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Spirochetes Unwound
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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 »
Jutras, B.L., Chenail, A.M., & Stevenson, B. (2012) Changes in bacterial growth rate govern expression of the Borrelia burgdorferi OspC and Erp infection-associated surface proteins. Journal of Bacteriology, 195(4), 757-764. DOI: 10.1128/JB.01956-12
Schwan, T.G., Piesman, J., Golde, W.T., Dolan, M.C., & Rosa, P.A. (1995) Induction of an outer surface protein on Borrelia burgdorferi during tick feeding. Proceedings of the National Academy of Sciences, 92(7), 2909-2913. DOI: 10.1073/pnas.92.7.2909
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 »
Pinne, M., & Haake, D.A. (2013) LipL32 is a subsurface lipoprotein of Leptospira interrogans: Presentation of new data and reevaluation of previous studies. PLoS ONE, 8(1). DOI: 10.1371/journal.pone.0051025
Cullen, P.A., Xu, X., Matsunaga, J., Sanchez, Y., Ko, A.I., Haake, D.A., & Adler, B. (2005) Surfaceome of Leptospira spp. Infection and Immunity, 73(8), 4853-4863. DOI: 10.1128/IAI.73.8.4853-4863.2005
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 »
Drouin, E.E., Seward, R.J., Strle, K., McHugh, G., Katchar, K., Londoño, D., Yao, C., Costello, C.E., & Steere, A.C. (2013) A novel human autoantigen, endothelial cell growth factor, is a target of T and B cell responses in patients with Lyme disease. Arthritis , 65(1), 186-196. DOI: 10.1002/art.37732
Seward, R.J., Drouin, E.E., Steere, A.C., & Costello, C.E. (2010) Peptides presented by HLA-DR molecules in synovia of patients with rheumatoid arthritis or antibiotic-refractory Lyme arthritis. Molecular , 10(3). DOI: 10.1074/mcp.M110.002477
Steere, A.C., Drouin, E.E., & Glickstein, L.J. (2011) Relationship between immunity to Borrelia burgdorferi Outer-surface protein A (OspA) and Lyme arthritis. Clinical Infectious Diseases, 52(Supplement 3). DOI: 10.1093/cid/ciq117
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 »
Castiblanco-Valencia MM, Fraga TR, da Silva LB, Monaris D, Abreu PAE, Strobel S, Jozsi M, Isaac L, & Barbosa AS. (2012) Leptospiral immunoglobulin-like proteins interact with human complement regulators factor H, FHL-1, FHR-1, and C4BP. Journal of Infectious Diseases, 205(6), 995-1004. DOI: 10.1093/infdis/jir875
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
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 »
Marr John S., & Cathey John T. (2010) New hypothesis for cause of epidemic among Native Americans, New England, 1616–1619. Emerging Infectious Diseases, 16(2), 281-286. DOI: 10.3201/eid1602.090276
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
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 »
Dunham-Ems SM, Caimano MJ, Eggers CH, & Radolf JD. (2012) Borrelia burgdorferi requires the alternative sigma factor RpoS for dissemination within the vector during tick-to-mammal transmission. PLoS pathogens, 8(2). PMID: 22359504
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 »
Montiel R, Solórzano E, Díaz N, Álvarez-Sandoval BA, González-Ruiz M, Cañadas MP, Simões N, Isidro A, & Malgosa A. (2012) Neonate human remains: a window of opportunity to the molecular study of ancient syphilis. PloS one, 7(5). PMID: 22567153
Bouwman, AS, & Brown, TA. (2005) The limits of biomolecular palaeopahology: ancient DNA cannot be used to study venereal syphilis. Journal of Archaeological Science, 703-713. DOI: 10.1016/j.jas.2004.11.014
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 »
Caro-Quintero, A., Ritalahti, K.M., Cusick, K.D., Loffler, F.E., & Konstantinidis, K.T. (2012) The chimeric genome of Sphaerochaeta: Nonspiral spirochetes that break with the prevalent dogma in spirochete biology. mBio, 3(3). DOI: 10.1128/mBio.00025-12
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
Alban P.S., Johnson P.W., & Nelson D.R. (2000) Serum-starvation-induced changes in protein synthesis and morphology of Borrelia burgdorferi. Microbiology (Reading, England), 119-127. PMID: 10658658
