Sains Malaysiana 55(9)(2026): 1454-1461
http://doi.org/10.17576/jsm-2026-5509-04
Growth Inhibition Underlies the Suppression of QseBC-Regulated Virulence by Trace Amines and Dopamine
(Perencatan Pertumbuhan Mendasari Penindasan Virulens yang Dikawal QseBC oleh Surih Amina dan Dopamin)
ARIF LUQMAN1, RUBEN AMIAN RUIZ2, FRIEDRICH GÖTZ2 & MAYA SHOVITRI1,*
1Department of Biology, Institut Teknologi Sepuluh Nopember, 60111 Surabaya, Indonesia
2Microbial Genetics, University of Tübingen, Geschwister-Scholl-Platz, Auf der Morgenstelle, 72076 Tübingen, Germany
Received: 8
December 2025/Accepted: 18 August 2026
*Corresponding
author; email: mshovitri@its.ac.id
Abstract
Trace amines (TAs) and dopamine are neuroactive compounds
that can interact with bacterial adrenergic receptors like QseC,
a membrane-bound sensor histidine kinase. QseC is the
core sensing component of the QseBC two-component
system, which regulates virulence gene expression in Gram-negative pathogens
via quorum sensing. This study investigated whether TAs (tryptamine,
phenethylamine, tyramine) and dopamine act as specific QseBC modulators or exert indirect effects via growth inhibition in Escherichia
coli O157:H7, Salmonella typhimurium, and Vibrio cholerae
O1. Our results show that at high concentrations (≥ 50-250 µg/mL), these
compounds significantly inhibited bacterial motility and modestly
downregulated QseBC-regulated virulence genes (eae, ler, sipA, sopB) and Shiga
toxin production. However, these effects were concurrent with a pronounced,
concentration-dependent growth inhibition. While dopamine exhibited
iron-chelating activity in the CAS assay, this did not mitigate its
growth-suppressive effect. In conclusion, the anti-virulence effects of TAs and
dopamine are secondary consequences of a general antibacterial activity that
compromises cellular fitness, rather than a result of specific QseBC antagonism.
Keywords: Bacterial virulence; dopamine; growth
inhibition; QseBC; trace amines
Abstrak
Surih amina (TA) dan dopamin adalah sebatian neuroaktif yang boleh berinteraksi dengan reseptor adrenergik bakteria seperti QseC, yang merupakan histidin kinase sensor yang terikat membran. QseC adalah komponen pengesanan teras sistem dua komponen QseBC yang mengawal selia pengekspresan gen virulens dalam patogen Gram-negatif melalui pengesanan kuorum. Penyelidikan ini mengkaji sama ada TA (triptamina, fenetilamina, tiramina) dan dopamin bertindak sebagai modulator QseBC khusus atau memberikan kesan tidak langsung melalui perencatan pertumbuhan dalam Escherichia coli O157:H7, Salmonella
typhimurium, dan Vibrio cholerae
O1. Hasil menunjukkan bahawa pada kepekatan tinggi (≥ 50-250
µg/mL), sebatian ini menghalang motiliti bakteria dengan ketara serta menurunkan pengekspresan gen virulens yang dikawal selia oleh QseBC (eae, ler, sipA, sopB) dan penghasilan toksin Shiga. Walau bagaimanapun, kesan ini serentak dengan perencatan pertumbuhan yang ketara dan bergantung kepada kepekatan. Walaupun dopamin menunjukkan aktiviti pengkelat zat besi dalam ujian CAS, ini tidak mengurangkan kesan penindasan pertumbuhannya. Kesimpulannya, kesan anti-virulens TA dan dopamin adalah akibat sekunder daripada aktiviti antibakteria umum yang menjejaskan kecergasan sel dan bukannya hasil daripada antagonisme QseBC tertentu.
