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Series GSE235754 Query DataSets for GSE235754
Status Public on Jun 30, 2023
Title Mycobacterium tuberculosis Rv0102-regulated copper uptake facilitates bacterial escape from phagolysosome
Organism Danio rerio
Experiment type Expression profiling by high throughput sequencing
Summary The host restricts Mycobacterium tuberculosis (Mtb) access of transition metal ions to inhibit its growth. Cu is essential for the survival of Mtb, but Cu excess is toxic. During co-evolution, Mtb has developed various mechanisms to maintain copper homeostasis. In this report, we firstly found Mtb Rv0102 encoded membrane protein is critical for Mycobacterium Cu uptake. The intracellular Cu level of M. smegmatis (Ms) Rv0102 homolog MSMEG_4702 knockout strain decreased threefold than the wild type, the deletion mutant was more tolerant to higher Cu level. This indicates that Rv0102 is significant for Cu homeostasis and resistance to Cu toxicity. Knocking out the homologous gene MMAR_0267 in M. marinum (Mm) also enhanced its virulence in zebrafish and improved its survival within macrophages. In THP-1 cells infected with Mm, Mm MMAR_0267 deletion mutants’ intracellular survival increased fourfolds and accompanied by less cell apoptosis. Cu deficiency down-regulates the transcription of the M. marinum virulence factor CFP-10, dampening the STING cytosolic signaling in macrophages, fewer IFN-β and less cell apoptosis. These results suggest that Cu is an important factor in inducing cell apoptosis. In summary, mycobacteria can effectively counteract the host's early key nutritional immune mechanisms by regulating copper metabolism, to increase its virulence.
Overall design Injected zebrafish with WT, ΔMMAR_0267 and ΔMMAR_0267:: MMAR_0267 M. marinum. Performed RNA-seq analysis of zebrafish livers.
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Submission date Jun 26, 2023
Last update date Jun 30, 2023
Contact name Hongxiang Xu
Organization name Southwest University
Street address Tiansheng Road
City Chongqing
ZIP/Postal code 400715
Country China
Platforms (1)
GPL24995 Illumina NovaSeq 6000 (Danio rerio)
Samples (9)
GSM7508880 Zebrafish_WT1
GSM7508881 Zebrafish_WT2
GSM7508882 Zebrafish_WT3
BioProject PRJNA987565

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Supplementary file Size Download File type/resource
GSE235754_raw_counts.txt.gz 387.1 Kb (ftp)(http) TXT
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