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1.
Microorganisms ; 9(10)2021 Oct 14.
Article in English | MEDLINE | ID: mdl-34683468

ABSTRACT

Serine/threonine kinase PknB and its corresponding phosphatase Stp are important regulators of many cell functions in the pathogen S. aureus. Genome-scale gene expression data of S. aureus strain NewHG (sigB+) elucidated their effect on physiological functions. Moreover, metabolic modelling from these data inferred metabolic adaptations. We compared wild-type to deletion strains lacking pknB, stp or both. Ser/Thr phosphorylation of target proteins by PknB switched amino acid catabolism off and gluconeogenesis on to provide the cell with sufficient components. We revealed a significant impact of PknB and Stp on peptidoglycan, nucleotide and aromatic amino acid synthesis, as well as catabolism involving aspartate transaminase. Moreover, pyrimidine synthesis was dramatically impaired by stp deletion but only slightly by functional loss of PknB. In double knockouts, higher activity concerned genes involved in peptidoglycan, purine and aromatic amino acid synthesis from glucose but lower activity of pyrimidine synthesis from glucose compared to the wild type. A second transcriptome dataset from S. aureus NCTC 8325 (sigB-) validated the predictions. For this metabolic adaptation, PknB was found to interact with CdaA and the yvcK/glmR regulon. The involved GlmR structure and the GlmS riboswitch were modelled. Furthermore, PknB phosphorylation lowered the expression of many virulence factors, and the study shed light on S. aureus infection processes.

2.
Int J Mol Sci ; 22(5)2021 Mar 05.
Article in English | MEDLINE | ID: mdl-33807854

ABSTRACT

We observed substantial differences in predicted Major Histocompatibility Complex II (MHCII) epitope presentation of SARS-CoV-2 proteins for different populations but only minor differences in predicted MHCI epitope presentation. A comparison of this predicted epitope MHC-coverage revealed for the early phase of infection spread (till day 15 after reaching 128 observed infection cases) highly significant negative correlations with the case fatality rate. Specifically, this was observed in different populations for MHC class II presentation of the viral spike protein (p-value: 0.0733 for linear regression), the envelope protein (p-value: 0.023), and the membrane protein (p-value: 0.00053), indicating that the high case fatality rates of COVID-19 observed in some countries seem to be related with poor MHC class II presentation and hence weak adaptive immune response against these viral envelope proteins. Our results highlight the general importance of the SARS-CoV-2 structural proteins in immunological control in early infection spread looking at a global census in various countries and taking case fatality rate into account. Other factors such as health system and control measures become more important after the early spread. Our study should encourage further studies on MHCII alleles as potential risk factors in COVID-19 including assessment of local populations and specific allele distributions.


Subject(s)
COVID-19/mortality , Histocompatibility Antigens Class II/genetics , Histocompatibility Antigens Class II/immunology , SARS-CoV-2/chemistry , Viral Structural Proteins/chemistry , Adaptive Immunity , Alleles , COVID-19/immunology , COVID-19/transmission , Computational Biology/methods , Correlation of Data , Epitopes, B-Lymphocyte/genetics , Epitopes, B-Lymphocyte/immunology , Epitopes, T-Lymphocyte/genetics , Epitopes, T-Lymphocyte/immunology , HLA Antigens/genetics , Histocompatibility Antigens Class I/genetics , Histocompatibility Antigens Class I/immunology , Humans , Mortality , SARS-CoV-2/immunology , Viral Structural Proteins/immunology
3.
Emerg Infect Dis ; 25(9): 1763-1765, 2019 09.
Article in English | MEDLINE | ID: mdl-31223105

ABSTRACT

The emerging yeast Candida auris has disseminated worldwide. We report on 7 cases identified in Germany during 2015-2017. In 6 of these cases, C. auris was isolated from patients previously hospitalized abroad. Whole-genome sequencing and epidemiologic analyses revealed that all patients in Germany were infected with different strains.


Subject(s)
Antifungal Agents/therapeutic use , Candida/isolation & purification , Candidiasis/epidemiology , Antifungal Agents/administration & dosage , Antifungal Agents/pharmacology , Candida/drug effects , Candida/genetics , Candidiasis/microbiology , Drug Administration Schedule , Germany/epidemiology , Humans , Microbial Sensitivity Tests , Travel , Whole Genome Sequencing
4.
Genome Announc ; 4(3)2016 Jun 02.
Article in English | MEDLINE | ID: mdl-27257206

ABSTRACT

Here, we report the draft genome sequence of Arthrobacter enclensis NCIM 5488(T), an actinobacterium isolated from a marine sediment sample from Chorao Island, Goa, India. This draft genome sequence consists of 4,226,231 bp with a G+C content of 67.08%, 3,888 protein-coding genes, 50 tRNAs, and 10 rRNAs. Analysis of the genome using bioinformatics tools such as antiSMASH and NaPDoS showed the presence of many unique natural product biosynthetic gene clusters.

5.
Genom Data ; 8: 72-6, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27222803

ABSTRACT

Advances in de novo sequencing technologies allow us to track deeper insights into microbial genomes for restructuring events during the course of their evolution inside and outside the host. Bacterial species belonging to Ochrobactrum genus are being reported as emerging, and opportunistic pathogens in this technology driven era probably due to insertion and deletion of genes. The Ochrobactrum intermedium M86 was isolated in 2005 from a case of non-ulcer dyspeptic human stomach followed by its first draft genome sequence in 2009. Here we report re-sequencing of O. intermedium M86 laboratory adapted strain in terms of gain and loss of genes. We also attempted for finer scale genome sequence with 10 times more genome coverage than earlier one followed by comparative evaluation on Ion PGM and Illumina MiSeq. Despite their similarities at genomic level, lab-adapted strain mainly lacked genes encoding for transposase protein, insertion elements family, phage tail-proteins that were not detected in original strain on both chromosomes. Interestingly, a 5 kb indel was detected in chromosome 2 that was absent in original strain mapped with phage integrase gene of Rhizobium spp. and may be acquired and integrated through horizontal gene transfer indicating the gene loss and gene gain phenomenon in this genus. Majority of indel fragments did not match with known genes indicating more bioinformatic dissection of this fragment. Additionally we report genes related to antibiotic resistance, heavy metal tolerance in earlier and re-sequenced strain. Though SNPs detected, there did not span urease and flagellar genes. We also conclude that third generation sequencing technologies might be useful for understanding genomic architecture and re-arrangement of genes in the genome due to their ability of larger coverage that can be used to trace evolutionary aspects in microbial system.

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