Cerebrospinal Fluid in a Small Cohort of Patients with Multiple Sclerosis Was Generally Free of Microbial DNA

Jovel, Juan; OʼKeefe, Sandra; Patterson, Jordan; Bording-Jorgensen, Michael; Wang, Weiwei; Mason, Andrew L.; Warren, Kenneth G.; Wong, Gane Ka‐Shu

doi:10.3389/fcimb.2016.00198

Cited by 12 publications

(11 citation statements)

References 58 publications

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“…In the former case, Veillonella parvula, a bacterium occasionally associated with meningitis was the predominant species, whilst Kocuria flava, apparently an environmental bacterium, predominated in the latter case. Thirty-four out of 43 samples contained <1% bacterial reads, which was regarded as a cross-or environmental contamination [83]. The involvement of bacteria, the relevance and the mechanisms of infection/inflammation to AD pathogenesis has been recently reviewed [84].…”

Section: Discussionmentioning

confidence: 99%

Rhamnolipids, Microbial Virulence Factors, in Alzheimer’s Disease

Andreadou

Pantazaki

Daniilidou

et al. 2017

JAD

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Abstract. Alzheimer's disease (AD) has been attributed to chronic bacterial infections. The recognition of human microbiota as a substantial contributor to health and disease is relatively recent and growing. During evolution, mammals live in a symbiotic state with myriads of microorganisms that survive at a diversity of tissue micro-surroundings. Microbes produce a plethora of secretory products [amyloids, lipopolysaccharides, virulence factors rhamnolipids (RLs), toxins, and a great number of neuroactive compounds]. The contribution of infectious microbial components to the pathophysiology of the human central nervous system including AD is considered potentially substantial, but the involvement of the RLs has never been reported. Here, RLs were isolated from serum and identified through various conventional methods including the colorimetric orcinol method, thin-layer chromatography, attenuated total reflection Fourier transform infrared (ATR-FTIR), and dot blot using antibodies against RLs. Dot blot demonstrated elevated RL levels in sera of AD patients compared to controls (p = 0.014). Moreover, ELISA showed similarly elevated RL levels in cerebrospinal fluid of both AD (0.188 versus 0.080) (p = 0.04) and mild cognitive impairment (0.188 versus 0.129) (p = 0.088) patients compared to healthy, and are wellcorrelated with the AD stages severity assessed using the Mini-Mental State Examination. These results provide conclusive evidence for the newly-reported implication of RLs in AD, adding it to the list of bacterial components, opening new avenues for AD investigation. Moreover, they strengthen and vindicate the divergence of research toward the exploration of bacterial involvement in AD generation and progression.

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Section: Discussionmentioning

confidence: 99%

Rhamnolipids, Microbial Virulence Factors, in Alzheimer’s Disease

Andreadou

Pantazaki

Daniilidou

et al. 2017

JAD

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“…Similarly, metagenomic analyses of cerebrospinal fluid (CSF) from MS patients reveal that the presence of Malassezia, Ascomycota, Funneliformis, Glomus, Cladosporium, Candida and Alternaria, however as concluded by these works, likely reflects environmental contaminants [191]. In contrast, Jovel et al using CSF from MS patients did not report any detection of fungal reads [192]. In Alzheimer's disease, fungal cells are detected in neurons through immunohistochemistry and confocal microscopy within brain tissue and these fungal species are further identified by nested PCR, where Candida, Cladosporium, Malassezia, Neosartorya, Phoma and Sacharomyces are detected [193].…”

Section: The Mycobiome and Neurological Disordersmentioning

confidence: 95%

The Mycobiome in Health and Disease: Emerging Concepts, Methodologies and Challenges

et al. 2020

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Fungal disease is an increasingly recognised global clinical challenge associated with high mortality. Early diagnosis of fungal infection remains problematic due to the poor sensitivity and specificity of current diagnostic modalities. Advances in sequencing technologies hold promise in addressing these shortcomings and for improved fungal detection and identification. To translate such emerging approaches into mainstream clinical care will require refinement of current sequencing and analytical platforms, ensuring standardisation and consistency through robust clinical benchmarking and its validation across a range of patient populations. In this stateof-the-art review, we discuss current diagnostic and therapeutic challenges associated with fungal disease and provide key examples where the application of sequencing technologies has potential diagnostic application in assessing the human 'mycobiome'. We assess how ready access to fungal sequencing may be exploited in broadening our insight into hostfungal interaction, providing scope for clinical diagnostics and the translation of emerging mycobiome research into clinical practice.

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“…No Trichosporon DNA seems to be present in the datasets from [1], neither in the MS nor the non-MS samples. This may not be surprising as the central nervous system is not directly in contact with the CSF.…”

Section: Resultsmentioning

confidence: 86%

“…With recent doubts about the sterility of the CNS [3], and the report of Trichosporon in MS patients' nerve tissue [2] we tried to add information to the discussion by 2 looking at public WMGS sequencing datasets of human CSF samples. The only public datasets from MS patients are well described in [1], where bacteria and virii were examined. The data is of good depth to allow reclassification for fungi.…”

Section: Introductionmentioning

confidence: 99%

Metagenomic datasets of cerebrospinal fluid from a small cohort of MS/non-MS patients do not show DNA from the fungal genus Trichosporon

Stephan¹

2018

Preprint

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In [2] Alonso et al used nested PCR assays together with next-generation sequencing to find Trichosporon species in the nervous tissue of 10 patients with MS. We deemed it possible that the fungus would be present in cerebrospinal fluid (CSF) samples. Whole metagenomic shotgun (WMGS) sequencing allows detection of any organism in a sample. With Trichosporon any detection would be a true positive because these fungi are not known to be on the skin, or as typical lab contamination. We screened public WMGS datasets of CSF from a cohort of 43 Canadian patients (28 MS, 13 non-MS)[1], using Kraken2[7], the ultrafast kmer-based classifier, using a fungal database augmented with all cleaned available Trichosporon genome assemblies from the NCBI. Blasting the marked reads against an equally augmented blastn database revealed no alignments with an evalue <= 1e-50. In general Kraken2 marked not more than 5 consecutive kmers in any read, which is a clear negative.

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Cerebrospinal Fluid in a Small Cohort of Patients with Multiple Sclerosis Was Generally Free of Microbial DNA

Cited by 12 publications

References 58 publications

Rhamnolipids, Microbial Virulence Factors, in Alzheimer’s Disease

Rhamnolipids, Microbial Virulence Factors, in Alzheimer’s Disease

The Mycobiome in Health and Disease: Emerging Concepts, Methodologies and Challenges

Metagenomic datasets of cerebrospinal fluid from a small cohort of MS/non-MS patients do not show DNA from the fungal genus Trichosporon

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