The Spermidine Synthase Gene as a Reporter of Transcription Inhibition in Escherichia coli

Izzi, Anton R.; Chernyshova, Alisa P.; Zhitlov, Mikhail Y.; Rudenko, Alexander Yu.; Ozhiganov, Ratislav M.; Ikhalaynen, Yury A.; Volynkina, Inna A.; Dorofeeva, Lubov V.; Tashlitsky, Vadim N.; Rodin, Igor A.; Evtushenko, Lyudmila I.; Alferova, Vera A.; Sergiev, Petr V.; Dontsova, Olga A.; Lukianov, Dmitrii A.

doi:10.3390/ijms27114829

This is an early access version, the complete PDF, HTML, and XML versions will be available soon.

Open AccessArticle

The Spermidine Synthase Gene as a Reporter of Transcription Inhibition in Escherichia coli

by

Anton R. Izzi

^1,2,3,

Alisa P. Chernyshova

^1,4,5,

Mikhail Y. Zhitlov

^3,4

,

Alexander Yu. Rudenko

³

,

Ratislav M. Ozhiganov

^3,5

,

Yury A. Ikhalaynen

⁵

,

Inna A. Volynkina

^1,5

,

Lubov V. Dorofeeva

⁶,

Vadim N. Tashlitsky

⁵

,

Igor A. Rodin

⁵,

Lyudmila I. Evtushenko

⁶,

Vera A. Alferova

^3,4

,

Petr V. Sergiev

^1,3,5,

Olga A. Dontsova

^1,4,5 and

Dmitrii A. Lukianov

^1,2,5,*

¹

Center for Bio- and Medical Technologies, 121205 Moscow, Russia

²

Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119234 Moscow, Russia

³

³ Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119234 Moscow, Russia

⁴

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia

⁵

Department of Chemistry, Lomonosov Moscow State University, 119234 Moscow, Russia

⁶

All-Russian Collection of Microorganisms (VKM), Pushchino Scientific Center for Biological Research, Russian Academy of Sciences, 142290 Pushchino, Russia

^*

Author to whom correspondence should be addressed.

Int. J. Mol. Sci. 2026, 27(11), 4829; https://doi.org/10.3390/ijms27114829

Submission received: 17 April 2026 / Revised: 8 May 2026 / Accepted: 21 May 2026 / Published: 27 May 2026

(This article belongs to the Special Issue 25th Anniversary of IJMS: Updates and Advances in Molecular Informatics)

Download Review Reports Versions Notes

Abstract

Antimicrobial resistance is a major threat to modern society and healthcare, as it severely compromises the efficacy of standard antibiotic treatments. To meet the ever-increasing demand for novel antimicrobial drugs, it is crucial to develop new strategies for screening antimicrobial compounds and improve existing high-throughput techniques. Reporter systems that employ specific genetic markers are powerful tools not only for detecting antimicrobial activity of the substance being studied, but also for identifying the potential mechanism of its action. Among other metabolic pathways, RNA biosynthesis machinery is considered a promising molecular target as it remains underutilized in current antimicrobial therapy and therefore is rarely exposed to drug pressure. However, there is no suitable biomarker for identifying compounds that inhibit the transcription in Gram-negative bacteria. Combining bioinformatic search and RT-qPCR experimental validation, we have established the overexpression of the spermidine synthase gene (speE) as a biomarker associated with impaired transcription in Escherichia coli. Monitoring the expression level of speE in antibiotic-treated cells enables reliable detection of compounds that inhibit bacterial RNA-polymerase, such as rifampicin and fidaxomicin. Moreover, our screening system was successfully applied in practice to analyze chromatography fractions from fermentation broth of antibiotic producers, with compounds of the rifamycin family being identified as hits and isolated. The proposed method has the potential to be used in sequential screening procedures to reveal active antimicrobial compounds that inhibit bacterial transcription process, giving the world novel antimicrobials with minimal risk of resistance development.

Keywords: antibiotics; mechanism of action; transcriptional inhibitors

Share and Cite

MDPI and ACS Style

Izzi, A.R.; Chernyshova, A.P.; Zhitlov, M.Y.; Rudenko, A.Y.; Ozhiganov, R.M.; Ikhalaynen, Y.A.; Volynkina, I.A.; Dorofeeva, L.V.; Tashlitsky, V.N.; Rodin, I.A.; et al. The Spermidine Synthase Gene as a Reporter of Transcription Inhibition in Escherichia coli. Int. J. Mol. Sci. 2026, 27, 4829. https://doi.org/10.3390/ijms27114829

AMA Style

Izzi AR, Chernyshova AP, Zhitlov MY, Rudenko AY, Ozhiganov RM, Ikhalaynen YA, Volynkina IA, Dorofeeva LV, Tashlitsky VN, Rodin IA, et al. The Spermidine Synthase Gene as a Reporter of Transcription Inhibition in Escherichia coli. International Journal of Molecular Sciences. 2026; 27(11):4829. https://doi.org/10.3390/ijms27114829

Chicago/Turabian Style

Izzi, Anton R., Alisa P. Chernyshova, Mikhail Y. Zhitlov, Alexander Yu. Rudenko, Ratislav M. Ozhiganov, Yury A. Ikhalaynen, Inna A. Volynkina, Lubov V. Dorofeeva, Vadim N. Tashlitsky, Igor A. Rodin, and et al. 2026. "The Spermidine Synthase Gene as a Reporter of Transcription Inhibition in Escherichia coli" International Journal of Molecular Sciences 27, no. 11: 4829. https://doi.org/10.3390/ijms27114829

APA Style

Izzi, A. R., Chernyshova, A. P., Zhitlov, M. Y., Rudenko, A. Y., Ozhiganov, R. M., Ikhalaynen, Y. A., Volynkina, I. A., Dorofeeva, L. V., Tashlitsky, V. N., Rodin, I. A., Evtushenko, L. I., Alferova, V. A., Sergiev, P. V., Dontsova, O. A., & Lukianov, D. A. (2026). The Spermidine Synthase Gene as a Reporter of Transcription Inhibition in Escherichia coli. International Journal of Molecular Sciences, 27(11), 4829. https://doi.org/10.3390/ijms27114829

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Menu

The Spermidine Synthase Gene as a Reporter of Transcription Inhibition in Escherichia coli

Abstract

Share and Cite

Article Metrics

Article Access Statistics

Further Information

Guidelines

MDPI Initiatives

Follow MDPI