MICROBIAL SIGNALING NETWORKS: BRIDGING CELLULAR COMMUNICATION WITH APPLICATIONS IN HEALTH, AGRICULTURE, AND BIOTECHNOLOGY
Keywords:
Quorum sensing, autoinducers, microbial signaling, cellular microenvironment, hostmicrobe interaction, biotechnology, regenerative medicine, sustainable agricultureAbstract
Microorganisms utilize intricate chemical signaling mechanisms to communicate both within and across species, influencing a wide range of physiological behaviors and ecological interactions. Among these mechanisms, quorum sensing stands out as a pivotal strategy that bacteria employ to detect population density and coordinate gene expression in a collective manner. These signaling systems are mediated by autoinducers and other secondary metabolites, such as peptides, fatty acids, terpenoids, and alkaloids. These molecules not only facilitate intra- and inter-species communication but also enable inter-kingdom interactions with host organisms, modulating host immune responses, gut health, and even cell fate decisions. Importantly, the understanding and manipulation of these microbial signals have opened new frontiers in biotechnology, particularly in the areas of regenerative medicine, sustainable agriculture, and antimicrobial therapy. This review provides a comprehensive overview of microbial signaling molecules, the evolution of cellcell communication, the role of the cellular microenvironment, and emerging strategies for engineering functional cellular responses. By elucidating the pathways and applications of microbial signaling, we propose innovative approaches to convert non-functional or damaged cells into functional units, benefiting both human health and environmental sustainability.
References
[1] Yajima, A. (2016). Recent advances in the chemistry and chemical biology of quorum-sensing
pheromones and microbial hormones. Studies in Natural Products Chemistry, 47, 331–355.
https://doi.org/10.1016/B978-0-444-63603-4.00010-3
[2] Abebe, G. M. (2021). Oral biofilm and its impact on oral health, psychological and social
interaction. Int. J. Oral Dent. Health, 7, 127–137. https://doi.org/10.23937/2469-
5734/1510127
[3] Hughes, D. T., & Sperandio, V. (2008). Inter-kingdom signalling: communication between
bacteria and their hosts. Nature Reviews Microbiology, 6(2), 111–120.
https://doi.org/10.1038/nrmicro1836
[4] Balan, B., Dhaulaniya, A. S., Varma, D. A., Sodhi, K. K., Kumar, M., Tiwari, M., & Singh, D.
K. (2021). Microbial biofilm ecology, in silico study of quorum sensing receptor-ligand
interactions and biofilm mediated bioremediation. Archives of Microbiology, 203, 13–30.
https://doi.org/10.1007/s00203-020-02012-9
[5] Camilli, A., & Bassler, B. L. (2006). Bacterial small-molecule signaling pathways. Science
(New York, N.Y.), 311(5764), 1113–1116. https://doi.org/10.1126/science.1121357
https://doi.org/10.1126/science.112135
[6] Huang, S., Liu, X., Yang, W., Ma, L., Li, H., Liu, R., Qiu, J., & Li, Y. (2022). Insights into
Adaptive Mechanisms of Extreme Acidophiles Based on Quorum Sensing/QuenchingRelated Proteins. Msystems, 7(2), e01491-21. https://doi.org/10.1128/msystems.01491-21
[7] Groult, B., Bredin, P., & Lazar, C. S. (2022). Ecological processes differ in community
assembly of Archaea, Bacteria and Eukaryotes in a biogeographical survey of groundwater
habitats in the Quebec region (Canada). Environmental Microbiology, 24(12), 5898–5910.
https://doi.org/10.1111/1462-2920.16219
[8] Wang, Y., Huang, W., Han, Y., Huang, X., Wang, C., Ma, K., Kong, M., Jiang, N., & Pan, J.
(2022). Microbial diversity of archaeological ruins of Liangzhu City and its correlation with
environmental factors. International Biodeterioration & Biodegradation, 175, 105501.
https://doi.org/10.1016/j.ibiod.2022.105501
[9] Chamkhi, I., El Omari, N., Benali, T., & Bouyahya, A. (2020). Quorum sensing and plantbacteria interaction: role of quorum sensing in the rhizobacterial community colonization in
the rhizosphere. In Quorum Sensing: Microbial Rules of Life (pp. 139–153). ACS
Publications. https://doi.org/10.1021/bk-2020-1374.ch008
[10] Combarnous, Y., & Nguyen, T. M. D. (2020). Cell communications among microorganisms,
plants, and animals: origin, evolution, and interplays. International Journal of Molecular
Sciences, 21(21), 8052. https://doi.org/10.3390/ijms21218052
[11] Rosset, S. L., Oakley, C. A., Ferrier-Pagès, C., Suggett, D. J., Weis, V. M., & Davy, S. K.
