Spirochetes Unwound

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This blog highlights the research being done on those twisty bacteria known as spirochetes.

Microbe Fan
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  • November 12, 2015
  • 02:45 AM

Lighting up Leptospira interrogans to test antibiotic treatment of chronically-infected mice

by Microbe Fan in Spirochetes Unwound

A group at the Pasteur Institute succeeded in generating a bioluminescent strain of Leptospira interrogans.  Their study was published last year in PLOS Neglected Tropical Diseases.The benefit of having a bioluminescent strain is that infections of small laboratory rodents can be monitored without sacrificing the animals.  Instead, the animals are placed in a special whole-body imager that detects light emitted from the bodies.  The location of the infection in the animals can be ........ Read more »

  • September 6, 2015
  • 09:28 PM

Do Lyme disease spirochetes produce a toxin?

by Microbe Fan in Spirochetes Unwound

According to the current view of Lyme disease pathogenesis, tissue damage is caused by the inflammatory response to the spirochetes.  Borrelia species do not produce toxins that injure the host directly.  A new study published in BMC Microbiology may force us to modify our view.The study shows that some Borrelia strains carry a set of genes with the potential to generate a peptide resembling streptolysin S (SLS), a potent toxin produced by the pathogen Streptococcus pyogenes.  The........ Read more »

Molloy EM, Cotter PD, Hill C, Mitchell DA, & Ross RP. (2011) Streptolysin S-like virulence factors: the continuing sagA. Nature Reviews Microbiology, 9(9), 670-81. PMID: 21822292  

  • August 18, 2015
  • 12:18 AM

A biosignature of early Lyme disease

by Microbe Fan in Spirochetes Unwound

Laboratory testing for Lyme disease involves two-tier antibody testing with sera from patients suspected of having the disease.  The first step is usually an ELISA with a cell lysate of Borrelia burgdorferi as antigen.  If the ELISA results are positive or borderline, a Western blot is done to confirm that the patient has Lyme disease.  Direct detection of Borrelia burgdorferi by culture would be the preferred laboratory test, but it takes too long for the spirochete to grow. ........ Read more »

Molins CR, Ashton LV, Wormser GP, Hess AM, Delorey MJ, Mahapatra S, Schriefer ME, & Belisle JT. (2015) Development of a metabolic biosignature for detection of early Lyme disease. Clinical Infectious Diseases, 60(12), 1767-1775. PMID: 25761869  

  • December 30, 2014
  • 05:50 PM

Severe Lyme arthritis: Gagging on GAGs

by Microbe Fan in Spirochetes Unwound

Janis Weis' group has been mapping genetic variants that make laboratory mice prone to severe Lyme arthritis.  One of these variants is described in a paper that appeared in The Journal of Clinical Investigation earlier this year.  The affected gene encodes the enzyme β-glucuronidase, which carries out a critical function in the lysosome. β-glucuronidase cooperates with other degradative enzymes in the lysosome to break down glycosaminoglycans (GAGs) into their individual sugar units........ Read more »

Bramwell KK, Ma Y, Weis JH, Chen X, Zachary JF, Teuscher C, & Weis JJ. (2014) Lysosomal β-glucuronidase regulates Lyme and rheumatoid arthritis severity. The Journal of Clinical Investigation, 124(1), 311-320. PMID: 24334460  

Pancewicz S, Popko J, Rutkowski R, Knaś M, Grygorczuk S, Guszczyn T, Bruczko M, Szajda S, Zajkowska J, Kondrusik M.... (2009) Activity of lysosomal exoglycosidases in serum and synovial fluid in patients with chronic Lyme and rheumatoid arthritis. Scandinavian Journal of Infectious Diseases, 41(8), 584-589. PMID: 19513935  

Jiang D, Liang J, Fan J, Yu S, Chen S, Luo Y, Prestwich GD, Mascarenhas MM, Garg HG, Quinn DA.... (2005) Regulation of lung injury and repair by Toll-like receptors and hyaluronan. Nature Medicine, 11(11), 1173-1179. PMID: 16244651  

