Using molecular-mimicry-inducing pathways of pathogens as novel drug targets

Garg, Anjali; Kumari, Bandana; Singhal, Neelja; Kumar, Manish

doi:10.1016/j.drudis.2018.10.010

Cited by 7 publications

(5 citation statements)

References 32 publications

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“…Thus, molecular mimicry goes beyond the similarity of structures between the host proteome and the microbiome and includes genetic, environmental factors and alterations that are related to the selection processes of T cells in the thymus that allow the filtration of self-reactive cells ( 100 ), which makes this mechanism an interesting therapeutic target that is already being explored ( 101 ).…”

Section: Introductionmentioning

confidence: 99%

Oral Dysbiosis and Autoimmunity: From Local Periodontal Responses to an Imbalanced Systemic Immunity. A Review

et al. 2020

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The current paradigm of onset and progression of periodontitis includes oral dysbiosis directed by inflammophilic bacteria, leading to altered resolution of inflammation and lack of regulation of the inflammatory responses. In the construction of explanatory models of the etiopathogenesis of periodontal disease, autoimmune mechanisms were among the first to be explored and historically, for more than five decades, they have been described in an isolated manner as part of the tissue damage process observed in periodontitis, however direct participation of these mechanisms in the tissue damage is still controversial. Autoimmunity is affected by genetic and environmental factors, leading to an imbalance between the effector and regulatory responses, mostly associated with failed resolution mechanisms. However, dysbiosis/infection and chronic inflammation could trigger autoimmunity by several mechanisms including bystander activation, dysregulation of toll-like receptors, amplification of autoimmunity by cytokines, epitope spreading, autoantigens complementarity, autoantigens overproduction, microbial translocation, molecular mimicry, superantigens, and activation or inhibition of receptors related to autoimmunity by microorganisms. Even though autoreactivity in periodontitis is biologically plausible, the associated mechanisms could be related to non-pathologic responses which could even explain non-recognized physiological functions. In this review we shall discuss from a descriptive point of view, the autoimmune mechanisms related to periodontitis physio-pathogenesis and the participation of oral dysbiosis on local periodontal autoimmune responses as well as on different systemic inflammatory diseases.

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Section: Introductionmentioning

confidence: 99%

Oral Dysbiosis and Autoimmunity: From Local Periodontal Responses to an Imbalanced Systemic Immunity. A Review

et al. 2020

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“…During preliminary screenings, the pure colonies appearing Gram-positive 1). Haemolytic activity is an indication of the presence of haemolysin enzymes and cytotoxic phospholipases in micro-organisms (Sorokulova et al 2008;Pan et al 2014;Garg et al 2019). As reported earlier, complete haemolysis (β) of red blood cells observed during in vitro screening could discriminate pathogenic and non-pathogenic species, and γ and α-haemolysis are considered safe characteristic for Bacillus strains (Shin et al 2012;Zulkhairi Amin et al 2019), Hence, during the course of study the respective Bacillus isolates demonstrating γ and αhaemolysis were selected for further screening.…”

Section: Resultsmentioning

confidence: 97%

“…2014; Garg et al . 2019). As reported earlier, complete haemolysis (β) of red blood cells observed during in vitro screening could discriminate pathogenic and non‐pathogenic species, and γ and α‐haemolysis are considered safe characteristic for Bacillus strains (Shin et al .…”

Section: Resultsmentioning

confidence: 99%

In vitro probiotic and safety attributes of Bacillus spp. isolated from beebread, honey samples and digestive tract of honeybees Apis mellifera