(2021). The molecular language of the cnidarian–dinoflagellate symbiosis. Trends in
Microbiology, 29(4), 320–333. https://doi.org/10.1016/j.tim.2020.08.005
[12] Patrad, E., Khalighfard, S., Amiriani, T., Khori, V., & Alizadeh, A. M. (2022). Molecular
mechanisms underlying the action of carcinogens in gastric cancer with a glimpse into
targeted therapy. Cellular Oncology, 1–45. https://doi.org/10.1007/s13402-022-00715-3
[13] Tyson, J., Bundy, K., Roach, C., Douglas, H., Ventura, V., Segars, M. F., Schwartz, O., &
Simpson, C. L. (2020). Mechanisms of the osteogenic switch of smooth muscle cells in
vascular calcification: WNT signaling, BMPs, mechanotransduction, and EndMT.
Bioengineering, 7(3), 88. https://doi.org/10.3390/bioengineering7030088
[14] AlMusawi, S., Ahmed, M., & Nateri, A. S. (2021). Understanding cell‐cell communication
and signaling in the colorectal cancer microenvironment. Clinical and Translational
Medicine, 11(2), e308. https://doi.org/10.1002/ctm2.308
[15] Shin, Y., Chane, A., Jung, M., & Lee, Y. (2021). Recent advances in understanding the roles
of pectin as an active participant in plant signaling networks. Plants, 10(8), 1712.
https://doi.org/10.3390/plants10081712
[16] Wolf, S. (2022). Cell wall signaling in plant development and defense. Annual Review of
Plant Biology, 73, 323–353. https://doi.org/10.1146/annurev-arplant-102820-095312
[17] Davares, A. K. L., Arsene, M. M. J., Viktorovna, P. I., Vyacheslavovna, Y. N., Vladimirovna,
Z. A., Aleksandrovna, V. E., Nikolayevich, S. A., Nadezhda, S., Anatolievna, G. O., &
Nikolaevna, S. I. (2022). Quorum-Sensing Inhibitors from Probiotics as a Strategy to Combat
Bacterial Cell-to-Cell Communication Involved in Food Spoilage and Food Safety.
Fermentation, 8(12), 711. https://doi.org/10.3390/fermentation8120711
[18] Duddy, O. P., & Bassler, B. L. (2021). Quorum sensing across bacterial and viral domains.
PLoS Pathogens, 17(1), e1009074. https://doi.org/10.1371/journal.ppat.1009074
[19] Jin, T., Patel, S. J., & Van Lehn, R. C. (2021). Molecular simulations of lipid membrane
partitioning and translocation by bacterial quorum sensing modulators. Plos One, 16(2),
e0246187. https://doi.org/10.1371/journal.pone.0246187
[20] Brindhadevi, K., LewisOscar, F., Mylonakis, E., Shanmugam, S., Verma, T. N., &
Pugazhendhi, A. (2020). Biofilm and Quorum sensing mediated pathogenicity in
Pseudomonas aeruginosa. Process Biochemistry, 96, 49–57.
https://doi.org/10.1016/j.procbio.2020.06.001
[21] Zhou, L., Zhang, Y., Ge, Y., Zhu, X., & Pan, J. (2020). Regulatory mechanisms and promising
applications of quorum sensing-inhibiting agents in control of bacterial biofilm formation.
Frontiers in Microbiology, 11, 589640. https://doi.org/10.3389/fmicb.2020.589640
[22] Davies, D. G., Parsek, M. R., Pearson, J. P., Iglewski, B. H., Costerton, J. W., & Greenberg,
E. P. (1998). The involvement of cell-to-cell signals in the development of a bacterial biofilm.
Science (New York, N.Y.), 280(5361), 295–298.
https://doi.org/10.1126/science.280.5361.295 https://doi.org/10.1126/science.280.5361.295
[23] Wiesmann, C. L., Wang, N. R., Zhang, Y., Liu, Z., & Haney, C. H. (2022). Origins of
symbiosis: shared mechanisms underlying microbial pathogenesis, commensalism and
mutualism of plants and animals. FEMS Microbiology Reviews.
https://doi.org/10.1093/femsre/fuac048
[24] Nealson, K. H., Platt, T., & Hastings, J. W. (1970). Cellular control of the synthesis and activity of the bacterial luminescent system. Journal of Bacteriology, 104(1), 313–322.
https://doi.org/10.1128/jb.104.1.313-322.1970
[25] Pan, J., Zhou, J., Tang, X., Guo, Y., Zhao, Y., & Liu, S. (2023). Bacterial Communication
Coordinated Behaviors of Whole Communities to Cope with Environmental Changes.