  • March 10, 2014
  • 01:55 PM

Video microscopy of ticks acquiring the Lyme disease spirochete from mice

by Microbe Fan in Spirochetes Unwound

The bite of an infected Ixodes hard tick transmits the Lyme disease spirochete, Borrelia burgdorferi, to humans.  Ticks acquire B. burgdorferi by feeding on reservoir hosts colonized with the spirochete.  Reservoir hosts include small mammals such as the white-footed mouse, the main reservoir of B. burgdorferi in the northeastern United States.A study that just came out in The Yale Journal of Biology and Medicine is accompanied by videos of Borrelia burgdorferi being transmitted betwee........ Read more »

Anderson JF, & Magnarelli LA. (2008) Biology of ticks. Infectious Disease Clinics of North America, 22(2), 195. PMID: 18452797  

  • December 13, 2013
  • 03:31 AM

Escape of the Lyme disease spirochete from the bloodstream involves multiple adhesins and receptors

by Microbe Fan in Spirochetes Unwound

Microbial pathogens that cause systemic infections often travel within the circulatory system to spread throughout the host.  Eventually, these pathogens exit from the bloodstream to get to their target organ.  The first step of exit, adherence to the inner surface of the vessel wall, is probably the most challenging one because the rapidly flowing blood shoots the microbes through the capillaries.  A recent review described the process akin to "a spider trying to gain a foothold ........ Read more »

  • October 15, 2013
  • 11:07 PM

Towards sterilizing immunity against Leptospira with a DNA vaccine

by Microbe Fan in Spirochetes Unwound

In my previous post, I described the failure of researchers to come up with a conventional protein-based subunit vaccine that confers sterilizing immunity against leptospirosis.  What I mean by "conventional" subunit vaccine is a mixture of purified recombinant Leptospira protein with an adjuvant (either aluminum hydroxide or Freund's).  Although an antibody response was detected against most proteins tested, immunization failed to prevent kidney colonization in every case, including t........ Read more »

  • September 15, 2013
  • 07:59 PM

Is sterilizing immunity against Leptospira possible with protein subunit vaccines?

by Microbe Fan in Spirochetes Unwound

With complete bacterial genome sequences now available, "reverse vaccinology" can be conducted to identify proteins that can function as subunit vaccines.  The "gene first" approach of reverse vaccinology relies upon computer analysis of the genome sequence to identify encoded proteins with  features common to known surface-exposed and secreted bacterial proteins.  The selected genes can then be cloned and expressed as recombinant proteins.  The proteins, which may number in ........ Read more »

  • March 13, 2013
  • 01:39 PM

Triggering OspC production in Borrelia burgdorferi during tick feeding: Is temperature the real signal?

by Microbe Fan in Spirochetes Unwound

The Ixodes tick, the vector of the Lyme disease spirochete, goes months without a meal.  During this time, the Borrelia burgdorferi spirochetes living in its midgut live quiet lives, sipping on the tick's antifreeze to sustain themselves. When the tick finally takes a blood meal from a warm-blooded victim, B. burgdorferi responds by producing a number of new proteins, some of which are needed for transmission to and infection of the mammalian host.  Among these proteins is the outer su........ Read more »

  • February 19, 2013
  • 01:50 PM

Is the major outer membrane lipoprotein LipL32 really exposed on the surface of Leptospira?

by Microbe Fan in Spirochetes Unwound

Here's a study that may come as a surprise to those in the leptospirosis field.  The outer membrane lipoprotein LipL32 is believed to be the dominant protein on the cell surface of pathogenic species of Leptospira.  However, according to a new PLoS One article written by Pinne and Haake at UCLA, LipL32 may not be present on the surface at all.  This is an important issue to get right because the function proposed for LipL32, attachment to the extracellular matrix during infection,........ Read more »