Franzmann P.D., & Dobson S.J. (1992) Cell wall-less, free-living spirochetes in Antarctica. FEMS microbiology letters, 76(3), 289-292. PMID: 1385265
Dröge S., Fröhlich J., Radek R., & König H. (2006) Spirochaeta coccoides sp. nov., a novel coccoid spirochete from the hindgut of the termite Neotermes castaneus. Applied and environmental microbiology, 72(1), 392-397. PMID: 16391069
Abt, B., Han, C., Scheuner, C., Lu, M., Lapidus, A., Nolan, M., Lucas, S., Hammon, N., Deshpande, S., Cheng, J.... (2012) Complete genome sequence of the termite hindgut bacterium Spirochaeta coccoides type strain (SPN1T), reclassification in the genus Sphaerochaeta as Sphaerochaeta coccoides comb. nov. and emendations of the family Spirochaetaceae and the genus Sphaerochaet. Standards in Genomic Sciences, 6(2), 194-209. DOI: 10.4056/sigs.2796069
Taş, N., van Eekert, M.H.A., de Vos, W.M., & Smidt, H. (2009) The little bacteria that can - diversity, genomics and ecophysiology of ‘Dehalococcoides’ spp. in contaminated environments. Microbial Biotechnology, 3(4), 389-402. DOI: 10.1111/j.1751-7915.2009.00147.x
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 »
Schuijt, T.J., Coumou, J., Narasimhan, S., Dai, J., DePonte, K., Wouters, D., Brouwer, M., Oei, A., Roelofs, J.J.T.H., van Dam, A.P.... (2011) A tick mannose-binding lectin inhibitor interferes with the vertebrate complement cascade to enhance transmission of the Lyme disease agent. Cell Host , 10(2), 136-146. DOI: 10.1016/j.chom.2011.06.010
Marconi, R.T., & McDowell, J.V. (2011) Tick salivary proteins offer the Lyme disease spirochetes an easy ride and another way to hide. Cell Host , 10(2), 95-96. DOI: 10.1016/j.chom.2011.08.003
Schuijt, T.J., Narasimhan, S., Daffre, S., DePonte, K., Hovius, J.W.R., Veer, C., van der Poll, T., Bakhtiari, K., Meijers, J.C.M., Boder, E.T.... (2011) Identification and characterization of Ixodes scapularis antigens that elicit tick immunity using yeast surface display. PLoS ONE, 6(1). DOI: 10.1371/journal.pone.0015926
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
Bigger, J.W. (1944) Treatment of staphylococcal infections with penicillin by intermittent sterilisation. The Lancet, 244(6320), 497-500. DOI: 10.1016/S0140-6736(00)74210-3
Moyed H.S., & Bertrand K.P. (1983) hipA, a newly recognized gene of Escherichia coli K-12 that affects frequency of persistence after inhibition of murein synthesis. Journal of bacteriology, 155(2), 768-775. PMID: 6348026
Cashel, M., & Gallant, J. (1969) Two compounds implicated in the function of the RC gene of Escherichia coli. Nature, 221(5183), 838-841. DOI: 10.1038/221838a0
Paul, B., Barker, M.M., Ross, W., Schneider, D.A., Webb, C., Foster, J.W., & Gourse, R.L. (2004) DksA: a critical component of the transcription initiation machinery that potentiates the regulation of rRNA promoters by ppGpp and the initiating NTP. Cell, 118(3), 311-322. DOI: 10.1016/j.cell.2004.07.009
Korch, S.B., Henderson, T.A., & Hill, T.M. (2003) Characterization of the hipA7 allele of Escherichia coli and evidence that high persistence is governed by (p)ppGpp synthesis. Molecular Microbiology, 50(4), 1199-1213. DOI: 10.1046/j.1365-2958.2003.03779.x
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
by Microbe Fan in Spirochetes Unwound
The first recorded syphilis epidemic flared up in war-torn Naples in 1494, only two years after Columbus discovered the New World. From there syphilis spread throughout Europe. Ever since then, controversy has raged about the origin of syphilis. A popular belief is that Columbus's crew got infected in the New World and brought the spirochete back to Europe, where they transmitted the disease to others while serving as mercenaries during the first Italian War. The competin........ Read more »
Harper, K.N., Zuckerman, M.K., Harper, M.L., Kingston, J.D., & Armelagos, G.J. (2011) The origin and antiquity of syphilis revisited: an appraisal of Old World pre-Columbian evidence for treponemal infection. American Journal of Physical Anthropology, 146(S53), 99-133. DOI: 10.1002/ajpa.21613