Kata kunci: Dopamin; kevirulenan bakteria; perencatan pertumbuhan; QseBC; surih amina
REFERENCES
Bearson, B.L., Bearson, S.M.,
Lee, I.S. & Brunelle, B.W. 2010. The Salmonella enterica serovar
Typhimurium QseB response regulator negatively
regulates bacterial motility and swine colonization in the absence of the QseC sensor kinase. Microbial Pathogenesis 48(6):
214-219. https://doi.org/10.1016/j.micpath.2010.03.005
Clarke, M.B., Hughes, D.T., Zhu, C., Boedeker, E.C. & Sperandio,
V. 2006. The QseC sensor kinase: A bacterial
adrenergic receptor. PNAS 103(27): 10420-10425. https://doi.org/10.1073/pnas.0604343103
Croze, O.A., Ferguson, G.P., Cates, M.E. & Poon,
W.C. 2011. Migration of chemotactic bacteria in soft agar: Role of gel
concentration. Biophysic Journal 101(3):
525-534. https://doi.org/10.1016/j.bpj.2011.06.023
Dichtl, S., Demetz, E., Haschka, D., Tymoszuk, P., Petzer, V., Nairz, M., Seifert,
M., Hoffmann, A., Brigo, N., Wurzner,
R., Theurl, I., Karlinsey,
J.E., Fang, F.C. & Weiss, G. 2019. Dopamine is a siderophore-like iron
chelator that promotes Salmonella enterica Serovar Typhimurium virulence
in mice. mBio 10(1): e02624-18. https://doi.org/10.1128/mBio.02624-18
Ebner, P., Luqman, A.,
Reichert, S., Hauf, K., Popella,
P., Forchhammer, K., Otto, M. & Gotz, F. 2017. Non-classical protein excretion is boosted
by PSMalpha-induced cell leakage. Cell Reports 20(6):
1278-1286. https://doi.org/10.1016/j.celrep.2017.07.045
Ebner, P., Prax, M., Nega, M., Koch, I., Dube, L., Yu, W., Rinker, J., Popella, P., Flotenmeyer, M.
& Gotz, F. 2015. Excretion of cytoplasmic
proteins (ECP) in Staphylococcus aureus. Molecular Microbiology 97(4):
775-789. https://doi.org/10.1111/mmi.13065
Febrianti, A., Prasetyo, E.N., Zulaika, E. & Luqman, A.
2025. The effects of dopamine at physiological concentration on the growth and
biofilm formation of Staphylococcus aureus, Staphylococcus
epidermidis, and Escherichia coli. Biologica Nyssana16(1): 21F.
Halang, P., Toulouse, C., Geissel,
B., Michel, B., Flauger, B., Muller, M., Voegele, R.T., Stefanski, V.
& Steuber, J. 2015. Response of Vibrio
cholerae to the catecholamine hormones epinephrine and norepinephrine. Journal
of Bacteriology 197(24): 3769-3778. https://doi.org/10.1128/JB.00345-15
Hughes, D.T., Clarke, M.B., Yamamoto, K., Rasko, D.A. & Sperandio, V.
2009. The QseC adrenergic signaling cascade in enterohemorrhagic E. coli (EHEC). PLoS Pathogens 5(8): e1000553. https://doi.org/10.1371/journal.ppat.1000553
Kim, C.S., Gatsios,
A., Cuesta, S., Lam, Y.C., Wei, Z., Chen, H., Russell, R.M., Shine, E.E., Wang,
R., Wyche, T.P., Piizzi, G., Flavell, R.A., Palm,
N.W., Sperandio, V. & Crawford, J.M. 2020.
Characterization of autoinducer-3 structure and biosynthesis in E. coli. ACS Central Science 6(2): 197-206. https://doi.org/10.1021/acscentsci.9b01076
Luqman, A. 2023. The orchestra of human bacteriome by
hormones. Microbial Pathogenesis 180: 106125. https://doi.org/10.1016/j.micpath.2023.106125
Luqman, A. & Ohlsen, K.
2024. Adrenergic system: A gateway of reciprocal signaling between host and bacteria. Current Opinion in Endocrine and Metabolic
Research 35: 100523. https://doi.org/https://doi.org/10.1016/j.coemr.2024.100523
Luqman, A., Kharisma, V.D.,
Ruiz, R.A. & Gotz, F. 2020a. In silico and in vitro study of trace amines (TA) and dopamine (DOP) interaction with
human Alpha 1-Adrenergic receptor and the bacterial adrenergic receptor QseC. Cellular Physiology & Biochemistry 54(5):
888-898. https://doi.org/10.33594/000000276
Luqman, A., Zabel, S., Rahmdel,
S., Merz, B., Gruenheit, N., Harter, J., Nieselt, K. & Gotz, F. 2020b.
