Frontiers | Selective Essential Oils from Spice or Culinary Herbs Have High Activity against Stationary Phase and Biofilm Borrelia burgdorferi | Medicine

 Although the majority of patients with acute Lyme disease can be cured with the standard 2–4 week antibiotic treatment, about 10–20% of patients continue suffering from chronic symptoms described as posttreatment Lyme disease syndrome. While the cause for this is debated, one possibility is that persister bacteria are not killed by the current Lyme antibiotics and remain active in the system. It has been reported that essential oils have antimicrobial activities and some have been used by patients with persisting Lyme disease symptoms. However, the activity of essential oils against the causative agent Borrelia burgdorferi (B. burgdorferi) has not been well studied. Here, we evaluated the activity of 34 essential oils against B. burgdorferi stationary phase culture as a model for persister bacteria. We found that not all essential oils had activity against the B. burgdorferi stationary phase culture, with top five essential oils (oregano, cinnamon bark, clove bud, citronella, and wintergreen) at a low concentration of 0.25% showing high anti-persister activity that is more active than the known persister drug daptomycin. Interestingly, some highly active essential oils were found to have excellent anti-biofilm ability as shown by their ability to dissolve the aggregated biofilm-like structures. The top three hits, oregano, cinnamon bark, and clove bud completely eradicated all viable cells without any regrowth in subculture in fresh medium, whereas but not citronella and wintergreen did not have this effect. Carvacrol was found to be the most active ingredient of oregano oil showing excellent activity against B. burgdorferi stationary phase cells, while other ingredients of oregano oil p-cymene and α-terpinene had no apparent activity. Future studies are needed to characterize and optimize the active essential oils in drug combination studies in vitro and in vivo and to address their safety and pharmacokinetic properties before they can be considered as a novel treatment of persistent Lyme disease."



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Bacterial Amyloid and DNA are Important Constituents of Senile Plaques: Further Evidence of the Spirochetal and Biofilm Nature of Senile Plaques.

It has long been known that spirochetes form clumps or micro colonies in vitro and in vivo. Cortical spirochetal colonies in syphilitic dementia were considered as reproductive centers for spirochetes. Historic and recent data demonstrate that senile plaques in Alzheimer's disease (AD) are made up by spirochetes. Spirochetes, including Borrelia burgdorferi, are able to form biofilm in vitro. Senile plaques are also reported to contain elements of biofilm constituents. We expected that AβPP and Aβ (the main components of senile plaques) also occur in pure spirochetal biofilms, and bacterial DNA (an important component of biofilm) is also present in senile plaques. Histochemical, immunohistochemical, and in situ hybridization techniques and the TUNEL assay were used to answer these questions. The results obtained demonstrate that Aβ and DNA are key components of both pure spirochetal biofilms and senile plaques in AD and confirm the biofilm nature of senile plaques. These observations validate previous observations that AβPP and/or an AβPP-like amyloidogenic protein are an integral part of spirochetes, and indicate that bacterial amyloid is a constituent of senile plaques. DNA fragmentation in senile plaques further confirms their bacterial nature and provides biochemical evidence for spirochetal cell death. Spirochetes evade host defenses, locate intracellularly, form more resistant atypical forms and notably biofilms, which contribute to and sustain chronic infection and inflammation and explain the slowly progressive course of dementia in AD. To consider co-infecting microorganisms is equally important, as multi-species biofilms may result in a higher resistance to treatments and a more severe dementia.

New species of bacteria found to cause Lyme disease | Science News

Until recently, only one bacterium in North America was known to cause the disease: Borrelia burgdorferi. (In Europe, two other species are more common.)This year, researchers at Mayo Clinic testing blood and synovial fluid samples from people infected with Lyme disease discovered six infections that did not trace to B. burgdorferi. In addition to a rash, fever and other classic Lyme symptoms, those patients also experienced confusion, nausea and vomiting. “Not so typical for Lyme disease,” Mead observed.

A previously unknown species of Borrelia was causing the disease, the Mayo team reported in the May issue of Lancet Infectious Diseases. Infections from the newly named Borrelia mayoniiappear to cause unusually high concentrations of bacteria in the blood. The patients recovered after receiving the same antibiotics that treat Lyme disease. As of now, samples taken from ticks show that B. mayonii is only found in the Upper Midwest.

