Pleomorphic Variants of Borreliella (syn. Borrelia) burgdorferi Express Evolutionary Distinct Transcriptomes.

Borreliella (syn. Borrelia) burgdorferi is a spirochete bacterium that causes tick-borne Lyme disease. Along its lifecycle B. burgdorferi develops several pleomorphic forms with unclear biological and medical relevance. Surprisingly, these morphotypes have never been compared at the global transcriptome level. To fill this void, we grew B. burgdorferi spirochete, round body, bleb, and biofilm-dominated cultures and recovered their transcriptomes by RNAseq profiling. We found that round bodies share similar expression profiles with spirochetes, despite their morphological differences. This sharply contrasts to blebs and biofilms that showed unique transcriptomes, profoundly distinct from spirochetes and round bodies. To better characterize differentially expressed genes in non-spirochete morphotypes, we performed functional, positional, and evolutionary enrichment analyses. Our results suggest that spirochete to round body transition relies on the delicate regulation of a relatively small number of highly conserved genes, which are located on the main chromosome and involved in translation. In contrast, spirochete to bleb or biofilm transition includes substantial reshaping of transcription profiles towards plasmids-residing and evolutionary young genes, which originated in the ancestor of Borreliaceae. Despite their abundance the function of these Borreliaceae-specific genes is largely unknown. However, many known Lyme disease virulence genes implicated in immune evasion and tissue adhesion originated in this evolutionary period. Taken together, these regularities point to the possibility that bleb and biofilm morphotypes might be important in the dissemination and persistence of B. burgdorferi inside the mammalian host. On the other hand, they prioritize the large pool of unstudied Borreliaceae-specific genes for functional characterization because this subset likely contains undiscovered Lyme disease pathogenesis genes.

Classification and Staging of Morgellons Disease: Lessons from Syphilis.

INTRODUCTION: Morgellons disease (MD) is a contested dermopathy that is associated with Borrelia spirochetal infection. A simple classification system was previously established to help validate the disease based on clinical features (classes I-IV). METHODS: Drawing on historical and pathological parallels with syphilis, we formulated a more detailed staging system based on clinical features as well as severity of skin lesions and corresponding histopathological infection patterns, as determined by anti-Borrelia immunohistochemical staining. RESULTS: Clinical classes I-IV of MD are further categorized as mild, moderate and severe, or stages A, B and C, respectively, based on histopathological findings. Stage A lesions demonstrated little or no immune infiltrates and little or no disorganization of cells; macrophages were not present, and hemorrhage was negligible. Extracellular isolated spirochetes and intracellular staining of keratinocytes in the lower epidermis was occasionally seen. Stage C lesions demonstrated positive staining of keratinocytes in the stratum basale and stratum spinosum and positive intracellular staining of macrophages for Borrelia. Aggregate Borrelia colonies were frequently encountered, hemorrhage was frequent, and intracellularly stained fibroblasts were occasionally seen. Stage B lesions demonstrated a pattern intermediate between Stages A and C. CONCLUSION: The enhanced staging system provides objective criteria to assess the severity of dermopathy in MD. Further studies are needed to determine the optimal treatment for MD based on this staging system related to Borrelia infection.

Seropositivity to Midichloria mitochondrii (order Rickettsiales) as a marker to determine the exposure of humans to tick bite.

Ixodes ricinus is the most common tick species parasitizing humans in Europe, and the main vector of Borrelia burgdorferi sensu lato, the causative agent of Lyme disease in the continent. This tick species also harbors the endosymbiont Midichloria mitochondrii, and there is strong evidence that this bacterium is inoculated into the vertebrate host during the blood meal. A high proportion of tick bites remains unnoticed due to rarity of immediate symptoms, implying the risk of occult tick-borne infections in turn a potential risk factor for the onset of chronic-degenerative diseases. Since suitable tools to determine the previous exposure to I. ricinus bites are needed, this work investigated whether seropositivity toward a protein of M. mitochondrii (rFliD) could represent a marker for diagnosis of I. ricinus bite. We screened 274 sera collected from patients from several European countries, at different risk of tick bite, using an ELISA protocol. Our results show a clear trend indicating that positivity to rFliD is higher where the tick bite can be regarded as certain/almost certain, and lower where there is an uncertainty on the bite, with the highest positivity in Lyme patients (47.30%) and the lowest (2.00%) in negative controls. According to the obtained results, M. mitochondrii can be regarded as a useful source of antigens, with the potential to be used to assess the exposure to ticks harboring this bacterium. In prospect, additional antigens from M. mitochondrii and tick salivary glands should be investigated and incorporated in a multi-antigen test for tick bite diagnosis.

First report of Borrelia miyamotoi in an Ixodes ricinus tick in Augsburg, Germany.

Borrelia miyamotoi, a spirochete found in the hard tick Ixodes ricinus, is thought to cause relapsing fever. The disease caused by this bacterium can manifest with high fever, fatigue and other symptoms. It may also lead to central nervous system involvement with symptoms similar to meningoencephalitis. DNA from ticks from the greater Augsburg region in Germany was subjected to qPCR for Borrelia spp., followed by nested PCR and subsequent sequencing for species identification of the qPCR positive samples. From 112 ticks, 20 were found to be positive for Borrelia. The DNA sequenced showed 50% Borrelia afzelli, 15% Borrelia garinii, 5% Borrelia valaisiana and one sequence was identified as Borrelia miyamotoi. The positive identification of Borrelia miyamotoi is unlikely to be due to contamination. In conclusion, Borrelia miyamotoi has been found in a tick in the Augsburg region for the first time. This follows on from previous reports of a low incidence of this bacterium in southern Germany around Lake Constance and in the Munich region. This infectious agent should be taken into account when patients present with recurring fever or neurological symptoms which cannot be otherwise explained. Tick-borne relapsing fever should now be considered as a cause of such symptoms and medical professionals should contemplate differential Borrelia testing when presented with corresponding symptoms.