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Front. Microbiol., 06 October 2023
Sec. Microbial Physiology and Metabolism
Volume 14 - 2023 |

Editorial: Role of transcription factors and sigma factors in bacterial stress physiology

  • 1Instituto de Investigaciones en Matemáticas Aplicadas y en Sistemas, Universidad Nacional Autónoma de México, Unidad Académica del Estado de Yucatán, Mérida, Mexico
  • 2Department of Biology, McMaster University, Hamilton, ON, Canada
  • 3Metabolic Engineering and Fermentation Science Group, Department of Food Science, University of Wisconsin-Madison, Madison, WI, United States

Microorganisms are equipped with genetic information in their DNA essential for duplication to survival in the environment. Transcription is the first committed step in gene expression where DNA is copied into RNA which is then translated into proteins to control various biological processes (Mejía-Almonte et al., 2020). To control the flow of this genetic information, microbial genomes encode a wide diversity of transcriptional regulators that interact and compete with core RNA polymerase to transcribe gene expression to cope with changing environmental conditions (Seshasayee et al., 2011; Browning et al., 2019). The number of these regulators can vary from one microorganism to another depending on their lifestyle and fluctuations in external and internal environmental factors, such as temperature pH, salinity, nutrient supply, and antibiosis. Under ambient conditions, most genes required for metabolic process are controlled by the housekeeping sigma factor, RpoD or σ70. However, microorganisms also employ alternative sigma factors such as RpoN or σ54 for nitrogen metabolism, RpoH or σ32 for heat stress, RpoS for stationary phase stress, and RpoE or σ24 to regulate responses to oxidative stress, and other extra-cytoplasmic stresses (Paget and Helmann, 2003). Transcription factors (TFs) belonging to diverse families, such as MarR family, GntR family, TetR family, and CRP/FNR family control expression of antibiotics resistance, pathogenicity, biofilm, and other numerous biological processes ( These sigma factors and transcription factors differ from each other due to their distinct protein domains involved in interacting with specific binding sites on DNA, called promoters and transcription factor binding sites (repressors and activators sites), respectively (Perez-Rueda et al., 2018). Multiple interacting partners and cross-talk among different regulators can interplay in sensing and controlling the transcription of genes under changing environmental conditions (Rai et al., 2018; Taylor et al., 2022). Therefore, molecular analysis of the role and regulation of transcriptional regulators is central to understand microbial process like stress adaptation, drug resistance, virulence, and disease progression, among others (Schellhorn, 2014; Roncarati et al., 2022).

This Research Topic focuses on the role and regulation of sigma factors and transcription factors governing initiation of gene expression under various physiological and stress conditions. For instance, Lovelace et al. compared the capacity of two common Salmonella enterica strains, 14028s and LT2 (strain DM10000) to opportunistically colonize the leaf apoplast of two model plant hosts Arabidopsis thaliana and Nicotiana benthamiana during disease. In this regard, the authors identified rpoS (sigma S)-dependent alterations in the utilization of L-malic acid, an abundant carbon source in N. benthamiana apoplastic wash fluid. In addition, data were found to be consistent with higher relative basal values of reactive oxygen species (ROS) in N. benthamiana leaves than in A. thaliana leaves. Finally, the study indicates that the conducive environment generated by pathogen modulation of the apoplast niche can vary from hosts to host even with a common disease-compatible pathogen.

Bensig et al. identified the gene srlA (stress resistance locus A) required for growth on solid media with increased NaCl concentrations in the nitrogen-fixing facultative endosymbiont Sinorhizobium (Ensifer) meliloti. The encoded protein carries a predicted thioredoxin fold and deletion of the gene also results in increased sensitivity to hydrogen peroxide and cumene hydroperoxide. A deletion mutant yields phenotypic revertants on high salt medium and genome sequencing revealed that all revertants carry a mutation in genes homologous to either cenK or cenR. srlA promoter activity is abolished in these revertant host backgrounds and in a strain carrying a deletion in cenK. The authors also observed that the srlA promoter is autoregulated, displaying low activity in a wildtype (wt) host background and high activity in the srl deletion mutant background. The srlA promoter includes a conserved inverted repeat directly upstream of the predicted −35 subsequence. Finally, these results document the first identified CenK–CenR regulon member in S. meliloti and demonstrate this two-component regulatory system and gene srlA influences cellular growth and persistence under certain stress-inducing conditions.

Costa et al. reconstructed a Gene regulatory network (GRN) in the pathogen Staphylococcus aureus. They considered literature-based and comparative genomics approaches to reconstruct the GRN of the high biofilm-producing strain Bmb9393, belonging to one of the highly disseminating successful clones, the Brazilian epidemic clone. In addition, the authors analyzed transcriptomes available in the literature to construct a set of genes differentially expressed in the biofilm, covering different stages of the biofilms and genetic backgrounds of the strains. In total, the GRN comprises 1,803 regulatory interactions between 64 transcription factors and the non-redundant set of 1,151 target genes with the inclusion of 19 new regulons compared to the S. aureus strain N315 transcriptional regulatory network published in 2011. Finally, the mapping of the set of genes with altered expression in the biofilm in the Bmb9393 gene regulatory network would help to depict how different growth modes can alter the regulatory systems. The data revealed 45 transcription factors and 876 shared target genes. Thus, the gene regulatory network model provided represents the most up-to-date model for S. aureus, and the set of genes altered in the biofilm provides a global view of their influence on biofilm formation from distinct experimental perspectives and different strain backgrounds.

