Dataset Information

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

ABSTRACT: Cancer was initially considered a genetic disease. However, recent studies have revealed the connection between bacterial infections and growth of different types of cancer. The enteroinvasive strain of Mycoplasma hominis alters the normal behavior of host cells that may result in the growth of prostate cancer. The role of M. hominis in the growth and development of prostate cancer still remains unclear. The infection may regulate several factors that influence prostate cancer growth in susceptible individuals. The aim of this study was to predict M. hominis proteins targeted into the endoplasmic reticulum (ER) of the host cell, and their potential role in the induction of prostate cancer. From the whole proteome of M. hominis, 19 proteins were predicted to be targeted into the ER of host cells. The results of our study predict that several proteins of M. hominis may be targeted to the host cell ER, and possibly alter the normal pattern of protein folding. These predicted proteins can modify the normal function of the host cell. Thus, the intercellular infection of M. hominis in host cells may serve as a potential factor in prostate cancer etiology.

SUBMITTER: Zakariah M

PROVIDER: S-EPMC6099661 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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

Zakariah Mohammed M Khan Shahanavaj S Chaudhary Anis Ahmad AA Rolfo Christian C Rolfo Christian C Ben Ismail Mohamed Maher MM Alotaibi Yousef Ajami YA

Molecules (Basel, Switzerland) 20180424 5

Cancer was initially considered a genetic disease. However, recent studies have revealed the connection between bacterial infections and growth of different types of cancer. The enteroinvasive strain of Mycoplasma hominis alters the normal behavior of host cells that may result in the growth of prostate cancer. The role of M. hominis in the growth and development of prostate cancer still remains unclear. The infection may regulate several factors that influence prostate cancer grow ...[more]

PMID: 29695086

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Project description:BACKGROUND:Mycoplasma hominis is a human urogenital pathogen involved in gynaecological, neonatal and extra-genital infections. However, no versatile genetic tools are currently available to study the pathogenicity of this bacterium. Targeting-Induced Local Lesions IN Genomes (TILLING) is a reverse-genetic method that combines point mutations induced by chemical mutagenesis with a DNA screening technique. We used ethyl methanesulfonate (EMS) that introduces C-G to T-A transition mutations to generate a library of M. hominis mutants. As a proof of concept, mutagenized organisms were screened for mutations in two target genes previously associated with the mycoplasma pathogenicity, the vaa gene encoding an adhesin lipoprotein and the oppA gene encoding the main ectoATPase of the bacterium. The resulting mutants were evaluated using functional assays, an adhesion to HeLa cell assay for vaa-mutants and an ATPase activity test for oppA-mutants. RESULTS:A 1200-clone library was generated by exposing M. hominis PG21 to 9 mg/mL EMS for 3 h. To identify mutants of interest, targeted gene fragments were amplified, heat-denatured, slowly reannealed and digested with the mismatch-specific endonuclease ENDO1. If multiple alleles were present in the PCR amplicons, these alleles formed heteroduplexes during reannealing that were specifically cleaved by ENDO1 at mismatching positions. A total of four vaa-mutants and two oppA-mutants harbouring missense mutations were obtained and fully sequenced. Zero to eight additional mutations were identified in the genomes of each mutant. The vaa-mutants were tested for adhesion to immobilized HeLa cells but their adhesion was not significantly different from the adhesion of M. hominis PG21. One of the two oppA-mutants that were tested for ATPase activity presented a higher affinity for its ATP substrate than the parental strain. CONCLUSION:For the first time, we demonstrated that M. hominis gene-targeted mutants could be successfully obtained using this TILLING strategy. In the absence of robust genetic tools for studying M. hominis, the TILLING strategy that can target any gene of the genome could help to elucidate gene functions and to better understand the pathogenesis of this human pathogenic species.

Project description:Hypertrophic cardiomyopathy (HCM) is mainly associated with myosin, heavy chain 7 (MYH7) and myosin binding protein C, cardiac (MYBPC3) mutations. In order to better explain the clinical and genetic heterogeneity in HCM patients, in this study, we implemented a target-next generation sequencing (NGS) assay. An Ion AmpliSeq™ Custom Panel for the enrichment of 19 genes, of which 9 of these did not encode thick/intermediate and thin myofilament (TTm) proteins and, among them, 3 responsible of HCM phenocopy, was created. Ninety-two DNA samples were analyzed by the Ion Personal Genome Machine: 73 DNA samples (training set), previously genotyped in some of the genes by Sanger sequencing, were used to optimize the NGS strategy, whereas 19 DNA samples (discovery set) allowed the evaluation of NGS performance. In the training set, we identified 72 out of 73 expected mutations and 15 additional mutations: the molecular diagnosis was achieved in one patient with a previously wild-type status and the pre-excitation syndrome was explained in another. In the discovery set, we identified 20 mutations, 5 of which were in genes encoding non-TTm proteins, increasing the diagnostic yield by approximately 20%: a single mutation in genes encoding non-TTm proteins was identified in 2 out of 3 borderline HCM patients, whereas co-occuring mutations in genes encoding TTm and galactosidase alpha (GLA) altered proteins were characterized in a male with HCM and multiorgan dysfunction. Our combined targeted NGS-Sanger sequencing-based strategy allowed the molecular diagnosis of HCM with greater efficiency than using the conventional (Sanger) sequencing alone. Mutant alleles encoding non-TTm proteins may aid in the complete understanding of the genetic and phenotypic heterogeneity of HCM: co-occuring mutations of genes encoding TTm and non-TTm proteins could explain the wide variability of the HCM phenotype, whereas mutations in genes encoding only the non-TTm proteins are identifiable in patients with a milder HCM status.

Dataset Information

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

Publications

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

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