Bacterial nucleomodulins and cancer: An unresolved enigma

Khan, Abdul Arif; Khan, Zakir

doi:10.1016/j.tranon.2020.100922

Cited by 5 publications

(2 citation statements)

References 95 publications

(63 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Over the past decade, researches have increasingly uncovered the ability of bacterial pathogens in mammals and plants to directly target cellular nuclei by their nucleomodulin proteins. Nucleomodulins are secreted proteins of bacteria that enter into the nuclei of host cells and control the expression of crucial genes involved in important host responses, such as immunity, cell proliferation, and apoptosis [11,20,[27][28][29][30][31][32][33]. However, the exploration of the secreted nucleomodulins of mycoplasmas is still in its early stages.…”

Section: Discussionmentioning

confidence: 99%

The Identification of a Novel Nucleomodulin MbovP467 of Mycoplasmopsis bovis and Its Potential Contribution in Pathogenesis

Raheem,

Lu,

Khalid

et al. 2024

Cells

View full text Add to dashboard Cite

Mycoplasmopsis bovis is a causative agent of crucial diseases in both dairy and beef cattle leading to substantial economic losses. However, limited control measures for M. bovis-related diseases exist due to a lack of understanding about the virulence factors of this pathogen, a common challenge in mycoplasma research. Consequently, this study aimed to characterize a novel nucleomodulin as a virulence-related factor of M. bovis. Employing bioinformatic tools, we initially predicted MbovP467 to be a secreted protein with a nuclear localization signal based on SignalP scores and the cNLS (Nuclear Localization Signal) Mapper, respectively. Subsequently, the MbovP467 gene was synthesized and cloned into a pEGFP plasmid with EGFP labeling to obtain a recombinant plasmid (rpEGFP-MbovP467) and then was also cloned in pET-30a with a consideration for an Escherichia coli codon bias and expressed and purified for the production of polyclonal antibodies against the recombinant MbovP467 protein. Confocal microscopy and a Western blotting assay confirmed the nuclear location of MbovP467 in bovine macrophages (BoMacs). RNA-seq data revealed 220 up-regulated and 20 down-regulated genes in the rpEGFP-MbovP467-treated BoMac group compared to the control group (pEGFP). A GO- and KEGG-enrichment analysis identified associations with inflammatory responses, G protein-coupled receptor signaling pathways, nuclear receptor activity, sequence-specific DNA binding, the regulation of cell proliferation, IL-8, apoptotic processes, cell growth and death, the TNF signaling pathway, the NF-κB signaling pathway, pathways in cancer, and protein families of signaling and cellular processes among the differentially expressed up-regulated mRNAs. Further experiments, investigating cell viability and the inflammatory response, demonstrated that MbovP467 reduces BoMac cell viability and induces the mRNA expression of IL-1β, IL-6, IL-8, TNF-α, and apoptosis in BoMac cells. Further, MbovP467 increased the promoter activity of TNF-α. In conclusion, this study identified a new nucleomodulin, MbovP467, for M. bovis, which might have an important role in M. bovis pathogenesis.

show abstract

Section: Discussionmentioning

confidence: 99%

The Identification of a Novel Nucleomodulin MbovP467 of Mycoplasmopsis bovis and Its Potential Contribution in Pathogenesis

Raheem,

Lu,

Khalid

et al. 2024

Cells

View full text Add to dashboard Cite

show abstract

“…Several bacteria are known to produce certain proteins known as nucleomodulins with the ability to alter normal nuclear function and thereby influence cell growth. These nucleomodulins are also identified in bacteria suspiciously associated with cancer, thereby indicate towards potential involvement of these proteins in carcinogenesis [32]. In contrast, microbiota also has ability to both promote and inhibit cell death through regulating apoptosis and therefore contributing in intestinal mucosal epithelial cell inflammation and integrity [33].…”

Section: Influence On Cell Growthmentioning

confidence: 99%

Microbiota and cancer: current understanding and mechanistic implications

et al. 2021

Self Cite

View full text Add to dashboard Cite

During last few decades, role of microbiota and its importance in several diseases has been a hot topic for research. The microbiota is considered as an accessory organ for maintaining normal physiology of an individual. These microbiota organisms which normally colonize several epithelial surfaces are known to secrete several small molecules leading to local and systemic effects on normal biological processes. The role of microbiota is also established in carcinogenesis as per several recent findings. The effects of microbiota on cancer is not only limited to their contribution in oncogenesis, but the overall susceptibility for oncogenesis and its subsequent progression, development of coinfections, and response to anticancer therapy is also found to be affected by microbiota. The information about microbiota and subsequent contributions of microbes in anticancer response motivated researchers in development of microbes-based anticancer therapeutics. We provided current status of microbiota contribution in oncogenesis with special reference to their mechanistic implications in different aspects of oncogenesis. In addition, the mechanistic implications of bacteria in anticancer therapy are also discussed. We conclude that several mechanisms of microbiota-mediated regulation of oncogenesis is known, but approaches must be focused on understanding contribution of microbiota as a community rather than single organisms-mediated effects.

show abstract