von Hunnius, T.E., Roberts, C.A., Boylston, A., & Saunders, S.R. (2006) Histological identification of syphilis in pre-Columbian England. American Journal of Physical Anthropology, 129(4), 559-566. DOI: 10.1002/ajpa.20335
by Microbe Fan in Spirochetes Unwound
Feeding Ixodes ticks harboring Borrelia burgdorferi deposit the Lyme disease spirochete in the skin of the victim. The spirochetes remain in the skin for a few days before entering the bloodstream to spread throughout the host. The delay in dissemination provides a window of opportunity to stop the infection by simply applying antibiotics to the skin where the tick was feeding. Topical application of antibiotics would allow patients to avoid experiencing side effects associated........ Read more »
Shih, C.-M., & Spielman, A. (1993) Topical prophylaxis for Lyme disease after tick bite in a rodent model. Journal of Infectious Diseases, 168(4), 1042-1045. DOI: 10.1093/infdis/168.4.1042
Wormser, G.P., Daniels, T.J., Bittker, S., Cooper, D., Wang, G., & Pavia, C.S. (2011) Failure of topical antibiotics to prevent disseminated Borrelia burgdorferi infection following a tick bite in C3H/HeJ mice. Journal of Infectious Diseases. DOI: 10.1093/infdis/jir382
Knauer, J., Krupka, I., Fueldner, C., Lehmann, J., & Straubinger, R.K. (2011) Evaluation of the preventive capacities of a topically applied azithromycin formulation against Lyme borreliosis in a murine model. Journal of Antimicrobial Chemotherapy. DOI: 10.1093/jac/dkr371
by Microbe Fan in Spirochetes Unwound
In the northeastern United States the Lyme disease spirochete Borrelia burgdorferi spreads from one white-footed mouse to another by hitching a ride in the tick Ixodes scapularis. Transmission between tick and mouse occurs during the tick's rare blood meals. The larval tick acquires B. burgdorferi from an infected mouse during a blood meal late in the summer, and the spirochetes take up shelter in the tick's midgut. Later the larva molts into a nymph, which then completes the transmi........ Read more »
Pappas, C.J., Iyer, R., Petzke, M.M., Caimano, M.J., Radolf, J.D., & Schwartz, I. (2011) Borrelia burgdorferi requires glycerol for maximum fitness during the tick phase of the enzootic cycle. PLoS Pathogens, 7(7). DOI: 10.1371/journal.ppat.1002102
by Microbe Fan in Spirochetes Unwound
Two recent papers tested the effectiveness of topical antibiotics in preventing Borrelia burgdorferi infection in mice following a tick bite. Infection by the Lyme disease spirochete was successfully halted in the Knauer et al. study from Germany1 but not in the Wormser et al. study conducted in New York.2 However a flaw in the Knauer study may have unfairly tipped the outcome in the antbiotic's favor. (I'll save the Wormser study for another post.)The paper by Knauer and colle........ Read more »
Knauer, J., Krupka, I., Fueldner, C., Lehmann, J., & Straubinger, R. (2011) Evaluation of the preventive capacities of a topically applied azithromycin formulation against Lyme borreliosis in a murine model. Journal of Antimicrobial Chemotherapy. DOI: 10.1093/jac/dkr371
Wormser, G., Daniels, T., Bittker, S., Cooper, D., Wang, G., & Pavia, C. (2011) Failure of topical antibiotics to prevent disseminated Borrelia burgdorferi infection following a tick bite in C3H/HeJ mice. Journal of Infectious Diseases. DOI: 10.1093/infdis/jir382
by Microbe Fan in Spirochetes Unwound
For the first time scientists have shown that Toll-like receptor 8 (TLR8), a microbial RNA sensor located inside phagocytes, detects what is primarily an extracellular pathogen, the Lyme disease spirochete Borrelia burgdorferi.1 As one may expect, the phagocytes secreted a mixture of inflammatory cytokines in response to the spirochete. But they also expressed at least one of the type I interferons (IFNs), which until recent years were thought to be produced only in response to viral........ Read more »
Cervantes, J.L., Dunham-Ems, S.M., La Vake, C.J., Petzke, M.M., Sahay, B., Sellati, T.J., Radolf, J.D., & Salazar, J.C. (2011) Phagosomal signaling by Borrelia burgdorferi in human monocytes involves Toll-like receptor (TLR) 2 and TLR8 cooperativity and TLR8-mediated induction of IFN-β. Proceedings of the National Academy of Sciences, 108(9), 3683-3688. DOI: 10.1073/pnas.1013776108