Bacterial Amyloid and DNA are Important Constituents of Senile Plaques: Further Evidence of the Spirochetal and Biofilm Nature of Senile Plaques

 It has long been known that spirochetes form clumps or micro colonies in vitro and in vivo. Cortical spirochetal colonies in syphilitic dementia were considered as reproductive centers for spirochetes. Historic and recent data demonstrate that senile plaques in Alzheimer’s disease (AD) are made up by spirochetes. Spirochetes, including Borrelia burgdorferi, are able to form biofilm in vitro. Senile plaques are also reported to contain elements of biofilm constituents. We expected that AβPP and Aβ (the main components of senile plaques) also occur in pure spirochetal biofilms, and bacterial DNA (an important component of biofilm) is also present in senile plaques. Histochemical, immunohistochemical, and in situ hybridization techniques and the TUNEL assay were used to answer these questions. The results obtained demonstrate that Aβ and DNA are key components of both pure spirochetal biofilms and senile plaques in AD and confirm the biofilm nature of senile plaques. These observations validate previous observations that AβPP and/or an AβPP-like amyloidogenic protein are an integral part of spirochetes, and indicate that bacterial amyloid is a constituent of senile plaques. DNA fragmentation in senile plaques further confirms their bacterial nature and provides biochemical evidence for spirochetal cell death. Spirochetes evade host defenses, locate intracellularly, form more resistant atypical forms and notably biofilms, which contribute to and sustain chronic infection and inflammation and explain the slowly progressive course of dementia in AD. To consider co-infecting microorganisms is equally important, as multi-species biofilms may result in a higher resistance to treatments and a more severe dementia.

Biofilms Alive in Alzheimer's Disease Plaques on Vimeo

Biofilms Alive in Alzheimer's Disease Plaques from Alan MacDonald on Vimeo.

Herpes Simplex Virus Type 1 and Other Pathogens are Key Causative Factors in Sporadic Alzheimer’s Disease - IOS Press

This review focuses on research in epidemiology, neuropathology, molecular biology, and genetics regarding the hypothesis that pathogens interact with susceptibility genes and are causative in sporadic Alzheimer’s disease (AD). Sporadic AD is a complex multifactorial neurodegenerative disease with evidence indicating coexisting multi-pathogen and inflammatory etiologies. There are significant associations between AD and various pathogens, including Herpes simplex virus type 1 (HSV-1), Cytomegalovirus, and other Herpesviridae, Chlamydophila pneumoniae, spirochetes, Helicobacter pylori, and various periodontal pathogens. These pathogens are able to evade destruction by the host immune system, leading to persistent infection. Bacterial and viral DNA and RNA and bacterial ligands increase the expression of pro-inflammatory molecules and activate the innate and adaptive immune systems. Evidence demonstrates that pathogens directly and indirectly induce AD pathology, including amyloid-β (Aβ) accumulation, phosphorylation of tau protein, neuronal injury, and apoptosis. Chronic brain infection with HSV-1, Chlamydophila pneumoniae, and spirochetes results in complex processes that interact to cause a vicious cycle of uncontrolled neuroinflammation and neurodegeneration. Infections such as Cytomegalovirus, Helicobacter pylori, and periodontal pathogens induce production of systemic pro-inflammatory cytokines that may cross the blood-brain barrier to promote neurodegeneration. Pathogen-induced inflammation and central nervous system accumulation of Aβ damages the blood-brain barrier, which contributes to the pathophysiology of AD. Apolipoprotein E4 (ApoE4) enhances brain infiltration by pathogens including HSV-1 and Chlamydophila pneumoniae. ApoE4 is also associated with an increased pro-inflammatory response by the immune system. Potential antimicrobial treatments for AD are discussed, including the rationale for antiviral and antibiotic clinical trials.

Suppression of Long-Lived Humoral Immunity Following Borrelia burgdorferi Infection

Lyme Disease caused by infection with Borrelia burgdorferi is an emerging infectious disease and already by far the most common vector-borne disease in the U.S. Similar to many other infections, infection with B. burgdorferi results in strong antibody response induction, which can be used clinically as a diagnostic measure of prior exposure. However, clinical studies have shown a sometimes-precipitous decline of such antibodies shortly following antibiotic treatment, revealing a potential deficit in the host’s ability to induce and/or maintain long-term protective antibodies. This is further supported by reports of frequent repeat infections with B. burgdorferi in endemic areas. The mechanisms underlying such a lack of long-term humoral immunity, however, remain unknown. We show here that B. burgdorferi infected mice show a similar rapid disappearance of Borrelia-specific antibodies after infection and subsequent antibiotic treatment. This failure was associated with development of only short-lived germinal centers, micro-anatomical locations from which long-lived immunity originates. These showed structural abnormalities and failed to induce memory B cells and long-lived plasma cells for months after the infection, rendering the mice susceptible to reinfection with the same strain of B. burgdorferi. The inability to induce long-lived immune responses was not due to the particular nature of the immunogenic antigens of B. burgdorferi, as antibodies to both T-dependent and T-independent Borrelia antigens lacked longevity and B cell memory induction. Furthermore, influenza immunization administered at the time of Borrelia infection also failed to induce robust antibody responses, dramatically reducing the protective antiviral capacity of the humoral response. Collectively, these studies show that B. burgdorferi-infection results in targeted and temporary immunosuppression of the host and bring new insight into the mechanisms underlying the failure to develop long-term immunity to this emerging disease threat."



