Leptospirosis outbreak among strawberry harvesters in Germany

Humans can become infected with the spirochete Leptospira if they have wounds that contact contaminated soil or water. Leptospira live in the kidneys of reservoir animals and are released in urine into the environment. The majority of leptospirosis cases occurs in tropical locales, where the warm, moist conditions promote the survival of Leptospira in the environment. Flooding following heavy rainfall can cause large epidemics of leptospirosis in these regions of the world. A research article published in the March 15th issue of Clinical Infectious Diseases by Desai and colleagues describes an unexpected outbreak of leptospirosis among strawberry harvesters in Germany, a country not known for tropical weather. The July 2007 outbreak, while small by the standards of those that occur in tropical countries, was Germany's largest since the 1960s. The authors searched for factors that may have caused the epidemic.

The outbreak occurred among laborers who worked on a strawberry farm near Düren. The strawberry harvesters were seasonal workers from Romania, Slovakia, and Poland. Among the 153 who were employed on the farm during the outbreak, 24 were stricken with leptospirosis, and 13 were hospitalized. Fortunately, no one died. Most who became sick had antibodies against the Leptospira serogroup Grippotyphosa in their blood.

In September 2007, the authors conducted a retrospective cohort study to identify risk factors for acquiring leptospirosis. The strawberry harvesters were questioned about possible sources of exposure to Leptospira before the outbreak, including the presence of wounds, contact with rodents, and consumption of unwashed strawberries. Logistic regression of the data revealed two statistically significant risk factors. First, the odds of the harvesters acquiring leptospirosis increased with the number of days worked with unprotected hand lesions (OR, 1.1; 95% CI, 1.04-1.1). Leptospira probably entered the lesions as the workers reached into the water-logged soil. "Accidental contact with rodents" was listed as the other significant risk factor (OR, 4.8; 95% CI, 1.5-15.9), although the nature of the contact was not described by the authors. Of course recall bias may have skewed the results of the retrospective study. However, there is nothing unusual about these risk factors; contact of skin wounds with moist soil laden with Leptospira and exposure to infected rodents are typical means of acquiring leptospirosis.

The common vole was the main suspect in contaminating the strawberry field with Leptospira. More than 10 mouse holes per square meter were found in the field and surrounding areas when the site was examined in September 2007. Kidneys of voles captured in and near the field were infested with the spirochete. Leptospira was successfully cultured from the kidneys and were identified as members of the serogroup Grippotyphosa, the same serogroup that the antibodies in the patients' blood were targeting.

The strawberry field outbreak is reminiscent of the large epidemics of leptospirosis that sickened thousands of German agriculture workers from the 1920s through the 1960s, with the Leptospira serogroup Grippotyphosa carried by voles and hamsters responsible for many cases. In contrast, most German cases of leptospirosis of late are related to activities outside of work. Recreational activities involving water and exposure at home to infected pets and contaminated soil while gardening are common risk factors. Icterohaemorrhagiae, with rats as the reservoir host, is now the most prevalent serogroup in Germany. So why did a 1960s-style leptospirosis outbreak occur in 2007? The authors propose that the unusual weather in the months preceding the outbreak was a critical factor.

Europe experienced its warmest autumn in 2006 since recordings began, and the warm weather continued through the winter into 2007. In Germany, heavy rainfall accompanied the high temperatures in the months preceding the outbreak. May and June 2007 were Germany's wettest months since 1901. The tropical conditions may have augmented the amount of food available to the voles. In addition, the vole population, which naturally fluctuates every 3-5 years, may have already been at the peak of its cycle in 2007. A population explosion of infected voles may have increased the density of Leptospira residing in the strawberry field. Because the wet, warm conditions were favorable to survival of Leptospira, it is easy to imagine how an outbreak would have occurred among workers who spent days reaching into the contaminated soil with unprotected hands.

In conclusion, the authors present leptospirosis as a potential model for an infectious disease affected by global warming. Only time will tell whether the leptospirosis outbreak caused by the confluence of warm weather and heavy rainfall in a normally temperate region was a statistical anomaly or a sign of things to come.

