In SilicoPrediction ofEscherichia coliProteins Targeting the Host Cell Nucleus, with Special Reference to Their Role in Colon Cancer Etiology

Abstract

The potential role of Escherichia coli in the development of colorectal carcinoma (CRC) has been investigated in many studies. Although the exact mechanism is not clear, chronic inflammation caused by E. coli and other related events are suggested as possible causes behind E. coli-induced colon cancer. It has been found that CRC cells, but not normal cells, are colonized by an intracellular form of E. coli. We predicted nuclear targeting of bacterial proteins in the host cell through computational tools nuclear localization signal (NLS) mapper and balanced subcellular localization predictor (BaCeILo). During intracellular E. coli residence, such targeting is highly likely and may have a possible role in colon cancer etiology. We observed that several gene expression-associated proteins of E. coli can migrate to the host nucleus during intracellular infections. This situation provides an opportunity for competitive interaction of host and pathogen proteins with similar cellular substrates, thereby increasing the chances of development of colon cancer. Moreover, the results indicated that proteins localized in the membrane of E. coli mostly act as secretary proteins in host cells. No exact correlation was observed between NLS prediction and nuclear localization prediction by BaCeILo. This is partly because of a number of reasons, including that only 30% of nuclear proteins carry NLS and that proteins <40 kDa molecular weight can passively target the host nucleus. This study concludes that detection of gene expression-specific E. coli proteins and their targeting of the nucleus may have a profound impact on CRC etiology.

The Role of Escherichia coli in the Development and Progression of Cancer

“…However, it is unclear whether EspF acts directly on MLH1 and MSH2 or indirectly inducing activation of some transcription factors, which down-regulate MLH1 and MSH2 expression. This hypothesis is supported by previous in vitro and in silico assays, where some nuclear targets for E. coli proteins were described (64,65). Hence, bacterial proteins could enter to cell nucleus and attach to target genes.…”

Computational prediction of Escherichia coli proteins host subcellular targeting and their implications in colorectal cancer etiology

“…Although prediction of NLS in any protein is important for predicting its nuclear localization, the cNLS mapper is a tool to predict NLS activity instead of NLS sequence, and therefore its activity also indicates cytoplasmic targeting of certain proteins [15,18,19]. The role of nucleus targeted E. coli proteins in the CRC etiology is already discussed [8].…”

“…Earlier, we have predicted nuclear targeting of E. coli proteins in host cell during intracellular infection through in silico methods. We have shown that several gene-expression-associated E. coli proteins can migrate to the host nucleus, where they can play pivotal role in colorectal cancer progression [8]. In the present study, we predicted the cytoplasmic and mitochondrial targeting of E. coli proteins in order to lay out a complete picture of E. coli protein localization in the host cell during intracellular infection.…”

To Decipher the Mycoplasma hominis Proteins Targeting into the Endoplasmic Reticulum and Their Implications in Prostate Cancer Etiology Using Next-Generation Sequencing Data

“…The study of protein targeting into the host cell is very important to detect the progression and development of cancer, especially if the cancer growth is associated with the intracellular bacterial infection. The targeting of different bacterial proteins into host cell compartments, such as cytoplasm, mitochondria, and nucleus, has an important effect on the etiology of different cancer types [ 14 , 15 , 38 ]. The host cell gets affected by various types of bacterial proteins, which alter the usual development and normal behavior of the host cell.…”