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Researchers map neuroinflammation and nervous system manifestations of Lyme disease. | Healthinnovations

About 15% of patients with Lyme disease develop peripheral and central
nervous system involvement, often accompanied by debilitating and
painful symptoms. Now, researchers from Tulane National Primate Research
Center and Louisiana State University Health Sciences Center have
indicated that inflammation plays a causal role in the array of
neurologic changes associated with Lyme disease.  The team also showed
that the anti-inflammatory drug dexamethasone prevents many of these
reactions.

The researchers explain that Lyme disease in humans results from the bite of a tick infected with the spirochete Borrelia burgdorferi
(Bb). As Bb disseminates throughout the body, it can cause arthritis,
carditis, and neurologic deficits. When the nervous system is involved,
it is called Lyme neuroborreliosis (LNB).

Clinical symptoms of LNB of the
peripheral nervous system may include facial nerve palsy, neurogenic
pain radiating along the back into the legs and feet, limb pain, sensory
loss, or muscle weakness. Central nervous system involvement can
manifest as headache, fatigue, memory loss, learning disability,
depression, meningitis, and encephalopathy.  The results of the current
study suggest that inflammation has a causal role in the pathogenesis of
acute Lyme neuroborreliosis.

Borrelia burgdorferi/host interactome

A referenced  list of host genes and proteins involved in the spirochaete life cycle

Bacterial infection and Alzheimer's disease: a meta-analysis.

The possibility of an infectious etiology for Alzheimer's disease (AD) has been repeatedly postulated over the past three decades. We provide the first meta-analysis to address the relationship between bacterial infection and AD. Studies examining the association between AD and spirochetal bacteria or Chlamydophila pneumoniae (Cpn) were identified through a systematic search of the databases MEDLINE, EMBASE, PubMed, and Google Scholar. Data combined from 25 relevant, primarily case-control studies demonstrated a statistically significant association between AD and detectable evidence of infection of either bacterial group. We found over a ten-fold increased occurrence of AD when there is detectable evidence of spirochetal infection (OR: 10.61; 95% CI: 3.38-33.29) and over a four-fold increased occurrence of AD in a conservative risk estimate (OR: 4.45; 95% CI: 2.33-8.52). We found over a five-fold increased occurrence of AD with Cpn infection (OR: 5.66; 95% CI: 1.83-17.51). This study shows a strongly positive association between bacterial infection and AD. Further detailed investigation of the role of bacterial infection is warranted.

A study on the association between infectious burden and Alzheimer's disease.

BACKGROUND AND PURPOSE:

Previous studies suggested that the overall burden of prior infections contributes to cardiovascular
diseases and stroke. In the present study, the association between
infectious burden (IB) and Alzheimer's disease (AD) was examined.

METHODS:

Antibody titers to common infectious pathogens including cytomegalovirus (CMV),
herpes simplex virus type 1 (HSV-1), Borrelia burgdorferi, Chlamydophila
pneumoniae and Helicobacter pylori were measured by enzyme-linked
immunosorbent assay in 128 AD patients and 135 healthy controls. IB was
defined as a composite serological measure of exposure to these common
pathogens.

RESULTS:

Seropositivities toward zero-two, three and four-five of these pathogens were found in 44%, 40% and 16% of healthy controls but in 20%, 44% and 36% of AD patients, respectively. IB, bacterial burden and viral burden were independently associated with AD after adjusting for age, gender, education, APOE genotype and various comorbidities. Mini-Mental State Examination scores were negatively correlated with IB in all cases. Serum beta-amyloid protein (Aβ) levels (i.e. Aβ40, Aβ42 and total Aβ) and inflammatory cytokines (i.e. interferon-γ, tumor necrosis factor α, interleukin-1β and interleukin-6) in individuals exposed to four-five infectious pathogens were significantly higher than those exposed to zero-two or three pathogens.

CONCLUSIONS:

IB consisting of CMV, HSV-1, B. burgdorferi, C. pneumoniae and H. pylori is associated with AD. This study supports the role of infection/inflammation in the etiopathogenesis of AD.

