Boca Raton, Fla.
Correction
In the April 2003 issue on p. 197, Kenneth H. Nealson's nominator for the Procter & Gamble Award in Applied and Environmental Microbiology, John Lennox, is incorrectly identified as a Fellow of the American Academy of Microbiology. ASM News regrets the error.
Posts: 559 | From Cary, NC | Registered: May 2006
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posted
Very interesting. I wonder, though, why they were so quick to describe these bacteria in the blood as benign.
Posts: 8430 | From Not available | Registered: Oct 2000
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posted
Very good question. I think they were quick to dismiss that because it goes against conventional wisdom rather than say, they have proven that theory scientifically.
Posts: 559 | From Cary, NC | Registered: May 2006
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posted
What I found interesting was how they described bacteria that were able to morph ie: change appearance, and were not recognizeable until they were PCR'ed.
Sounds an awefull lot like the same thing Dr. Phillips said in his paper about a reliable culture for Lyme Disease based upon mophologically different forms of Borrelia Burgdorferri.
Posts: 559 | From Cary, NC | Registered: May 2006
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