Finally, Hołówka et al. analyzed the Nucleoid-associated proteins (NAPs) associated to the organization of bacterial chromatin and regulating gene expression. In particular, the authors used super-resolution microscopy, to perform a comprehensive analysis of the roles of HupB and mIHF in chromosome organization in Mycobacterium smegmatis. They described that HupB is a structural agent that maintains chromosome integrity on a local scale, and that the lack of this protein alters chromosome morphology. In contrast, mIHF is a highly dynamic protein that binds DNA only transiently, exhibits susceptibility to the chromosomal DNA topology changes and whose depletion leads to the growth arrest of tubercle bacilli. Additionally, the depletion of Mycobacterium smegmatis integration host factor (msIHF) leads to chromosome shrinkage and replication inhibition.

Author contributions

EP-R: Writing—original draft, Writing—review and editing. SK: Writing—original draft, Writing—review and editing. HS: Writing—original draft, Writing—review and editing.


EP-R was supported by Dirección General de Asuntos del Personal Académico-Universidad Nacional Autónoma de México (IN-220523) and CONAHCYT (320012).

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

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Browning, D. F., Butala, M., and Busby, S. J. W. (2019). Bacterial transcription factors: regulation by pick “N” Mix. J. Mol. Biol. 431, 4067–4077. doi: 10.1016/j.jmb.2019.04.011

PubMed Abstract | CrossRef Full Text | Google Scholar

Mejía-Almonte, C., Busby, S. J. W., Wade, J. T., van Helden, J., Arkin, A. P., Stormo, G. D., et al. (2020). Redefining fundamental concepts of transcription initiation in bacteria. Nat. Rev. Genet. 21, 699–714. doi: 10.1038/s41576-020-0254-8

PubMed Abstract | CrossRef Full Text | Google Scholar

Paget, M. S., and Helmann, J. D. (2003). The sigma70 family of sigma factors. Genome Biol. 4, 203. doi: 10.1186/gb-2003-4-1-203

PubMed Abstract | CrossRef Full Text | Google Scholar

Perez-Rueda, E., Hernandez-Guerrero, R., Martinez-Nuñez, M. A., Armenta-Medina, D., Sanchez, I., and Ibarra, J. A. (2018). Abundance, diversity and domain architecture variability in prokaryotic DNA-binding transcription factors. PLoS ONE. 13, e0195332. doi: 10.1371/journal.pone.0195332

PubMed Abstract | CrossRef Full Text | Google Scholar

Rai, A. K., Singh, S., Dwivedi, S. K., Srivastava, A., Pandey, P., Kumar, S., et al. (2018). Catalase expression in Azospirillum brasilense Sp7 is regulated by a network consisting of OxyR and two RpoH paralogs and including an RpoE1 → RpoH5 regulatory cascade. Appl. Environ. Microbiol. 84, e01787–e01718. doi: 10.1128/AEM.01787-18

PubMed Abstract | CrossRef Full Text | Google Scholar

Roncarati, D., Scarlato, V., and Vannini, A. (2022). Targeting of regulators as a promising approach in the search for novel antimicrobial agents. Microorganisms. 10, 185. doi: 10.3390/microorganisms10010185

PubMed Abstract | CrossRef Full Text | Google Scholar

Schellhorn, H. E. (2014). Elucidating the function of the RpoS regulon. Fut. Microbiol. 9, 497–507. doi: 10.2217/fmb.14.9

PubMed Abstract | CrossRef Full Text | Google Scholar

Seshasayee, A. S., Sivaraman, K., and Luscombe, N. M. (2011). An overview of prokaryotic transcription factors: a summary of function and occurrence in bacterial genomes. Subcell. Biochem. 52, 7–23. doi: 10.1007/978-90-481-9069-0_2

PubMed Abstract | CrossRef Full Text | Google Scholar

Taylor, T. B., Shepherd, M. J., Jackson, R. W., and Silby, M. W. (2022). Natural selection on crosstalk between gene regulatory networks facilitates bacterial adaptation to novel environments. Curr. Opin. Microbiol. 67, 102140. doi: 10.1016/j.mib.2022.02.002

PubMed Abstract | CrossRef Full Text | Google Scholar

Keywords: microbial physiology, environmental stress response, gene expression, alternative sigma factors, transcription factors (TFs)

Citation: Perez-Rueda E, Schellhorn HE and Kumar S (2023) Editorial: Role of transcription factors and sigma factors in bacterial stress physiology. Front. Microbiol. 14:1291172. doi: 10.3389/fmicb.2023.1291172

Received: 08 September 2023; Accepted: 25 September 2023;
Published: 06 October 2023.

Edited and reviewed by: Biswarup Mukhopadhyay, Virginia Tech, United States

Copyright © 2023 Perez-Rueda, Schellhorn and Kumar. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Ernesto Perez-Rueda,; Herb E. Schellhorn,; Santosh Kumar,