Featured paper

Desai, S., van Treeck, U., Lierz, M., Espelage, W., Zota, L., Sarbu, A., Czerwinski, M., Sadkowska‐Todys, M., Avdicová, M., Reetz, J., Luge, E., Guerra, B., Nöckler, K., & Jansen, A. (2009). Resurgence of Field Fever in a Temperate Country: An Epidemic of Leptospirosis among Seasonal Strawberry Harvesters in Germany in 2007 Clinical Infectious Diseases, 48 (6), 691-697 DOI: 10.1086/597036

Other references

Jansen, A., Schöneberg, I., Frank, C., Alpers, K., Schneider, T., and Stark, K. (2005). Leptospirosis in Germany, 1962-2003. Emerging Infectious Diseases 11(7):1048-1054.

Pappas, G., Papadimitriou, P., Siozopoulou, V., Christou, L., Akritidis, N. (2008). The globalization of leptospirosis: worldwide incidence trends. International Journal of Infectious Diseases 12(4):351-357.

Rhesus monkeys with Lyme spirochetes in the brain

Lyme disease has been mentioned in the news a lot lately. First it was a pet chimp mauling his neighbor last month in a Connecticut town. Many news accounts of the assault reported that Travis the chimp suffered from Lyme disease and had been given tea laced with Xanax to calm his erratic behavior prior to the attack. Investigators may never figure out what provoked Travis to attack Charla Nash. Was Lyme disease a factor? Maybe (although if I had to guess, it had more to do with a wild animal being kept as a pet, living where it didn't belong).

This past weekend a human reportedly suffering from long-term Lyme disease gunned down a pastor and injured several parishioners in an Illinois church. As with any topic having to do with chronic Lyme disease, experts disagree on whether Lyme disease can trigger aggression (but I'm pretty sure what the shooter's defense attorney believes). One prominent researcher even questions whether the alleged shooter truly had Lyme disease.

A blogger on Forbes.com doubts whether chimps could be stricken with Lyme disease. In reality, seeing a chimp with Lyme disease should not surprise us at all since another nonhuman primate, the rhesus monkey, has been used for years to study neuroborreliosis, the form of Lyme disease caused by infection of the nervous system. Neuroborreliosis is observed in up to 15% of untreated Lyme disease patients. I will present two studies in which scientists examined infection of the central nervous system of rhesus monkeys by the Lyme disease spirochete, Borrelia burgdorferi.

In a 2000 study by Cadavid and colleagues, the investigators found small numbers of spirochetes in the meninges and spinal cord nerve roots of rhesus monkeys four months following laboratory infection with B. burgdorferi by needle inoculation into the skin (see figure below). In humans, the inflammatory response to the spirochetes in the meninges and nerve roots can cause meningitis (headache, stiff neck, and sensitivity to light) and radiculoneuritis (shooting pains and abnormal skin sensations), respectively.

Figure 2b from Cadavid et al., 2000. A single B. burgdorferi cell in the anterior nerve root stained by immunohistochemistry with anti-B. burgdorferi antibodies.

The investigators found no convincing evidence for the presence of B. burgdorferi in the brain parenchyma of the infected rhesus monkeys. B. burgdorferi was not found in the brain by microscopy. On the other hand, B. burgdorferi DNA was detected in brain tissue by polymerase chain reaction (PCR). This result may suggest that the spirochete is present in the brain at low levels, although the authors believed that spirochetes in the meninges surrounding the brain was the real source of the DNA. It's also possible that the N40 B. burgdorferi strain used by the authors was incapable of invading the brain of rhesus monkeys and that another strain if injected into the skin would have found its way to the brain.

Two conditions associated with neuroborreliosis disrupt brain function in humans. The first is Lyme encephalopathy, which can cause fatigue and problems with concentration and memory. Brain activity is clearly affected in patients with Lyme encephalopathy, yet the underlying pathogenic mechanism remains an enigma. Many patients with this potentially disabling condition do not exhibit the classic signs of central nervous system inflammation such as the presence of white blood cells in their cerebral spinal fluid (CSF), production of antibodies against the infective agent in the CSF, or abnormal brain MRIs. Some neuroborreliosis experts have proposed that these cases of Lyme encephalopathy are a result of "toxic-metabolic" effects of infection elsewhere in the body (such as Lyme arthritis in the joints) spilling into the brain. Nevertheless, a low-level infection of the brain by B. burgdorferi cannot be ruled out. More obvious brain involvement is observed in neuroborreliosis patients with encephalitis, in whom brain lesions are detected by MRI, accompanied by white blood cells and production of anti-B. burgdorferi antibodies in the CSF. Symptoms include slight weakness or paralysis affecting one side of the body, spastic muscles, inability to feel sensations, and bladder dysfunction. In rare cases, patients may experience strokes or seizures. Patients with encephalitis are likely to have spirochetes in their brain, usually near blood vessels.

