Role of Small RNAs in Regulating Virulence Gene Expression in Salmonella Typhimurium and Pseudomonas aeruginosa: A Comparative Review

Authors

  • Abdul Ahad Mehboob Department of Pathology, National Laboratory & Testing Centre, Lahore, Punjab, Pakistan.
  • Faiqa Shakeel Faculty of Engineering and Science (FES), University of Greenwich, England, UK.
  • Hasnain Sajjad Department of Microbiology, The Islamia University of Bahawalpur, Punjab, Pakistan.
  • Anam Munir Institute of Microbiology, University of Agriculture, Faisalabad, Punjab, Pakistan.
  • Faiqa Tabassum Institute of Microbiology, University of Agriculture, Faisalabad, Punjab, Pakistan.
  • Urooj Fatima Department of Microbiology and Molecular Genetics, University of Okara, Punjab, Pakistan.

DOI:

https://doi.org/10.70749/ijbr.v3i9.2334

Keywords:

Small RNAs, Salmonella Typhimurium, Pseudomonas Aeruginosa, Virulence Regulation, Post-transcriptional Control, Antivirulence Therapies, RNA Chaperones, Bacterial Pathogenesis.

Abstract

In Gram-negative pathogens, small RNAs (sRNAs) play a crucial role as post-transcriptional regulators, coordinating the expression of virulence genes essential to pathogenesis. The function of sRNAs in Salmonella Typhimurium and Pseudomonas aeruginosa, model organisms for bacterial virulence research because of their unique ecological niches and intricate pathogenicity, is examined in this review. sRNAs govern quorum sensing, biofilm formation, and antibiotic resistance in Pseudomonas and Type III Secretion Systems (T3SS), motility, and stress responses in Salmonella. We highlight the function of RNA chaperones such as Hfq by comparing common and distinct sRNA-mediated regulatory mechanisms. RNA-seq and CRISPRi are two experimental methods that have improved the discovery and functional characterization of sRNA. With the potential to create synthetic sRNA mimics, antisense oligonucleotides, and vaccines, sRNAs provide new antivirulence targets for therapeutic use. Regulatory redundancy and context-dependent expression are obstacles that call for integrative multi-omics and systems biology methodologies. This review provides information on the therapeutic and biotechnological potential of sRNAs in the fight against infections by highlighting them as important regulators of bacterial pathogenesis.

Downloads

Download data is not yet available.

References

1. Morens, D. M., & Fauci, A. S. (2013). Emerging infectious diseases: Threats to human health and global stability. PLoS Pathogens, 9(7), e1003467.

https://doi.org/10.1371/journal.ppat.1003467

2. Scallan, E., Hoekstra, R. M., Angulo, F. J., Tauxe, R. V., Widdowson, M., Roy, S. L., Jones, J. L., & Griffin, P. M. (2011). Foodborne illness acquired in the United States—Major pathogens. Emerging Infectious Diseases, 17(1), 7-15.

https://doi.org/10.3201/eid1701.09-1101p1

3. Finlay, B. B., & Falkow, S. (1997). Common themes in microbial pathogenicity revisited. Microbiology and Molecular Biology Reviews, 61(2), 136-169.

https://doi.org/10.1128/mmbr.61.2.136-169.1997

4. Bobrovskyy, M., & Vanderpool, C. K. (2013). Regulation of bacterial metabolism by small RNAs using diverse mechanisms. Annual Review of Genetics, 47(1), 209-232.

https://doi.org/10.1146/annurev-genet-111212-133445

5. Papenfort, K., & Vogel, J. (2010). Regulatory RNA in bacterial pathogens. Cell Host & Microbe, 8(1), 116-127.

https://doi.org/10.1016/j.chom.2010.06.008

6. Vogel, J., & Luisi, B. F. (2011). Hfq and its constellation of RNA. Nature Reviews Microbiology, 9(8), 578-589.

https://doi.org/10.1038/nrmicro2615

7. Papenfort, K., & Vanderpool, C. K. (2015). Target activation by regulatory RNAs in bacteria. FEMS Microbiology Reviews, 39(3), 362-378.