Mancuso G, Midiri A, Biondo C, Beninati C, Zummo S, Galbo R, Tomasello F, Gambuzza M, Macrì G, Ruggeri A.... (2007) Type I IFN signaling is crucial for host resistance against different species of pathogenic bacteria. Journal of Immunology, 178(5), 3126-3133. PMID: 17312160
Kawai, T., & Akira, S. (2010) The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nature Immunology, 11(5), 373-384. DOI: 10.1038/ni.1863
Salazar, J.C., Duhnam-Ems, S., La Vake, C., Cruz, A.R., Moore, M.W., Caimano, M.J., Velez-Climent, L., Shupe, J., Krueger, W., & Radolf, J.D. (2009) Activation of human monocytes by live Borrelia burgdorferi generates TLR2-dependent and -independent responses which include induction of IFN-β. PLoS Pathogens, 5(5). DOI: 10.1371/journal.ppat.1000444
Miller JC, Ma Y, Bian J, Sheehan KC, Zachary JF, Weis JH, Schreiber RD, & Weis JJ. (2008) A critical role for type I IFN in arthritis development following Borrelia burgdorferi infection of mice. Journal of Immunology, 181(12), 8492-8503. PMID: 19050267
by Microbe Fan in Spirochetes Unwound
Conventional vaccines target the surface components or secreted toxins of pathogens. Erol Fikrig's group at Yale University has been exploring an unconventional approach towards developing a vaccine for Lyme disease, which is caused by a tick-borne pathogen. Their recent work, published in the November issue of PLoS Pathogens, demonstrated partial success in protecting laboratory mice by immunization with a protein found in the saliva of the Ixodes tick vector.Ixodes ticks spend seve........ Read more »
Dai, J., Narasimhan, S., Zhang, L., Liu, L., Wang, P., & Fikrig, E. (2010) Tick histamine release factor is critical for Ixodes scapularis engorgement and transmission of the Lyme disease agent. PLoS Pathogens, 6(11). DOI: 10.1371/journal.ppat.1001205
Dai, J., Wang, P., Adusumilli, S., Booth, C.J., Narasimhan, S., Anguita, J., & Fikrig, E. (2009) Antibodies against a tick protein, Salp15, protect mice from the Lyme disease agent. Cell Host , 6(5), 482-492. DOI: 10.1016/j.chom.2009.10.006
by Microbe Fan in Spirochetes Unwound
Bacterial lipoproteins are proteins with covalently-attached lipid molecules that anchor the protein to the cytoplasmic or outer membrane. The lipid molecules are attached to the cysteine located at the amino terminus of the lipoprotein. The lipoprotein's protein component, being hydrophilic (water-loving), sticks out from the membrane. Different bacterial lipoproteins participate in a variety of functions, including transport of molecules, stabilization of the cell wall, signal tran........ Read more »
TOKUDA, H. (2009) Biogenesis of outer membranes in Gram-negative bacteria. Bioscience, Biotechnology, and Biochemistry, 73(3), 465-473. DOI: 10.1271/bbb.80778
TOKUDA, H. (2004) Sorting of lipoproteins to the outer membrane in E. coli. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1693(1), 5-13. DOI: 10.1016/j.bbamcr.2004.02.005
Schulze, R., & Zückert, W. (2006) Borrelia burgdorferi lipoproteins are secreted to the outer surface by default. Molecular Microbiology, 59(5), 1473-1484. DOI: 10.1111/j.1365-2958.2006.05039.x
by Microbe Fan in Spirochetes Unwound
The spirochete Borrelia burgdorferi is the tick-borne agent of Lyme disease, which affects the joints, nervous system, and heart. After being deposited into the skin by an infected tick, the spirochete must enter the bloodstream so that it can circulate in the blood to gain access to its target organs.The host doesn't sit idly as B. burgdorferi establishes an infection. Invariant natural killer (iNKT) cells are one of the tools deployed by the immune system in its battle agains........ Read more »
Lee, W.Y., Moriarty, T.J., Wong, C.H.Y., Zhou, H., Strieter, R.M., van Rooijen, N., Chaconas, G., & Kubes, P. (2010) An intravascular immune response to Borrelia burgdorferi involves Kupffer cells and iNKT cells. Nature Immunology, 11(4), 295-302. DOI: 10.1038/ni.1855
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