  • February 4, 2013
  • 04:18 PM

An autoantigen targeted during Lyme arthritis

by Microbe Fan in Spirochetes Unwound

Infection by the spirochete Borrelia burgdorferi, if left untreated, can lead to a form of Lyme disease called Lyme arthritis.  About 10% of Lyme arthritis patients end up with a chronic form that doesn't go away with antibiotic treatment.  Allen Steere's group has long suspected that the antibiotic-refractory form of Lyme arthritis involves an autoimmune process.  This notion seems reasonable since those with antibiotic-refractory Lyme arthritis tend to have certain forms of the ........ Read more »

  • January 14, 2013
  • 02:42 PM

LigB of Leptospira interrogans: Avoiding or exploiting complement?

by Microbe Fan in Spirochetes Unwound

LigB has turned out to be a versatile surface protein for Leptospira interrogans.  The protein is one of several that the spirochete uses to stick to the extracellular matrix, a critical step in colonizing host tissues.  In addition, LigB's ability to bind fibrinogen may help L. interrogans spread within the host by slowing clot formation.  According to separate studies from the U.S. and Brazil published last year, LigB also helps L. interrogans fend off attack by the host complem........ Read more »

  • January 1, 2013
  • 01:25 AM

Biofilms of the Lyme disease spirochete

by Microbe Fan in Spirochetes Unwound

Thanks to a recent study published in PLoS One, we now know that free-swimming Borrelia burgdorferi are able to organize themselves into a sedentary community called a biofilm.  This is not too surprising since most other bacteria are capable of the same feat when provided the opportunity.  In fact, outside of the laboratory many bacteria, including those that live on and within us, spend much of their time within biofilms.Prior to the 1990s biofilms were thought to be blobs of goo con........ Read more »

Sapi, E., Bastian, S.L., Mpoy, C.M., Scott, S., Rattelle, A., Pabbati, N., Poruri, A., Burugu, D., Theophilus, P.A.S., Pham, T.V.... (2012) Characterization of biofilm formation by Borrelia burgdorferi in vitro. PLoS ONE, 7(10). DOI: 10.1371/journal.pone.0048277  

  • November 26, 2012
  • 01:49 PM

A post-Thanksgiving story of leptospirosis

by Microbe Fan in Spirochetes Unwound

I'm about half way through 1491, a book that gives readers a view of the Americas before Columbus showed up.  It also describes the devastating impact that foreign infectious diseases had on the native population as Europeans explored the New World.One chapter tells the story of Tisquantum (Squanto), who lived in the village of Patuxet, one of the many Indian communities thriving along the coast of New England at the time.  In 1614 Thomas Hunt, a British slave trader, kidnapped Tisquan........ Read more »

  • November 8, 2012
  • 01:56 PM

Inflammatory spirochete debris left behind following antibiotic treatment for Lyme disease

by Microbe Fan in Spirochetes Unwound

According to the CDC, 10-20% of Lyme disease patients who have completed antibiotic therapy continue to suffer from symptoms such as joint, muscle, and neurological pain.  The following hypotheses are often presented as possible reasons for the lingering symptoms:  autoimmunity triggered by the infection, tissue damage inflicted by the spirochetes, and (depending on whom you ask) failure of antibiotics to kill all the spirochetes.  A new paper from Linda Bockenstedt's group at Yal........ Read more »

Bockenstedt, L., Gonzalez, D., Haberman, A., & Belperron, A. (2012) Spirochete antigens persist near cartilage after murine Lyme borreliosis therapy. Journal of Clinical Investigation, 122(7), 2652-2660. DOI: 10.1172/JCI58813  

  • July 12, 2012
  • 01:46 PM

Borrelia burgdorferi needs the alternative sigma factor RpoS to flee from the tick's midgut

by Microbe Fan in Spirochetes Unwound

The alternative sigma factor RpoS is a key player in the life cycle of Borrelia burgdorferi, the Lyme disease spirochete.  RpoS directs RNA polymerase to transcribe genes with promoters recognized by the alternative sigma factor.  B. burgdorferi deploys RpoS to directly or indirectly boost transcription of 103 out of its ~1400 genes while inside a mammalian host.  The most famous RpoS-dependent gene is ospC, which encodes a surface protein that enables B. burgdorferi to survive th........ Read more »