https://doi.org/10.1093/femsre/fuv016

8. Sia, C. M., Pearson, J. S., Howden, B. P., Williamson, D. A., & Ingle, D. J. (2025). Salmonella pathogenicity islands in the genomic era. Trends in Microbiology, 33(7), 752-764.

https://doi.org/10.1016/j.tim.2025.02.007

9. Abdulla, S. Z., Kim, K., Azam, M. S., Golubeva, Y. A., Cakar, F., Slauch, J. M., & Vanderpool, C. K. (2022). Small RNAs Activate Salmonella Pathogenicity Island 1 by Modulating mRNA Stability through the hilD mRNA 3′ Untranslated Region.

https://doi.org/10.1101/2022.09.07.507058

10. Leimkühler, S., & Iobbi-Nivol, C. (2015). Bacterial molybdoenzymes: Old enzymes for new purposes. FEMS Microbiology Reviews, 40(1), 1-18.

https://doi.org/10.1093/femsre/fuv043

11. Monchy, S., Sanciu, G., Jobard, M., Rasconi, S., Gerphagnon, M., Chabé, M., Cian, A., Meloni, D., Niquil, N., Christaki, U., Viscogliosi, E., & Sime‐Ngando, T. (2011). Exploring and quantifying fungal diversity in freshwater lake ecosystems using rDNA cloning/sequencing and SSU tag pyrosequencing. Environmental Microbiology, 13(6), 1433-1453.

https://doi.org/10.1111/j.1462-2920.2011.02444.x

12. Savage, A. F., & Jude, B. A. (2014). Starting small: Using microbiology to foster scientific literacy. Trends in Microbiology, 22(7), 365-367.

https://doi.org/10.1016/j.tim.2014.04.005

13. Rasko, D. A., & Sperandio, V. (2010). Anti-virulence strategies to combat bacteria-mediated disease. Nature Reviews Drug Discovery, 9(2), 117-128.

https://doi.org/10.1038/nrd3013

14. Alker, A. P., Juliano, J. J., & Meshnick, S. R. (2009). Plasmodium falciparum and Dihydrofolate reductase I164L mutations in Africa. Antimicrobial Agents and Chemotherapy, 53(4), 1722-1723.

https://doi.org/10.1128/aac.01427-08

15. Wilen, C. B., McMullen, A. R., & Burnham, C. D. (2015). Comparison of sample preparation methods, instrumentation platforms, and contemporary commercial databases for identification of clinically relevant Mycobacteria by matrix-assisted laser desorption ionization–time of flight mass spectrometry. Journal of Clinical Microbiology, 53(7), 2308-2315.

https://doi.org/10.1128/jcm.00567-15

16. Pleguezuelos, O., Robinson, S., Stoloff, G. A., & Caparrós-Wanderley, W. (2012). Synthetic influenza vaccine (FLU-V) stimulates cell mediated immunity in a double-blind, randomised, placebo-controlled phase I trial. Vaccine, 30(31), 4655-4660.

https://doi.org/10.1016/j.vaccine.2012.04.089

17. Du Toit, A. (2015). Increasing diversity. Nature Reviews Microbiology, 13(5), 251-251.

https://doi.org/10.1038/nrmicro3482

18. Stower, H. (2014). Metabolically constrained regulatory networks. Nature Reviews Genetics, 15(2), 65-65.

https://doi.org/10.1038/nrg3665

19. Zhang, R., Vivanco, J. M., & Shen, Q. (2017). The unseen rhizosphere root–soil–microbe interactions for crop production. Current Opinion in Microbiology, 37, 8-14.