Toutiaee

Mojgani

Harzandi

et al. 2022

Letters in Applied Microbiology

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Bacillus species isolated from honeybee Apis mellifera gut, honey and bee bread samples were characterized for their in vitro probiotic and safety attributes. Alpha and γ haemolytic cultures were tested for their antibiotic resistance, antibacterial spectrum, acid and bile tolerance, adhesion ability (auto‐aggregation, co‐aggregation and hydrophobicity) and phenol tolerance. Safety criteria included evaluation of virulence genes and cytotoxicity percentages. Bacillus isolates inhibited both Gram‐positive and Gram‐negative pathogens including Staphylococcus aureus, Pseudomonas aeruginosa, Enterococcus faecalis and Streptococcus mutans, while none could inhibit Listeria monocytogenes. Among the isolates, Bacillus subtilis ZH05, ZB03 and ZG025 showed resistance to most of the tested antibiotics and were considered unsafe. B. subtilis (4) and B. licheniformis (1) tolerated acidic pH and bile conditions, never the less were more tolerant in simulated intestinal conditions vis‐a‐vis gastric conditions. In 0·5% phenol concentrations, B. licheniformis ZH02 showed highest growth, while, B. subtilis ZG029 demonstrated highest auto‐aggregation (65 ± 4·6) and hydrophobicity (23 ± 3·6) percentages (P < 0·05). The isolates lacked virulence genes (hblA, hblC, hblD, nhe, cytK and ces), and their cytotoxic percentage on Caco‐2 cell lines was ˂15%. Overall, honeybees appear to be a good source of Bacillus species exhibiting typical in vitro probiotic properties, which could be of commercial interest.

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“…Novosphingobium aromaticivorans has two lipoylated proteins with greater homology to human PDC-E2 (7). Mimicry peptides of human PDC-E2 and evidence of cross-reactive antibodies were also observed for Mycoplasma pneumonia, Lactobacillus delbrueckii and Mycobacterium gordonae (2,8). Third, microbial by-products may affect PBC.…”

Section: Introductionmentioning

confidence: 98%

The Salivary Microbiota of Patients With Primary Biliary Cholangitis Is Distinctive and Pathogenic

Jiang

Chen

et al. 2021

Front. Immunol.

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The role of host-microbiota interactions in primary biliary cholangitis (PBC) has received increased attention. However, the impact of PBC on the oral microbiota and contribution of the oral microbiota to PBC are unclear. In this study, thirty-nine PBC patients without other diseases and 37 healthy controls (HCs) were enrolled and tested for liver functions and haematological variables. Saliva specimens were collected before and after brushing, microbiota was determined using 16S rDNA sequencing, metabolomics was profiled using Gas Chromatography-Mass Spectrometer (GC-MS), 80 cytokines were assayed using biochips, and inflammation inducibility was evaluated using OKF6 keratinocytes and THP-1 macrophages. Finally, the effect of ultrasonic scaling on PBC was estimated. Compared with HCs, PBC saliva had enriched taxa such as Bacteroidetes, Campylobacter, Prevotella and Veillonella and depleted taxa such as Enterococcaceae, Granulicatella, Rothia and Streptococcus. PBC saliva also had enriched sCD163, enriched metabolites such as 2-aminomalonic acid and 1-dodecanol, and depleted metabolites such as dodecanoic acid and propylene glycol. sCD163, 4-hydroxybenzeneacetic acid and 2-aminomalonic acid were significantly correlated with salivary cytokines, bacteria and metabolites. Salivary Veillonellaceae members, 2-aminomalonic acid, and sCD163 were positively correlated with liver function indicators such as serum alkaline phosphatase (ALP), aspartate aminotransferase (AST) and alanine aminotransferase (ALT). PBC salivary microbes induced more soluble interleukin (IL)-6 receptor α (sIL-6Rα), sIL-6Rβ and tumour necrosis factor ligand superfamily (TNFSF)13B from OKF6 keratinocytes, and PBC salivary supernatant induced more IL-6, IL-10, granulocyte-macrophage colony-stimulating factor (GM-CSF), chemokine (C-C motif) ligand (CCL)13, C-X-C motif chemokine (CXC)L1 and CXCL16 from THP-1 macrophages. Toothbrushing significantly reduced the expression of inflammatory cytokines such as IL-1β, IL-8 and TNF-α and harmful metabolites such as cadaverine and putrescine in PBC but not HC saliva after P‐value correction. The levels of ALP and bilirubin in PBC serum were decreased after ultrasonic scaling. Together, PBC patients show significant alterations in their salivary microbiota, likely representing one cause and treatment target of oral inflammation and worsening liver functions.

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Using molecular-mimicry-inducing pathways of pathogens as novel drug targets

Cited by 7 publications

References 32 publications

Oral Dysbiosis and Autoimmunity: From Local Periodontal Responses to an Imbalanced Systemic Immunity. A Review

Oral Dysbiosis and Autoimmunity: From Local Periodontal Responses to an Imbalanced Systemic Immunity. A Review

In vitro probiotic and safety attributes of Bacillus spp. isolated from beebread, honey samples and digestive tract of honeybees Apis mellifera

The Salivary Microbiota of Patients With Primary Biliary Cholangitis Is Distinctive and Pathogenic

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