New findings could help target the bacteria that cause Lyme disease and syphilis - Medical News Today

The bacterial pathogens that cause Lyme disease and syphilis are highly invasive. These pathogens, or spirochetes, can invade the central nervous system and, in the case of syphilis, enter the placenta, causing disease in the unborn child. In the Biophysical Journal, a Cell Press publication, researchers provide new insights into how these spirochetes penetrate tissue barriers. The findings might be used to develop new treatment strategies to help affected patients or even prevent infections.

Cerebrospinal fluid Alzheimer's biomarker profiles in CNS infections.

 The cerebrospinal fluid (CSF) biomarker profile in Alzheimer's disease (AD) is characterized by decreased beta amyloid (Aβ(1-42)), increased total and hyperphosphorylated tau (t-tau and p-tau, respectively), which is a useful diagnostic tool and gives insight in the pathogenesis of AD. It is of importance to study how these biomarkers react in other CNS diseases; therefore, we decided to analyse amyloid and tau biomarkers in different CNS infections. We also included analysis of soluble amyloid precursor proteins (sAPPα and -β). CSF Aβ(1-42), sAPPα and -β, t-tau and p-tau were analysed in bacterial meningitis (n = 12), Lyme neuroborreliosis (n = 13), herpes simplex virus type 1 (HSV-1) encephalitis (n = 10), HIV-associated dementia (HAD) (n = 21), AD (n = 21) and healthy controls (n = 42). Concurrent with AD, Aβ(1-42) was decreased in all groups except neuroborreliosis compared to controls. HSV-1 encephalitis, bacterial meningitis and HAD showed lower concentrations of sAPPα and -β compared to AD. T-tau was increased in AD and HSV-1 encephalitis compared to all other groups. P-tau was higher in AD and HSV-1 encephalitis compared to bacterial meningitis, HAD and control. Decreased CSF Aβ(1-42), sAPPα and -β in various CNS infections imply an effect of neuroinflammation on amyloid metabolism which is similar in regard to AD concerning Aβ(1-42), but differs concerning sAPPα and -β. These results clearly indicate different pathologic pathways in AD and infectious CNS disease and may provide help in the differential biomarker diagnostics. Increased p-tau in HSV-1 encephalitis probably reflect acute neuronal damage and necrosis.

CFS in Children and Adolescent: Ten Years of Retrospective Clinical Evaluation.

To estimate number of children being diagnosed with chronic fatigue syndrome (CFS). Methods. For a period of 10 years (2002-2011) data from children being referred for fatigue symptoms were collected retrospectively. Results. Thirty-seven children were referred. Four were excluded due to incorrect coding. Six (18%) patients received other diagnoses at the end of evaluation time. Of the 27 who received the diagnosis G93.3, four had a previous chronic illness, while 23 patients were previously healthy. All patients reported onset of fatigue symptom in relation to an infection, and all tested positive for IgG to either Epstein-Barr virus, cytomegalovirus or borrelia, indicating previous infection. There were 16 (59%) boys among the 27 patients. The mean age at the debut of fatigue symptoms was 141 months (SD 30) for boys and 136 months (SD 31) for girls, respectively. Being underweight, defined as BMI < 17.5, was found in 12 (44%) patients. Conclusion. An increasing number of children and adolescents are evaluated for CFS. The clinical assessment of children and adolescents with possible CFS need systematically evaluation. Nutritional status, possible eating disorder, and psychosocial issues need to be addressed and evaluated carefully. A multidisciplinary approach is essential when assessing CFS in children and adolescents. There is a need for European guidelines.

Classic microscopy reveals borrelia bacteria

Over the past year, two experienced biologists at Oslo University have seen something that very few scientists experience. They have been sought out by a persistent stream of people from all over Norway who are asking for help.
"People so sick that they can barely stand up have come here to Kristine Bonnevie Building at the University's Blindern campus. They are desperate, because they have not been diagnosed, and therefore have not received appropriate treatment.
Many of them suspect that they have developed chronic borreliosis following a tick bite, and that they have had the disease for a long time. But the tests used by the public health service do not detect it. They come to us with blood samples that they want us to test. They have heard rumours that we have developed a method that can give them answers", explain Ivar Mysterud and Morten Laane. The remarkable new method has just been published in the journal Biological and Biomedical Reports.