Lyme disease may also be associated with psychiatric illness, particularly depression. Rare cases of panic attacks, bipolar disorder, mania, obsessive-compulsive disorder, dementia, and violent outbursts have also been reported.

A recent study by Mario Philipp's group in Tulane, published recently in The American Journal of Pathology, described the potential effects of B. burgdorferi on brain cell activity of rhesus monkeys. Spirochetes injected into the skin with a needle or by tick bite are unable to make it into the brain of rhesus monkeys, as I explained above. Therefore, the investigators injected live B. burgdorferi spirochetes directly into the right side of the brains of rhesus monkeys. After two weeks, they found that an average of ~10% of oligodendrocytes at the injection sites had undergone death by apoptosis, as detected by fluorescent TUNEL staining (see figure below). In contrast, fewer than 2% of oligodendrocytes underwent apoptosis when sites in the left side of the brain of the same animals were injected with saline. Oligodendrocytes produce the myelin sheaths that surround the axons of neurons and promote transmission of electric impulses; one would expect the loss of oligodendrocytes to affect neuron function.

The in vivo results corroborated ex vivo experiments in which brain slices from rhesus monkeys were incubated with B. burgdorferi for up to eight hours. In the ex vivo experiments, apoptosis of both oligodendrocytes and neurons were detected by fluorescent TUNEL staining and with antibody against activated caspase 3, a more specific marker of apoptosis. The authors speculated that neurons undergoing apoptosis in vivo were removed by phagocytes and therefore went undetected in the brain injection experiment. The other major brain cell types, microglial cells and astrocytes, were spared from apoptotic death both ex vivo and in vivo.

Figure 4A from Ramesh et al., 2008. Oligodendrocytes are stained red with antibody to S-100. Nuclei of cells undergoing DNA fragmentation, a consequence of apoptosis, are TUNEL stained green. When the images are merged, the nuclei of oligodendrocytes undergoing apoptosis become yellow. B. burgdorferi, which are stained in blue, do not appear to be in physical contact with the oligodendrocytes.

Figure 4B from Ramesh et al., 2008. Percentage of oligodendrocytes undergoing apoptosis from 3 sites of spirochete (A-C) and saline (D-F) injections (click on image for larger view).

The Tulane group also detected myriad cytokines and chemokines such as IL-6, IL-1ß, and CXCL13 being produced in the B. burgdorferi-treated brain slices by immunofluorescence antibody staining and DNA microarray analysis. The authors concluded that B. burgdorferi invasion of the brain elicits production of a brew of inflammatory mediators that promote apoptotic death of oligodendrocytes and neurons. It may be true that brain invasion by B. burgdorferi in cases of human neuroborreliosis leads to production of these cytokines and chemokines, as IL-6, IL-1ß, and CXCL13 have been detected in the CSF of neuroborreliosis patients in earlier studies. However, the apoptotic cells observed by the Tulane group may be the unnatural consequence of small areas of the brain being exposed to extremely large numbers of spirochetes. Each site was injected with 5,000 spirochetes, a number far greater than the rare spirochetes observed by microscopy in the brains of neuroborreliosis patients. For the ex vivo experiments, a 2-mm section of brain was incubated with 20 million spirochetes, again a large burden of bacteria. More convincing would be finding apoptosis of oligodendrocytes and neurons in brain tissues in patients with Lyme encephalitis. Clearly more studies are needed to understand the events that really occur when B. burgdorferi invades the brain.

References

Ramesh, G., Borda, J., Dufour, J., Kaushal, D., Ramamoorthy, R., Lackner, A., & Philipp, M. (2008). Interaction of the Lyme Disease Spirochete Borrelia burgdorferi with Brain Parenchyma Elicits Inflammatory Mediators from Glial Cells as Well as Glial and Neuronal Apoptosis American Journal Of Pathology, 173 (5), 1415-1427 DOI: 10.2353/ajpath.2008.080483

Diego Cadavid, Tim O'Neill, Henry Schaefer, and Andrew R. Pachner (2000). Localization of Borrelia burgdorferi in the Nervous System and Other Organs in a Nonhuman Primate Model of Lyme Disease Laboratory Investigation, 80 (7), 1043-1054

Viewing the arrangement of Borrelia burgdorferi flagella by electron cryotomography

