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Modulatory Impact of the sRNA Mcr11 in Two Clinical Isolates of Mycobacterium tuberculosis

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Abstract

Mycobacterium tuberculosis (Mtb) is a successful pathogen causing tuberculosis (TB) disease in humans. It has been shown, that some circulating strains of Mtb in TB endemic populations, are more virulent and more transmissible than others, which may be related to their evolved adaptations to modulate the host immune responses. Underlying these adaptations to the stressful conditions, different genetic regulatory networks involved sRNAs that are mostly unknown for Mtb. We have previously shown that Mcr11 is one of the main sRNAs that determine transcriptomic differences among the Colombian clinical isolates UT127 and UT205 compared to the laboratory strain H37Rv. We found that the knock-down of mcr11 using CRISPRi has a major impact on phenotypic traits, especially in the clinical isolate UT205. Through the analysis of RNA-seq during the knock-down of mcr11 in UT205, we found a downregulation of genes mainly involved in lipid synthesis, lipid metabolism, ribosomal proteins, transport systems, respiratory and energy systems, membrane and cell wall components, intermediary metabolism, lipoproteins and virulence genes. One of the most interesting genes showing transcriptomic changes is OprA (encoded by the gene rv0516c), which has been involved in the K+ regulation. Overall, our data may suggest that one of the prominent roles of the sRNA Mcr11 is to regulate genes that control Mtb growth and osmoregulation.

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Data Availability

The transcriptomic data from the RNA-seq of the laboratory strain H37Rv was deposited in https://www.ncbi.nlm.nih.gov/sra under the Bioproject: PRJNA565699, codes: SAMN12766833, SAMN12766690, SAMN12766936, SAMN12771737, SAMN12766379, and SAMN12766853. All other data are fully available without restriction.

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Acknowledgements

We would like to thank Prof. Sarah Fortune (School of Public Health, Harvard University) for the kind gift of the CRISPRi plasmids. We acknowledge “Contrato de acceso a recursos genéticos y sus productos derivados. Resolución No.666 del 27-marzo-2017”. We like to thank “Estrategia de Sostenibilidad” Universidad de Antioquia.

Funding

This work was supported by funding from Colciencias Grant # 111571250266 and CODI # 2015-6726.

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Conceived and designed experiments: AB, KLFAE, and LFB. Performed the experiments: AB, KLFAE, and LMMM. Analyzed the data: AB, KLFAE, LMMM., LFB and JFA. Wrote and revise the manuscript: AB, KLFAE, LFB and JFA.

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Correspondence to Andres Baena.

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Alvarez-Eraso, K.L.F., Muñoz-Martínez, L.M., Alzate, J.F. et al. Modulatory Impact of the sRNA Mcr11 in Two Clinical Isolates of Mycobacterium tuberculosis. Curr Microbiol 79, 39 (2022). https://doi.org/10.1007/s00284-021-02733-0

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