A simple method for the detection of live Borrelia spirochaetes in human blood using classical microscopy techniques Ivar Mysterud, Morten Motzfeldt Laane

Large-scale study of preventive antibiotic usage against Lyme disease

 "Today, at the start of the "Tick Week", the National Institute for Public Health and the Environment (RIVM) and Wageningen University are commencing a large-scale study to discover whether preventive use of antibiotics can stop Lyme disease developing after a tick bite. Of the more than 3400 ticks that were sent to RIVM via Tekenradar.nl (Tick radar) last year, more than 20% turned out to be infected with the Borrelia bacteria which can cause Lyme disease. Around 3% of the people bitten by ticks developed Lyme disease."

Increased IFNα activity and differential antibody response in patients with a history of Lyme disease and persistent cognitive deficits.

Following antibiotic treatment for Lyme disease, some patients report persistent or relapsing symptoms of pain, fatigue, and/or cognitive deficits. Factors other than active infection, including immune abnormalities, have been suggested, but few clues regarding mechanism have emerged. Furthermore, the effect of antibiotic treatment on immune response in affected individuals remains unknown. In this study, a longitudinal analysis of specific immune markers of interest was carried out in patients with a history of Lyme disease and persistent objective memory impairment, prior to and following treatment with either ceftriaxone or placebo. IFNα activity was measured by detection of serum-induced changes in specific target genes, using a functional cell-based assay and quantitative real-time PCR. Level and pattern of antibody reactivity to brain antigens and to Borrelia burgdorferi proteins were analyzed by ELISA and immunoblotting. Sera from the patient cohort induced significantly higher expression of IFIT1 and IFI44 target genes than those from healthy controls, indicating increased IFNα activity. Antibody reactivity to specific brain and borrelial proteins was significantly elevated in affected patients. IFNα activity and antibody profile did not change significantly in response to ceftriaxone. The heightened antibody response implies enhanced immune stimulation, possibly due to prolonged exposure to the organism prior to the initial diagnosis and antibiotic treatment of Lyme disease. The increase in IFNα activity is suggestive of a mechanism contributing to the ongoing neuropsychiatric symptoms.

Quirky Lyme disease bacteria: Unlike most organisms, they don't need iron, but crave manganese

 "Scientists have confirmed that the pathogen that causes Lyme Disease -- unlike any other known organism -- can exist without iron, a metal that all other life needs to make proteins and enzymes. Instead of iron, the bacteria substitute manganese to make an essential enzyme, thus eluding immune system defenses that protect the body by starving pathogens of iron."Borrelia burgdorferi requires unusually high levels of manganese, according to scientists at Johns Hopkins University (JHU), Woods Hole Oceanographic Institution (WHOI), and the University of Texas

Chronic or late lyme neuroborreliosis: analysis of evidence compared to chronic or late neurosyphilis.

Whether spirochetes persist in affected host tissues and cause the late/chronic manifestations of neurosyphilis was the subject of long-lasting debate. Detection of Treponema pallidum in the brains of patients with general paresis established a direct link between persisting infection and tertiary manifestations of neurosyphilis. Today, the same question is in the center of debate with respect to Lyme disease. The goal of this review was to compare the established pathological features of neurosyphilis with those available for Lyme neuroborreliosis. If the main tertiary forms of neurosyphilis also occur in Lyme neuroborreliosis and Borrelia burgdorferi can be detected in brain lesions would indicate that the spirochete is responsible for the neuropsychiatric manifestations of late/chronic Lyme neuroborreliosis. The substantial amounts of data available in the literature show that the major forms of late/chronic Lyme neuroborreliosis (meningovascular and meningoencephalitis) are clinically and pathologically confirmed. Borrelia burgdorferi was detected in association with tertiary brain lesions and cultivated from the affected brain or cerebrospinal fluid. The accumulated data also indicate that Borrelia burgdorferi is able to evade from destruction by the host immune reactions, persist in host tissues and sustain chronic infection and inflammation. These observations represent evidences that Borrelia burgdorferi in an analogous way to Treponema pallidum is responsible for the chronic/late manifestations of Lyme neuroborreliosis.Late Lyme neuroborreliosis is accepted by all existing guidelines in Europe, US and Canada. The terms chronic and late are synonymous and both define tertiary neurosyphilis or tertiary Lyme neuroborreliosis. The use of chronic and late Lyme neuroborreliosis as different entities is inaccurate and can be confusing. Further pathological investigations and the detection of spirochetes in infected tissues and body fluids are strongly needed.

Case study IDs Borrelia miyamotoi as cause of meningoencephalitis

The spirochete, Borrelia miyamotoi, may be an underrecognized cause of meningoencephalitis, according to a case study published in the Jan. 17 issue of the New England Journal of Medicine."