Refine
Has Fulltext
- yes (13)
Is part of the Bibliography
- yes (13)
Year of publication
- 2020 (13) (remove)
Document Type
- Journal article (13) (remove)
Language
- English (13)
Keywords
- antibiotics (3)
- RNA-seq (2)
- vancomycin (2)
- AcrAB-TolC efflux pump (1)
- CRISPR-Cas system (1)
- Candida albicans (1)
- Candida auris (1)
- FinO family (1)
- Gram-positive bacteria (1)
- HFQ (1)
- Methanosarcina mazei (1)
- Neisseria meningitidis (1)
- RNA sequencing (1)
- Salmonella (1)
- Snf1 (1)
- adaptation phase (1)
- adhesion (1)
- antibiotic (1)
- atypical tetracyclines (1)
- bacterial resistance (1)
- biofilm (1)
- broad-spectrum antibiotics (1)
- casposon (1)
- chaperone (1)
- chelocardins (1)
- clinical isolates (1)
- conditional mutants (1)
- drug design (1)
- dual function (1)
- enterococci (1)
- epithelial cells (1)
- essential genes (1)
- fatty acids (1)
- fluconazole resistance (1)
- gene expression (1)
- genomics (1)
- glycopeptide antibiotics (1)
- host (1)
- in vitro (1)
- in vivo (1)
- infectious disease (1)
- invasion (1)
- mechanism of resistance (1)
- methanoarchaea (1)
- microbiome (1)
- microenvironment (1)
- multidrug-resistant bacteria (1)
- natural transformation (1)
- organohalide respiration (1)
- peptide conjugates (1)
- polycationic peptides (1)
- post-transcriptional regulation (1)
- protein kinases (1)
- regulator (1)
- resistance-breaking properties (1)
- responses (1)
- sRNA atlas (1)
- sequence (1)
- small RNA (1)
- sortase A (1)
- stem cells (1)
- structural modification (1)
- tetrachloroethene (1)
- transcription factor (1)
- transcription start sites (1)
- transcriptional regulation (1)
- transcriptome (1)
- transcriptomics (1)
- translocation (1)
- two‐component system (1)
- urinary tract infection (UTI) (1)
- uropathogens (1)
- virulence (1)
Institute
- Institut für Molekulare Infektionsbiologie (13) (remove)
Energy conservation via organohalide respiration (OHR) in dehalogenating Sulfurospirillum species is an inducible process. However, the gene products involved in tetrachloroethene (PCE) sensing and signal transduction have not been unambiguously identified. Here, genome sequencing of Sulfurospirillum strains defective in PCE respiration and comparative genomics, which included the PCE‐respiring representatives of the genus, uncovered the genetic inactivation of a two‐component system (TCS) in the OHR gene region of the natural mutants. The assumption that the TCS gene products serve as a PCE sensor that initiates gene transcription was supported by the constitutive low‐level expression of the TCS operon in fumarate‐adapted cells of Sulfurospirillum multivorans. Via RNA sequencing, eight transcriptional units were identified in the OHR gene region, which includes the TCS operon, the PCE reductive dehalogenase operon, the gene cluster for norcobamide biosynthesis, and putative accessory genes with unknown functions. The OmpR‐family response regulator (RR) encoded in the TCS operon was functionally characterized by promoter‐binding assays. The RR bound a cis‐regulatory element that contained a consensus sequence of a direct repeat (CTATW) separated by 17 bp. Its location either overlapping the −35 box or 50 bp further upstream indicated different regulatory mechanisms. Sequence variations in the regulator binding sites identified in the OHR gene region were in accordance with differences in the transcript levels of the respective gene clusters forming the PCE regulon. The results indicate the presence of a fine‐tuned regulatory network controlling PCE metabolism in dehalogenating Sulfurospirillum species, a group of metabolically versatile organohalide‐respiring bacteria.
ABSTRACT The recently emerged pathogenic yeast Candida auris is a major concern for human health, because it is easily transmissible, difficult to eradicate from hospitals, and highly drug resistant. Most C. auris isolates are resistant to the widely used antifungal drug fluconazole due to mutations in the target enzyme Erg11 and high activity of efflux pumps, such as Cdr1. In the well-studied, distantly related yeast Candida albicans, overexpression of drug efflux pumps also is a major mechanism of acquired fluconazole resistance and caused by gain-of-function mutations in the zinc cluster transcription factors Mrr1 and Tac1. In this study, we investigated a possible involvement of related transcription factors in efflux pump expression and fluconazole resistance of C. auris. The C. auris genome contains three genes encoding Mrr1 homologs and two genes encoding Tac1 homologs, and we generated deletion mutants lacking these genes in two fluconazole-resistant strains from clade III and clade IV. Deletion of TAC1b decreased the resistance to fluconazole and voriconazole in both strain backgrounds, demonstrating that the encoded transcription factor contributes to azole resistance in C. auris strains from different clades. CDR1 expression was not or only minimally affected in the mutants, indicating that Tac1b can confer increased azole resistance by a CDR1-independent mechanism.
IMPORTANCE Candida auris is a recently emerged pathogenic yeast that within a few years after its initial description has spread all over the globe. C. auris is a major concern for human health, because it can cause life-threatening systemic infections, is easily transmissible, and is difficult to eradicate from hospital environments. Furthermore, C. auris is highly drug resistant, especially against the widely used antifungal drug fluconazole. Mutations in the drug target and high activity of efflux pumps are associated with azole resistance, but it is not known how drug resistance genes are regulated in C. auris. We have investigated the potential role of several candidate transcriptional regulators in the intrinsic fluconazole resistance of C. auris and identified a transcription factor that contributes to the high resistance to fluconazole and voriconazole of two C. auris strains from different genetic clades, thereby providing insight into the molecular basis of drug resistance of this medically important yeast."
Enterococcus faecalis and faecium are two major representative clinical strains of the Enterococcus genus and are sadly notorious to be part of the top agents responsible for nosocomial infections. Despite their critical implication in worldwide public healthcare, essential and available resources such as deep transcriptome annotations remain poor, which also limits our understanding of post-transcriptional control small regulatory RNA (sRNA) functions in these bacteria. Here, using the dRNA-seq technique in combination with ANNOgesic analysis, we successfully mapped and annotated transcription start sites (TSS) of both E. faecalis V583 and E. faecium AUS0004 at single nucleotide resolution. Analyzing bacteria in late exponential phase, we capture ~40% (E. faecalis) and 43% (E. faecium) of the annotated protein-coding genes, determine 5′ and 3′ UTR (untranslated region) length, and detect instances of leaderless mRNAs. The transcriptome maps revealed sRNA candidates in both bacteria, some found in previous studies and new ones. Expression of candidate sRNAs is being confirmed under biologically relevant environmental conditions. This comprehensive global TSS mapping atlas provides a valuable resource for RNA biology and gene expression analysis in the Enterococci. It can be accessed online at www.helmholtz-hiri.de/en/datasets/enterococcus through an instance of the genomic viewer JBrowse.