Dataset Information

Genes and Proteomes Associated With Increased Mutation Frequency and Multidrug Resistance of Naturally Occurring Mismatch Repair-Deficient Salmonella Hypermutators.

ABSTRACT: The emergence of antibiotic-resistant Salmonella through mutations led to mismatch repair (MMR) deficiency that represents a potential hazard to public health. Here, four representative MMR-deficient Salmonella hypermutator strains and Salmonella Typhimurium LT2 were used to comprehensively reveal the influence of MMR deficiency on antibiotic resistance among Salmonella. Our results indicated that the mutation frequency ranged from 3.39 × 10-4 to 5.46 × 10-2 in the hypermutator. Mutation sites in MutS, MutL, MutT, and UvrD of the four hypermutators were all located in the essential and core functional regions. Mutation frequency of the hypermutator was most highly correlated with the extent of mutation in MutS. Mutations in MMR genes (mutS, mutT, mutL, and uvrD) were correlated with increased mutation in antibiotic resistance genes, and the extent of antibiotic resistance was significantly correlated with the number of mutation sites in MutL and in ParC. The number of mutation sites in MMR genes and antibiotic resistance genes exhibited a significant positive correlation with the number of antibiotics resisted and with expression levels of mutS, mutT, and mutL. Compared to Salmonella Typhimurium LT2, a total of 137 differentially expressed and 110 specifically expressed proteins were identified in the four hypermutators. Functional enrichment analysis indicated that the proteins significantly overexpressed in the hypermutators primarily associated with translation and stress response. Interaction network analysis revealed that the ribosome pathway might be a critical factor for high mutation frequency and multidrug resistance in MMR-deficient Salmonella hypermutators. These results help elucidate the mutational dynamics that lead to hypermutation, antibiotic resistance, and activation of stress response pathways in Salmonella.

SUBMITTER: Sheng H

PROVIDER: S-EPMC7225559 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Genes and Proteomes Associated With Increased Mutation Frequency and Multidrug Resistance of Naturally Occurring Mismatch Repair-Deficient Salmonella Hypermutators.

Sheng Huanjing H Huang Jinling J Han Zhaoyu Z Liu Mi M Lü Zexun Z Zhang Qian Q Zhang Jinlei J Yang Jun J Cui Shenghui S Yang Baowei B

Frontiers in microbiology 20200508

The emergence of antibiotic-resistant Salmonella through mutations led to mismatch repair (MMR) deficiency that represents a potential hazard to public health. Here, four representative MMR-deficient Salmonella hypermutator strains and Salmonella Typhimurium LT2 were used to comprehensively reveal the influence of MMR deficiency on antibiotic resistance among Salmonella. Our results indicated that the mutation frequency ranged from 3.39 × 10-4 to 5.46 × 10< ...[more]

PMID: 32457709

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Project description:The aim of this study was to investigate immune response and its prognostic significance in colon carcinomas using the previously described Immunoscore (IS). A population-based series of 779 colorectal cancers, operated on between 2000 and 2010, were classified according to tumour, node, metastasis (TNM) status, mismatch repair (MMR), and BRAF mutation status. Rectal cancer cases (n = 203) were excluded as a high proportion of these patients received preoperative neoadjuvant chemoradiotherapy. Tissue microarray (TMA) samples collected from the tumour centre and invasive front were immunostained for CD3 and CD8. Lymphocytes were then digitally calculated to categorize IS from grade 0 to 4. Samples adequate for IS were available from 510 tumours. IS was significantly associated with AJCC/UICC stage, T stage, lymph node and distant metastases, perineural and lymphovascular invasion, MMR status, and BRAF mutation status. For IS0, IS1, IS2, IS3 and IS4, respectively, the 5-year disease-free survival (DFS) rates were 59, 68, 78, 83 and 94% (p < 0.001); 5-year disease-specific survival (DSS) rates were 47, 55, 75, 80, and 89% (p < 0.001); and 5-year overall survival (OS) rates were 40, 44, 66, 61, and 76% (p < 0.001). IS was also prognostic for DFS, DSS, and OS within subsets of microsatellite-stable (MSS) and microsatellite-instable (MSI) disease. Multivariable analysis showed that IS, AJCC/UICC stage, lymphovascular invasion, and lymph node ratio in AJCC/UICC stage III disease were independent prognostic factors for DFS, DSS, and OS. Age was an independent prognostic factor for DSS and OS. Gender and BRAF mutation were independent prognostic factors for OS. In conclusion, IS differentiated patients with poor versus improved prognosis in MSS and MSI disease and across AJCC/UICC stages. IS, AJCC/UICC stage, lymphovascular invasion, and lymph node ratio in AJCC/UICC stage III disease were independent prognostic factors for DFS, DSS, and OS.

Dataset Information

Genes and Proteomes Associated With Increased Mutation Frequency and Multidrug Resistance of Naturally Occurring Mismatch Repair-Deficient Salmonella Hypermutators.

Publications

Genes and Proteomes Associated With Increased Mutation Frequency and Multidrug Resistance of Naturally Occurring Mismatch Repair-Deficient <i>Salmonella</i> Hypermutators.

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