The most peculiar feature of spirochetes may be the location of their flagella, the thin motility structures that propel bacteria through liquids. Flagella typically extend out from the surface of bacteria into the surroundings. Spirochetes, being not so typical, keep their flagella hidden in the periplasm between the cytoplasmic and outer membranes (see figure). For example, the Lyme disease spirochete Borrelia burgdorferi has 7-11 flagella attached near each end of the "protoplasmic" or cell cylinder, with each flagellum extending through the periplasm towards the center of the spirochete. The flagella impose a flat-wave shape (not a spiral shape!) on B. burgdorferi by wrapping around its protoplasmic cylinder.

from Rosa et al., 2005

How do flagella that are located in the periplasm drive the spirochete through the medium? B. burgdorferi motility is thought to require the rotation of its flagella against the cell cylinder, causing the cell body to gyrate.

B. burgdorferi flagella often appear as a bundle when observed by standard transmission electron microscopy. Here is one such image from a 2000 study revealing at least 10 flagella in a cross section of B. burgdorferi. With the flagella arranged in this manner, it is difficult to imagine how the flagella that are not in direct contact with the cell cylinder could contribute to its gyration.

A study by Charon and colleagues in the January 2009 issue of Journal of Bacteriology suggests that the flagellar bundle is an artifact of the standard techniques used to prepare the samples for electron microscopy. They employed the emerging technique of electron cryotomography to avoid the fixation and staining procedures that often introduce artifacts into samples. Electron cryotomography consists of the following steps:

1. To preserve structure, the specimen is plunge frozen at -165°C or less. Fixing or staining is not necessary.
2. While maintaining the sample at the ultralow temperature, 2D projections of the sample are obtained at different angles by transmission electron microscopy.
3. Computer software assembles the 3D structure of the specimen from the 2D projections.

The software also permits slices of the specimen to be observed without having to actually perform thin sectioning.

Here's a cross-section of B. burgdorferi as viewed by electron cryotomography. Note that the flagella are arranged in a single layer within the periplasm, not in a bundle.

Figure 1 of Charon et al. Bar, 50 nm.
PFs, periplasmic flagella; PS, periplasmic space; PM, plasma (or cytoplasmic) membrane; OM, outer membrane.

A longitudinal slice through the periplasm of B. burgdorferi reveals nine flagella neatly arranged in a parallel fashion along the surface of the protoplasmic cylinder. The authors refer to this array as a "flat ribbon." Each flagellum in the ribbon is separated by ~3 nm, allowing each to rotate in the same direction without interference from neighboring flagella.

Figure 5 of Charon et al. Bar, 200 nm.

3D reconstruction of a section of the spirochete illustrates the flat ribbon of flagella (in red) wrapping around the cell cylinder (in blue). Only a section of the cell cylinder is shown, and the outer membrane has been removed from the image.



These new images support a model for for B. burgdorferi motility that was first described back in the 1990s. In this model, the rotation of the flagella against the cell cylinder generates gyrating waves that progress backwards along the cell body. As explained in the discussion of the Charon et al. paper, it is conceivable that all 7-11 flagella must lie against the cell cylinder as a flat ribbon to exert the force necessary to generate the waves; a flagella bundle may not exert enough force. The torque generated by the rotating flagella causes a counter rotation of the cell cylinder (panel a below). The backward-propagating, gyrating waves push the spirochete through the medium. Flagella arranged in a bundle would not generate enough torque because of potential interference between rotating flagella (panel b).

Figure 8 of Charon et al. a. Flagella arranged in a flat ribbon. b. Flagella arranged in a bundle.

This model also explains why B. burgdorferi moves so well through viscous gel-like material such as the extracellular matrix; the gel provides traction for the backward-progressing waves to drive the spirochete through the medium.

Here's a movie animating B. burgdorferi motility, first presented at a meeting in 2001 .


SOURCE

You can also see real B. burgdorferi gyrating and generating backward-moving waves in a movie embedded in Dr. Nyles Charon's website.

Reference

N. W. Charon, S. F. Goldstein, M. Marko, C. Hsieh, L. L. Gebhardt, M. A. Motaleb, C. W. Wolgemuth, R. J. Limberger, N. Rowe (2009). The Flat-Ribbon Configuration of the Periplasmic Flagella of Borrelia burgdorferi and Its Relationship to Motility and Morphology Journal of Bacteriology, 191 (2), 600-607 DOI: 10.1128/JB.01288-08

The Lyme disease spirochete hijacks fibronectin to escape from the bloodstream

The glycoprotein fibronectin is a component of the molecular mesh known as the extracellular matrix, which not only provides physical support for our cells but also directs cellular activities during embryonic development, tissue repair, and other processes. High levels of soluble fibronectin (300 μg/ml) are also found in our bloodstream, where it quietly circulates until it is recruited to stabilize clots and promote wound repair.