https://doi.org/10.1016/j.mib.2017.03.008

20. Papenfort, K., & Vogel, J. (2010). Regulatory RNA in bacterial pathogens. Cell Host & Microbe, 8(1), 116-127.

https://doi.org/10.1016/j.chom.2010.06.008

21. Abdulla, S. Z., Kim, K., Azam, M. S., Golubeva, Y. A., Cakar, F., Slauch, J. M., & Vanderpool, C. K. (2022). Small RNAs Activate Salmonella Pathogenicity Island 1 by Modulating mRNA Stability through the hilD mRNA 3′ Untranslated Region.

https://doi.org/10.1101/2022.09.07.507058

22. Vogel, J., & Luisi, B. F. (2011). Hfq and its constellation of RNA. Nature Reviews Microbiology, 9(8), 578-589.

https://doi.org/10.1038/nrmicro2615

23. Sukegawa, Y., Yamashita, A., & Yamamoto, M. (2011). The fission yeast stress-responsive MAPK pathway promotes meiosis via the phosphorylation of pol II CTD in response to environmental and feedback cues. PLoS Genetics, 7(12), e1002387.

https://doi.org/10.1371/journal.pgen.1002387

24. Pita, T., Feliciano, J. R., & Leitão, J. H. (2018). Small Noncoding regulatory RNAs from pseudomonas aeruginosa and Burkholderia cepacia complex. International Journal of Molecular Sciences, 19(12), 3759.

https://doi.org/10.3390/ijms19123759

25. Pita, T., Feliciano, J. R., & Leitão, J. H. (2018). Small Noncoding regulatory RNAs from pseudomonas aeruginosa and Burkholderia cepacia complex. International Journal of Molecular Sciences, 19(12), 3759.

https://doi.org/10.3390/ijms19123759

26. Linhartová, M., Bučinská, L., Halada, P., Ječmen, T., Šetlík, J., Komenda, J., & Sobotka, R. (2014). Accumulation of the Type IV prepilin triggers degradation of SECY and YIDC and inhibits synthesis of Photosystem II proteins in the cyanobacterium S ynechocystis PCC 6803. Molecular Microbiology, 93(6), 1207-1223.

https://doi.org/10.1111/mmi.12730

27. Hu, Y., & Holden, J. F. (2006). Citric acid cycle in the Hyperthermophilic Archaeon Pyrobaculum islandicum grown Autotrophically, Heterotrophically, and Mixotrophically with acetate. Journal of Bacteriology, 188(12), 4350-4355.

https://doi.org/10.1128/jb.00138-06

28. El Qaidi, S., & Plumbridge, J. (2008). Switching control of expression of ptsG from the Mlc Regulon to the NagC Regulon. Journal of Bacteriology, 190(16), 5733-5733.

https://doi.org/10.1128/jb.00857-08

29. Garcia-Mazcorro, J. F. (2013). Testing evolutionary models to explain the process of nucleotide substitution in gut bacterial 16S rRNA gene sequences. FEMS Microbiology Letters, 346(2), 97-104.

https://doi.org/10.1111/1574-6968.12207

30. Lennon, J. T. (2011). Replication, lies and lesser‐known truths regarding experimental design in environmental microbiology. Environmental Microbiology, 13(6), 1383-1386.

https://doi.org/10.1111/j.1462-2920.2011.02445.x

31. Miller, C. L., Romero, M., Karna, S. L., Chen, T., Heeb, S., & Leung, K. P. (2016). RsmW, pseudomonas aeruginosa small non-coding rsma-binding RNA upregulated in biofilm versus planktonic growth conditions. BMC Microbiology, 16(1).

https://doi.org/10.1186/s12866-016-0771-y

32. Reinhart, A. A., Powell, D. A., Nguyen, A. T., O'Neill, M., Djapgne, L., Wilks, A., Ernst, R. K., & Oglesby-Sherrouse, A. G. (2015). The prrF -encoded small regulatory RNAs are required for iron homeostasis and virulence of pseudomonas aeruginosa. Infection and Immunity, 83(3), 863-875.