The neuromodulator-encoding sadA gene is
widely distributed in the human skin microbiome. Frontiers in Microbiology 11:
573679. https://doi.org/10.3389/fmicb.2020.573679
Luqman, A., Ruiz, R.A., Götz,
F., Shovitri, M., Zulaika,
E., Hidayati, D. & Saputro,
T.B. 2021. The effect of tryptamine on Serratia marcescens, Pseudomonas
aeruginosa and Escherichia coli. Malaysian Journal of
Microbiology 17(3): 333.
Lyte, M. 2013. Microbial endocrinology in the
microbiome-gut-brain axis: How bacterial production and utilization of
neurochemicals influence behavior. PLoS Pathogens 9(11): e1003726. https://doi.org/10.1371/journal.ppat.1003726
Moreira, C.G. & Sperandio,
V. 2012. Interplay between the QseC and QseE bacterial adrenergic sensor kinases in Salmonella
enterica serovar Typhimurium pathogenesis. Infect Immun. 80(12):
4344-4353. https://doi.org/10.1128/IAI.00803-12
Moreira, C.G., Weinshenker,
D. & Sperandio, V. 2010. QseC mediates Salmonella enterica serovar Typhimurium virulence in vitro and in vivo. Infection & Immunity 78(3): 914-926. https://doi.org/10.1128/IAI.01038-09
Munter, S., Way, M. & Frischknecht,
F. 2006. Signaling during pathogen infection. Science
STKE 2006(335): re5. https://doi.org/10.1126/stke.3352006re5
Murakami, C., Tanaka, A.R., Sato, Y., Kimura, Y.
& Morimoto, K. 2021. Easy detection of siderophore production in diluted
growth media using an improved CAS reagent. Journal of Microbiological Methods 189: 106310. https://doi.org/10.1016/j.mimet.2021.106310
Nair, V.G., Srinandan,
C.S., Rajesh, Y., Narbhavi, D., Anupriya,
A., Prabhusaran, N. & Nagarajan, S. 2024.
Biogenic amine tryptamine in human vaginal probiotic isolates mediates matrix
inhibition and thwarts uropathogenic E. coli biofilm. Scientific Reports 14(1): 15387. https://doi.org/10.1038/s41598-024-65780-0
Olive, A.J. & Sassetti,
C.M. 2016. Metabolic crosstalk between host and pathogen: Sensing, adapting and
competing. Nature Reviews Microbiology 14(4): 221-234. https://doi.org/10.1038/nrmicro.2016.12
Otaru, N., Greppi, A., Plüss, S., Zünd, J., Mujezinovic, D., Baur, J., Koleva,
E., Lacroix, C. & Pugin, B. 2024. Intestinal bacteria-derived tryptamine
and its impact on human gut microbiota. Frontiers in Microbiomes 3:
1373335.
Perraud, Q., Kuhn, L., Fritsch, S., Graulier,
G., Gasser, V., Normant, V., Hammann,
P. & Schalk, I.J. 2022. Opportunistic use of catecholamine
neurotransmitters as siderophores to access iron by Pseudomonas aeruginosa. Environmental Microbioogy24(2): 878-893. https://doi.org/10.1111/1462-2920.15372
Rahmdel, S., Luqman, A. & Gotz, F. 2025. Microbiota-derived aromatic amino acid
decarboxylases: Linking microbial fitness and host neurochemical communication. mBio 16: e02052-25. https://doi.org/10.1128/mbio.02052-25
Schwyn, B. & Neilands,
J.B. 1987. Universal chemical assay for the detection and determination of
siderophores. Analytical Biochemistry 160(1): 47-56. https://doi.org/10.1016/0003-2697(87)90612-9
Sperandio, V., Torres, A.G. & Kaper,
J.B. 2002. Quorum sensing Escherichia coli regulators B and C (QseBC): A novel two-component regulatory system involved in
the regulation of flagella and motility by quorum sensing in E. coli. Molecular
Microbiology 43(3): 809-821. https://doi.org/10.1046/j.1365-2958.2002.02803.x
Yang, D., Kong, Y., Sun, W., Kong, W. & Shi,
Y. 2019. A dopamine-responsive signal transduction controls transcription of Salmonella
enterica serovar Typhimurium virulence genes. mBio 10(2):
10.1128/mbio.02772-18. https://doi.org/10.1128/mBio.02772-18
Yang, Q., Anh, N.D., Bossier, P. & Defoirdt, T. 2014. Norepinephrine and dopamine increase
motility, biofilm formation, and virulence of Vibrio harveyi. Frontiers in Microbiology 5: 584. https://doi.org/10.3389/fmicb.2014.00584