Environmental Science & Technology. https://doi.org/10.1021/acs.est.2c05780
[26] Wang, S., Payne, G. F., & Bentley, W. E. (2020). Quorum sensing communication:
molecularly connecting cells, their neighbors, and even devices. Annual Review of Chemical
and Biomolecular Engineering, 11, 447–468. https://doi.org/10.1146/annurev-chembioeng-
101519-124728
[27] Wu, L., & Luo, Y. (2021). Bacterial quorum-sensing systems and their role in intestinal
bacteria-host crosstalk. Frontiers in Microbiology, 12, 611413.
https://doi.org/10.3389/fmicb.2021.611413
[28] Tang, M., Liao, S., Qu, J., Liu, Y., Han, S., Cai, Z., Fan, Y., Yang, L., Li, S., & Li, L. (2022).
Evaluating Bacterial Pathogenesis Using a Model of Human Airway Organoids Infected with
Pseudomonas aeruginosa Biofilms. Microbiology Spectrum, 10(6), e02408-22.
https://doi.org/10.1128/spectrum.02408-22
[29] Hwang, O.-J., & Back, K. (2022). Functional Characterization of Arylalkylamine NAcetyltransferase, a Pivotal Gene in Antioxidant Melatonin Biosynthesis from
Chlamydomonas reinhardtii. Antioxidants, 11(8), 1531.
https://doi.org/10.3390/antiox11081531
[30] Tang, Y., Chen, H., Lin, Z., Zhang, L., Upadhyay, A., Liao, C., Merkler, D. J., & Han, Q.
(2022). Evolutionary genomics analysis reveals gene expansion and functional diversity of
arylalkylamine N‐acetyltransferases in the Culicinae subfamily of mosquitoes. Insect
Science. https://doi.org/10.1111/1744-7917.13100
[31] Cui, F., Zhou, Z., & Zhou, H. S. (2020). Molecularly imprinted polymers and surface
imprinted polymers based electrochemical biosensor for infectious diseases. Sensors, 20(4),
996. https://doi.org/10.3390/s20040996
[32] Huang, J., Zhang, L., Wan, D., Zhou, L., Zheng, S., Lin, S., & Qiao, Y. (2021). Extracellular
matrix and its therapeutic potential for cancer treatment. Signal Transduction and Targeted
Therapy, 6(1), 153. https://doi.org/10.1038/s41392-021-00544-0
[33] Xiao, L., Sun, Y., Liao, L., & Su, X. (2023). Response of mesenchymal stem cells to surface
topography of scaffolds and the underlying mechanisms. Journal of Materials Chemistry B.
https://doi.org/10.1039/D2TB01875F
[34] Shao, Y., & Fu, J. (2014). Integrated micro/nanoengineered functional biomaterials for cell
mechanics and mechanobiology: a materials perspective. Advanced Materials, 26(10), 1494-
1533. https://doi.org/10.1002/adma.201304431
[35] Tanaka, M., Nakahata, M., Linke, P., & Kaufmann, S. (2020). Stimuli-responsive hydrogels
as a model of the dynamic cellular microenvironment. Polymer Journal, 52(8), 861–870.
https://doi.org/10.1038/s41428-020-0353-6
[36] Gross, S. M., Dane, M. A., Smith, R. L., Devlin, K. L., McLean, I. C., Derrick, D. S., Mills,
C. E., Subramanian, K., London, A. B., & Torre, D. (2022). A multi-omic analysis of
MCF10A cells provides a resource for integrative assessment of ligand-mediated molecular
and phenotypic responses. Communications Biology, 5(1), 1066.
https://doi.org/10.1038/s42003-022-03975-9
[37] Al Mamun, A., & Rahman, S. T. (2025). Microbial Signaling Networks: Bridging Cellular
Communication with Applications in Health, Agriculture, and Biotechnology. https://doi.org/
10.20944/preprints202504.1833.v1
[38] Lu, P., Takai, K., Weaver, V. M., & Werb, Z. (2011). Extracellular matrix degradation and
remodeling in development and disease. Cold Spring Harbor Perspectives in Biology, 3(12),
a005058. https://doi.org/10.1101/cshperspect.a005058
[39] Thomas, G. J., Hart, I. R., Speight, P. M., & Marshall, J. F. (2002). Binding of TGF-beta1
latency-associated peptide (LAP) to alpha(v)beta6 integrin modulates behaviour of
squamous carcinoma cells. British Journal of Cancer, 87(8), 859–867.