https://doi.org/10.1128/iai.02707-14

33. Zhao, X., Zou, X., Li, Q., Cai, X., Li, L., Wang, J., Wang, Y., Fang, C., Xu, F., Huang, Y., Chen, B., Tang, J., & Wang, H. (2018). Total flavones of fermentation broth by Co-culture of Coprinus comatus and Morchella esculenta induces an anti-inflammatory effect on LPS-stimulated RAW264.7 macrophages cells via the MAPK signaling pathway. Microbial Pathogenesis, 125, 431-437.

https://doi.org/10.1016/j.micpath.2018.10.008

34. Linhartová, M., Bučinská, L., Halada, P., Ječmen, T., Šetlík, J., Komenda, J., & Sobotka, R. (2014). Accumulation of the Type IV prepilin triggers degradation of SECY and YIDC and inhibits synthesis of Photosystem II proteins in the cyanobacterium S ynechocystis PCC 6803. Molecular Microbiology, 93(6), 1207-1223.

https://doi.org/10.1111/mmi.12730

35. Liu, Z., Xu, Z., Chen, S., Huang, J., Li, T., Duan, C., Zhang, L., & Xu, Z. (2022). CzcR is essential for swimming motility in pseudomonas aeruginosa during zinc stress. Microbiology Spectrum, 10(6).

https://doi.org/10.1128/spectrum.02846-22

36. Zhao, X., Zou, X., Li, Q., Cai, X., Li, L., Wang, J., Wang, Y., Fang, C., Xu, F., Huang, Y., Chen, B., Tang, J., & Wang, H. (2018). Total flavones of fermentation broth by Co-culture of Coprinus comatus and Morchella esculenta induces an anti-inflammatory effect on LPS-stimulated RAW264.7 macrophages cells via the MAPK signaling pathway. Microbial Pathogenesis, 125, 431-437.

https://doi.org/10.1016/j.micpath.2018.10.008

37. Møller, T., Franch, T., Højrup, P., Keene, D. R., Bächinger, H. P., Brennan, R. G., & Valentin-Hansen, P. (2002). Hfq. Molecular Cell, 9(1), 23-30.

https://doi.org/10.1016/s1097-2765(01)00436-1

38. Bobrovskyy, M., & Vanderpool, C. K. (2013). Regulation of bacterial metabolism by small RNAs using diverse mechanisms. Annual Review of Genetics, 47(1), 209-232.

https://doi.org/10.1146/annurev-genet-111212-133445

39. Soranzo, N., Bianconi, G., & Altafini, C. (2007). Comparing association network algorithms for reverse engineering of large-scale gene regulatory networks: Synthetic versus real data. Bioinformatics, 23(13), 1640-1647.

https://doi.org/10.1093/bioinformatics/btm163

40. Sokoloski, J. E., & Bevilacqua, P. C. (2012). Analysis of RNA folding and ligand binding by conventional and high-throughput calorimetry. Methods in Molecular Biology, 145-174.

https://doi.org/10.1007/978-1-61779-949-5_10

41. Good, L., & Nielsen, P. E. (1998). Antisense inhibition of gene expression in bacteria by PNA targeted to mRNA. Nature Biotechnology, 16(4), 355-358.

https://doi.org/10.1038/nbt0498-355

42. Philippon, A., Slama, P., Dény, P., & Labia, R. (2016). A structure-based classification of Class A β-lactamases, a broadly diverse family of enzymes. Clinical Microbiology Reviews, 29(1), 29-57.

https://doi.org/10.1128/cmr.00019-15

43. Zhang, R., Vivanco, J. M., & Shen, Q. (2017). The unseen rhizosphere root–soil–microbe interactions for crop production. Current Opinion in Microbiology, 37, 8-14.

https://doi.org/10.1016/j.mib.2017.03.008

44. Voulgari, E., Gartzonika, C., Vrioni, G., Politi, L., Priavali, E., Levidiotou-Stefanou, S., & Tsakris, A. (2014). The Balkan region: NDM-1-producing klebsiella pneumoniae ST11 clonal strain causing outbreaks in Greece. Journal of Antimicrobial Chemotherapy, 69(8), 2091-2097.