  • June 22, 2012
  • 01:54 PM

Looking for the syphilis spirochete in ancient bones

by Microbe Fan in Spirochetes Unwound

PCR is a powerful tool that has been used to detect microbial DNA in human remains unearthed by archaeologists.  This approach has helped reveal when and where infectious diseases such as tuberculosis and the plague have afflicted human populations in the past.  With the controversy raging over the question of whether the syphilis spirochete was present in Europe before Columbus sailed to America, one would think that scientists would have applied this technique to detect Treponema pal........ Read more »

  • May 28, 2012
  • 04:53 AM

Do nonspiral spirochetes help clean our environment?

by Microbe Fan in Spirochetes Unwound

Members of the spirochete phylum Spirochaetes are recognized easily by their long spiral shape, which allows their periplasmic flagella to power them through viscous environments.  But scientists are discovering that not all spirochetes share this peculiar shape.  Two bacterial isolates recovered from freshwater sediments in Michigan were spherical and lacked flagella, yet phylogenetic analysis of their 16S rRNA and other genes placed them firmly within Spirochaetes.  The genus Sp........ Read more »

Ritalahti, K.M., Justicia-Leon, S.D., Cusick, K.D., Ramos-Hernandez, N., Rubin, M., Dornbush, J., & Loffler, F.E. (2011) Sphaerochaeta globosa gen. nov., sp. nov. and Sphaerochaeta pleomorpha sp. nov., free-living, spherical spirochaetes. INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY, 62(1), 210-216. DOI: 10.1099/ijs.0.023986-0  

Franzmann P.D., & Dobson S.J. (1992) Cell wall-less, free-living spirochetes in Antarctica. FEMS microbiology letters, 76(3), 289-292. PMID: 1385265  

  • May 13, 2012
  • 12:39 PM

A tick protein helps Lyme disease spirochetes fight complement

by Microbe Fan in Spirochetes Unwound

Microbial pathogens attempting to establish an infection face the daunting challenge of overcoming the complement system.  To survive the onslaught of complement proteins, pathogenic microbes express surface structures that resist or manipulate the action of complement.  Not surprisingly, many Lyme disease Borrelia strains express proteins ("CRASPs" and "Erps") that ward off complement.  But they also get help from a protein found in the saliva of the Ixodes tick, according to a s........ Read more »

  • February 27, 2012
  • 01:47 PM

The magic of antibiotic tolerance

by Microbe Fan in Spirochetes Unwound

Bactericidal antibiotics are effective at killing proliferating bacteria as long as they don't carry mutated or acquired genes that encode resistance to the antibiotics. Unfortunately even antibiotic-sensitive bacteria can tolerate antibiotics under some circumstances. Bacteria that are in a nondividing "dormant" state often survive antibiotic exposure.  When the antibiotic is removed and growth resumes, the bacteria regain susceptibility to antibiotics.At first glance antibiotic tolerance........ Read more »

Nguyen, D., Joshi-Datar, A., Lepine, F., Bauerle, E., Olakanmi, O., Beer, K., McKay, G., Siehnel, R., Schafhauser, J., Wang, Y.... (2011) Active starvation responses mediate antibiotic tolerance in biofilms and nutrient-limited bacteria. Science, 334(6058), 982-986. DOI: 10.1126/science.1211037  

Kohanski, M.A., Dwyer, D.J., Hayete, B., Lawrence, C.A., & Collins, J.J. (2007) A common mechanism of cellular death induced by bactericidal antibiotics. Cell, 130(5), 797-810. DOI: 10.1016/j.cell.2007.06.049  

Lewis, K. (2010) Persister cells. Annual Review of Microbiology, 64(1), 357-372. DOI: 10.1146/annurev.micro.112408.134306  

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