Fibronectin has a modular organization consisting of binding sites for various matrix and cell surface molecules. Examples include attachment sites for integrins (labeled "Cell" in the figure below) and glycosaminoglycans (labeled "Heparin"), which are exposed on the surface of the endothelial cells that line our blood vessels.

from Wierzbicka-Patynowski, 2003

B. burgdorferi is injected into the skin by an infected tick and spreads outward within the dermis, causing the familiar "bulls-eye" rash in some Lyme disease patients. The spirochete may eventually enter the bloodstream so that it can spread to other tissues. While in the bloodstream, the spirochete is surrounded by fibronectin. In fact, B. burgdorferi attaches to fibronectin in vitro, suggesting a role for fibronectin in Lyme disease.

It turns out that B. burgdorferi exploits the adhesive properties of plasma fibronectin to bind to the vessel wall before escaping into the surrounding tissue. Like their earlier work, which I described in my last post, this follow-up study by Norman and colleagues was conducted with fluorescent B. burgdorferi injected into the veins of live mice. The interactions of the spirochete with the capillary wall were observed by fluorescent intravital microscopy. The earlier study revealed that most of the interactions were transient, lasting for less than a second. B. burgdorferi was also seen crawling (dragging) along the vessel wall, which was followed by escape into the tissue or by stationary adhesion, a more intimate association with the vessel wall. Stationary adhesion could also be followed by extravasation and escape of the spirochete into the tissue. Both stationary adhesion and escape usually occurred between the endothelial cells lining the vessel wall. Each type of interaction (transient, dragging, and stationary adhesion) was quantitated by counting.

In their follow-up study, the authors demonstrated that coinjection of anti-fibronectin antibody and B. burgdorferi into the bloodstream of the mice diminished all catagories of interactions (transient, dragging, and stationary adhesion) by at least 90%. Control antibody (goat IgG) had no effect. These results indicate that fibronectin has a key role in mediating the attachment of B. burgdorferi to the microvasculature. Since fibronectin could potentially bind to GAGs and integrins on endothelial cells, the investigators also coinjected B. burgdorferi with peptides or antibodies known to block attachment of fibronectin to these targets. They found that the GAG-specific peptide reduced the interaction of B. burgdorferi with the vessel wall, whereas the integrin-specific peptide and antibodies had little effect. Thus, fibronectin may serve as a molecular bridge linking B. burgdorferi to GAGs displayed on the endothelial cells lining the blood vessel.

Which B. burgdorferi factor is involved in adherence to the vessel wall in vivo? Past studies had shown that the borrelial protein BBK32, a known fibronectin binding protein, mediated attachment of B. burgdorferi to fibronectin in vitro. Therefore, BBK32 was a logical candidate. To determine whether BBK32 was involved in vascular interactions in the mouse model, the research team employed a noninfectious B. burgdorferi strain that had lost bbk32 and other genes during long-term culture. The noninfectious strain failed to interact with the vasculature in the mouse. However, expression of BBK32 restored the ability of the noninfectious strain to transiently interact and drag along the vessel wall but only partly restored stationary adhesion. This results suggest that although BBK32 plays a role in vascular adherence, other bacterial factors are also involved.

Many pathogens have been shown to interact with fibronectin and GAGs in vitro. However, this study is highly significant as it is the first to demonstrate a role for these host molecules in bacterial adherence to the microvasculature in a living animal. Other spirochetes such as Treponema pallidum and Leptospira also express fibronectin binding proteins. Hence, the mechanism employed by B. burgdorferi to escape from the bloodstream may be similar for all disease-causing spirochetes. Moreover, other microbial pathogens have been shown to stick to fibronectin and GAGs in vitro. Thus, a large number of invasive pathogens may employ similar mechanisms to spread to different tissues via the bloodstream.

M. Ursula Norman, Tara J. Moriarty, Ashley R. Dresser, Brandie Millen, Paul Kubes, George Chaconas (2008). Molecular Mechanisms Involved in Vascular Interactions of the Lyme Disease Pathogen in a Living Host PLoS Pathogens, 4 (10) DOI: 10.1371/journal.ppat.1000169

Watch videos of the Lyme disease spirochete escaping from the bloodstream of live mice!