https://doi.org/10.1093/jac/dku105

45. Heinemann, M., & Zenobi, R. (2011). Single cell metabolomics. Current Opinion in Biotechnology, 22(1), 26-31.

https://doi.org/10.1016/j.copbio.2010.09.008

46. Merino-Ramos, T., Vázquez-Calvo, Á., Casas, J., Sobrino, F., Saiz, J., & Martín-Acebes, M. A. (2016). Modification of the host cell lipid metabolism induced by Hypolipidemic drugs targeting the acetyl coenzyme a Carboxylase impairs west Nile virus replication. Antimicrobial Agents and Chemotherapy, 60(1), 307-315.

https://doi.org/10.1128/aac.01578-15

47. Quartinello, F., Vajnhandl, S., Volmajer Valh, J., Farmer, T. J., Vončina, B., Lobnik, A., Herrero Acero, E., Pellis, A., & Guebitz, G. M. (2017). Synergistic chemo‐enzymatic hydrolysis of poly(ethylene terephthalate) from textile waste. Microbial Biotechnology, 10(6), 1376-1383.

https://doi.org/10.1111/1751-7915.12734

48. Pleguezuelos, O., Robinson, S., Stoloff, G. A., & Caparrós-Wanderley, W. (2012). Synthetic influenza vaccine (FLU-V) stimulates cell mediated immunity in a double-blind, randomised, placebo-controlled phase I trial. Vaccine, 30(31), 4655-4660.

https://doi.org/10.1016/j.vaccine.2012.04.089

49. Beare, P. A., Sandoz, K. M., Larson, C. L., Howe, D., Kronmiller, B., & Heinzen, R. A. (2014). Essential role for the response regulator PmrA in Coxiella burnetii type 4B secretion and colonization of mammalian host cells. Journal of Bacteriology, 196(11), 1925-1940.

https://doi.org/10.1128/jb.01532-14

50. Du Toit, A. (2015). Increasing diversity. Nature Reviews Microbiology, 13(5), 251-251.

https://doi.org/10.1038/nrmicro3482

51. Caswell, C. C., Oglesby-Sherrouse, A. G., & Murphy, E. R. (2014). Sibling rivalry: Related bacterial small RNAs and their redundant and non-redundant roles. Frontiers in Cellular and Infection Microbiology, 4.

https://doi.org/10.3389/fcimb.2014.00151

52. Chen, R., Weng, Y., Zhu, F., Jin, Y., Liu, C., Pan, X., Xia, B., Cheng, Z., Jin, S., & Wu, W. (2016). Polynucleotide phosphorylase regulates multiple virulence factors and the stabilities of small RNAs RsmY/Z in pseudomonas aeruginosa. Frontiers in Microbiology, 7.

https://doi.org/10.3389/fmicb.2016.00247

53. Stower, H. (2014). Metabolically constrained regulatory networks. Nature Reviews Genetics, 15(2), 65-65.

https://doi.org/10.1038/nrg3665

54. Good, L., & Nielsen, P. E. (1998). Antisense inhibition of gene expression in bacteria by PNA targeted to mRNA. Nature Biotechnology, 16(4), 355-358.

https://doi.org/10.1038/nbt0498-355

55. Mather, A. E. (2015). There's no place like home. Nature Reviews Microbiology, 13(6), 331-331.

https://doi.org/10.1038/nrmicro3497

56. Janssen, K. H., Diaz, M. R., Golden, M., Graham, J. W., Sanders, W., Wolfgang, M. C., & Yahr, T. L. (2018). Functional analyses of the RsmY and RsmZ small Noncoding regulatory RNAs in pseudomonas aeruginosa. Journal of Bacteriology, 200(11).

https://doi.org/10.1128/jb.00736-17

57. Łyżeń, R., Maitra, A., Milewska, K., Kochanowska-Łyżeń, M., Hernandez, V. J., & Szalewska-Pałasz, A. (2016). The dual role of DksA protein in the regulation ofEscherichia colipArgX promoter. Nucleic Acids Research, gkw912.