https://doi.org/10.1038/sj.bjc.6600545
[40] Lemmon, C. A., Chen, C. S., & Romer, L. H. (2009). Cell traction forces direct fibronectin
matrix assembly. Biophysical Journal, 96(2), 729–738.
https://doi.org/10.1016/j.bpj.2008.10.009
[41] Legant, W. R., Chen, C. S., & Vogel, V. (2012). Force-induced fibronectin assembly and
matrix remodeling in a 3D microtissue model of tissue morphogenesis. Integrative Biology :
Quantitative Biosciences from Nano to Macro, 4(10), 1164–1174.
https://doi.org/10.1039/c2ib20059g
[42] DeMali, K. A., Sun, X., & Bui, G. A. (2014). Force transmission at cell-cell and cell-matrix
adhesions. Biochemistry, 53(49), 7706–7717. https://doi.org/10.1021/bi501181p
[43] DuFort, C. C., Paszek, M. J., & Weaver, V. M. (2011). Balancing forces: architectural control
of mechanotransduction. Nature Reviews. Molecular Cell Biology, 12(5), 308–319.
https://doi.org/10.1038/nrm3112
[44] Elvevoll, E. O., James, D., Toppe, J., Gamarro, E. G., & Jensen, I.-J. (2022). Food Safety
Risks Posed by Heavy Metals and Persistent Organic Pollutants (POPs) related to
Consumption of Sea Cucumbers. Foods, 11(24), 3992.
https://doi.org/10.3390/foods11243992
[45] Xing, H., Lee, H., Luo, L., & Kyriakides, T. R. (2020). Extracellular matrix-derived
biomaterials in engineering cell function. Biotechnology Advances, 42, 107421.
https://doi.org/10.1016/j.biotechadv.2019.107421
[46] Dalton, C. J., & Lemmon, C. A. (2021). Fibronectin: Molecular structure, fibrillar structure
and mechanochemical signaling. Cells, 10(9), 2443. https://doi.org/10.3390/cells10092443
[47] Miller, A. E., Hu, P., & Barker, T. H. (2020). Feeling things out: bidirectional signaling of
the cell–ECM interface, implications in the mechanobiology of cell spreading, migration,
proliferation, and differentiation. Advanced Healthcare Materials, 9(8), 1901445.
https://doi.org/10.1002/adhm.201901445
[48] Virdi, J. K., & Pethe, P. (2021). Biomaterials regulate mechanosensors YAP/TAZ in stem cell
growth and differentiation. Tissue Engineering and Regenerative Medicine, 18(2), 199–215.
https://doi.org/10.1007/s13770-020-00301-4
[49] Lucke, M., Correa, M. G., & Levy, A. (2020). The role of secretion systems, effectors, and
secondary metabolites of beneficial rhizobacteria in interactions with plants and
microbes. Frontiers in Plant Science, 11, 589416. https://doi.org/10.3389/fpls.2020.589416
[50] Jamil, F., Mukhtar, H., Fouillaud, M., & Dufossé, L. (2022). Rhizosphere signaling: Insights
into plant–rhizomicrobiome interactions for sustainable agronomy. Microorganisms, 10(5),
899. https://doi.org/10.3390/microorganisms10050899
[51] Singh, S. K., Wu, X., Shao, C., & Zhang, H. (2022). Microbial enhancement of plant nutrient
acquisition. Stress Biology, 2(1), 3. https://doi.org/10.1007/s44154-021-00027-w
[52] Timofeeva, A. M., Galyamova, M. R., & Sedykh, S. E. (2023). Plant growth-promoting soil
bacteria: Nitrogen fixation, phosphate solubilization, siderophore production, and other
biological activities. Plants, 12(24), 4074. https://doi.org/10.3390/plants12244074
[53] Chaudhary, P., Agri, U., Chaudhary, A., Kumar, A., & Kumar, G. (2022). Endophytes and
their potential in biotic stress management and crop production. Frontiers in
microbiology, 13, 933017. https://doi.org/10.3389/fmicb.2022.933017
[54] Patra, D., & Mandal, S. (2022). Non-rhizobia are the alternative sustainable solution for
growth and development of the nonlegume plants. Biotechnology and Genetic Engineering
Reviews, 1–30. https://doi.org/10.1080/02648725.2022.2152623
Downloads
Published
Issue
Section
License
Copyright (c) 2025 Advances in Biotechnology & Genetic Engineering

This work is licensed under a Creative Commons Attribution 4.0 International License.