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<p>We evaluated the response of <i>Mycobacterium tuberculosis</i> to exposure to a new aroylhydrazone derivative using the <i>in vitro</i> mutagenesis followed by genomic analysis of a resistant variant. The compound N’-[(E)-(5-methoxy-1H-indol-3-yl)methylidene]furan-2-carbohydrazide showed minimal inhibitory concentration (MIC) of 0.4412 μM for the reference strain <i>M. tuberculosis</i> H37Rv. An H37Rv clone resistant to elevated (4 × MIC) concentration of this compound recovered on a solid medium was further analyzed by whole genome sequencing and bioinformatics tools. A non-synonymous mutation was detected in the <i>Rv3755c</i> gene at position <i>302A&gt;G</i> (codon <i>101H&gt;R</i>, <i>CAC-CGC</i>). The gene–gene interaction analysis showed that this gene belongs to a network that also includes several ABC transporter genes. The identified mutation in <i>Rv3755c</i> may be associated with bacterial adaptation to the selective pressure of the studied aroylhydrazone derivative and reflect a non-specific drug tolerance mechanism. The conserved <i>M. tuberculosis</i> protein Rv3755c, whose function is unknown, may be related to the ABC transporter efflux system.</p>

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Adaptation of Mycobacterium tuberculosis to a New Aroylhydrazone Derivative In Vitro and Possible Role of Rv3755c Gene

  • 期刊论文

  • 发表日期：

    2025年8月1日

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  • I. V. Mokrousov,
  • V. Angelova,
  • S. Dimitrov,
  • S. A. Chekrygin,
  • V. Valcheva

摘要

We evaluated the response of Mycobacterium tuberculosis to exposure to a new aroylhydrazone derivative using the in vitro mutagenesis followed by genomic analysis of a resistant variant. The compound N’-[(E)-(5-methoxy-1H-indol-3-yl)methylidene]furan-2-carbohydrazide showed minimal inhibitory concentration (MIC) of 0.4412 μM for the reference strain M. tuberculosis H37Rv. An H37Rv clone resistant to elevated (4 × MIC) concentration of this compound recovered on a solid medium was further analyzed by whole genome sequencing and bioinformatics tools. A non-synonymous mutation was detected in the Rv3755c gene at position 302A>G (codon 101H>R, CAC-CGC). The gene–gene interaction analysis showed that this gene belongs to a network that also includes several ABC transporter genes. The identified mutation in Rv3755c may be associated with bacterial adaptation to the selective pressure of the studied aroylhydrazone derivative and reflect a non-specific drug tolerance mechanism. The conserved M. tuberculosis protein Rv3755c, whose function is unknown, may be related to the ABC transporter efflux system.