https://doi.org/10.1093/nar/gkw912

58. Becker, N. A., Schwab, T. L., Clark, K. J., & Maher, L. J. (2018). Bacterial gene control by DNA looping using engineered dimeric transcription activator like effector (TALE) proteins. Nucleic Acids Research, 46(5), 2690-2696.

https://doi.org/10.1093/nar/gky047

59. Chevrette, M. G., Aicheler, F., Kohlbacher, O., Currie, C. R., & Medema, M. H. (2017). Sandpuma: Ensemble predictions of nonribosomal peptide chemistry reveal biosynthetic diversity across Actinobacteria. Bioinformatics, 33(20), 3202-3210.

https://doi.org/10.1093/bioinformatics/btx400

60. Merino-Ramos, T., Vázquez-Calvo, Á., Casas, J., Sobrino, F., Saiz, J., & Martín-Acebes, M. A. (2016). Modification of the host cell lipid metabolism induced by Hypolipidemic drugs targeting the acetyl coenzyme a Carboxylase impairs west Nile virus replication. Antimicrobial Agents and Chemotherapy, 60(1), 307-315.

https://doi.org/10.1128/aac.01578-15

61. Wilen, C. B., McMullen, A. R., & Burnham, C. D. (2015). Comparison of sample preparation methods, instrumentation platforms, and contemporary commercial databases for identification of clinically relevant Mycobacteria by matrix-assisted laser desorption ionization–time of flight mass spectrometry. Journal of Clinical Microbiology, 53(7), 2308-2315.

https://doi.org/10.1128/jcm.00567-15

62. Koch, L. (2016). Genetic associations with a social science outcome. Nature Reviews Genetics, 17(7), 375-375.

https://doi.org/10.1038/nrg.2016.73

63. Zhu, J., Lolle, S., Tang, A., Guel, B., Kvitko, B., Cole, B., & Coaker, G. (2023). Single-cell profiling of arabidopsis leaves to pseudomonas syringae infection. Cell Reports, 42(7), 112676.

https://doi.org/10.1016/j.celrep.2023.112676

64. Grützner, J., Remes, B., Eisenhardt, K. M., Scheller, D., Kretz, J., Madhugiri, R., McIntosh, M., & Klug, G. (2021). Srna-mediated RNA processing regulates bacterial cell division. Nucleic Acids Research, 49(12), 7035-7052.

https://doi.org/10.1093/nar/gkab491

65. Mather, A. E. (2015). There's no place like home. Nature Reviews Microbiology, 13(6), 331-331.

https://doi.org/10.1038/nrmicro3497

66. Gao, F. (2010). Context-dependent functions of specific microRNAs in neuronal development. Neural Development, 5(1).

https://doi.org/10.1186/1749-8104-5-25

67. Seneviratne, C. J., Suriyanarayanan, T., Widyarman, A. S., Lee, L. S., Lau, M., Ching, J., Delaney, C., & Ramage, G. (2020). Multi-omics tools for studying microbial biofilms: Current perspectives and future directions. Critical Reviews in Microbiology, 46(6), 759-778.

https://doi.org/10.1080/1040841x.2020.1828817

68. Lee, F. C., & Ule, J. (2018). Advances in CLIP technologies for studies of Protein-RNA interactions. Molecular Cell, 69(3), 354-369.

https://doi.org/10.1016/j.molcel.2018.01.005

Downloads

Published

2025-09-30

How to Cite

Mehboob, A. A., Shakeel, F., Sajjad, H., Munir, A., Tabassum, F., & Fatima, U. (2025). Role of Small RNAs in Regulating Virulence Gene Expression in Salmonella Typhimurium and Pseudomonas aeruginosa: A Comparative Review. Indus Journal of Bioscience Research, 3(9), 256-264. https://doi.org/10.70749/ijbr.v3i9.2334