Most pathogenic microbes that cause systemic infections, regardless of their route of host entry, migrate to the circulatory system, which facilitates their spread throughout the body. These invasive microbes, which include the Lyme disease spirochete B. burgdorferi, eventually exit the bloodstream and penetrate into various organs of the host. Last June in the online journal PLoS Pathogens, a Canadian research group presented some fascinating microscopic video footage of Borrelia burgdorferi traveling within and escaping from the bloodstream of live mice. We may like to think that the unique shape of the spirochete allows it to simply drill through the vessel wall, but the videos suggest that escape from the bloodstream is a little more complex.

Because spirochetes are too thin to observe by light microscopy, Moriarty and colleagues made B. burgdorferi fluoresce by transforming the spirochete with a gfp (green fluorescent protein) plasmid. To prepare the animals, they lifted the skin of anesthetized mice for observation of the underlying dermal microvasculature by fluorescence intravital microscopy (IVM), which allows visualization of cellular events in a living animal. They next injected the fluorescent spirochetes into the bloodstream of the mice, and they examined dermal postcapillary venules under the microscope as the spirochetes traveled through the field of view within the vessels.

The black-and-white video reveals several types of interactions between the spirochetes and vessel wall. The bar graph displayed below the video indicates the proportion of each type of interaction observed. Almost 90% of the contacts are transient, lasting for less than a second. About 10% of the interactions involved crawling or dragging of the spirochete along the vessel wall for up to 20 seconds. As you can see from the bar graph, these short-term interactions, although common, rarely lead to escape of spirochetes from the bloodstream. Perhaps the spirochetes crawl along the wall probing for an escape route from the vessel. When their search fails, as it usually does, they detach and float (or swim) away and try again elsewhere along the vessel wall. Occasionally, a spirochete will remain stuck to the vessel wall for many minutes. One such spirochete can be seen in the video, near the center of the screen. More careful observation of stationary spirochetes in the bloodstream of several mice revealed at least one end deeply embedded with the vessel wall, usually between endothelial cells. It is unclear whether these stationary adhesions are a necessary prelude to exit of the spirochete of the vessel as consistent outward movement of embedded spirochetes was never observed during the observation period, which lasted up to 45 minutes.



The next two videos capture spirochetes in the process of escaping from the bloodstream. The endothelium was stained by injecting the bloodstream with red fluorescent antibody to PECAM-1, a protein found within endothelial junctions. The first video shows how difficult it is for B. burgdorferi to traverse the wall of the venule. The spirochete appears to be stuck as it moves back and forth (reciprocal translation) across the vessel wall for several minutes trying to free itself. The second video shows a spirochete successfully dislodging itself and fleeing from the venule. The average escape time was 10.8 minutes (N = 11 spirochetes). The authors could not clearly determine whether the spirochetes escaped between or through endothelial cells.





Here's the model illustrating the steps in the escape of B. burgdorferi from the bloodstream. The spirochete first contacts and crawls (drag) across the inside surface of the vessel wall. It then crosses the vessel wall end-first. After a long period of back-and-forth motion (reciprocal translation), the spirochete finally escapes into the tissue. It is unknown whether stationary adhesion is necessary for escape.


Moriarty et al. repeated the experiments with B. burgdorferi rendered noninfectious by long-term passage in culture. They found minimal interaction of noninfectious spirochetes with the vessel wall, and not a single spirochete could be found escaping from the bloodstream. This result indicates that specific Borrelia surface molecules that are missing on noninfectious B. burgdorferi mediate interaction with and escape from the bloodstream. What are these B. burgdorferi surface molecules, and which host molecules do they contact in the blood vessel? Past in vitro experiments with cultured mammalian cells by several research groups have revealed a few candidates for such bacterial and host factors. The authors described the roles of these candidates in transient, dragging, and stationary adhesions in live mice in a follow-up study, which I will write about in my next post.

Featured paper

Tara J. Moriarty, M. Ursula Norman, Pina Colarusso, Troy Bankhead, Paul Kubes, George Chaconas (2008). Real-Time High Resolution 3D Imaging of the Lyme Disease Spirochete Adhering to and Escaping from the Vasculature of a Living Host. PLoS Pathogens, 4 (6) DOI: 10.1371/journal.ppat.1000090