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Inactivation of the quorum-sensing transcriptional regulators LasR or RhlR does not suppress the expression of virulence factors and the virulence of Pseudomonas aeruginosa PAO1.
Microbiology (Reading). 2019 04; 165(4):425-432.M

Abstract

Pseudomonas aeruginosa is an environmental bacterium but is also an opportunistic pathogen. The aim of this work is to evaluate the contribution of P. aeruginosa LasR and RhlR transcriptional regulators of the quorum-sensing response (QSR) to the production of virulence factors, and to its virulence in a mouse abscess model. The QSR is a complex regulatory network that modulates the expression of several virulence factors, including elastase, pyocyanin and rhamnolipids. LasR, when complexed with the auto-inducer 3-oxo-dodecanoyl lactone (3O-C12-HSL), produced by LasI, is at the top of the QSR regulatory cascade since it activates transcription of some genes encoding virulence factors (such as the gene coding for elastase, lasB) and also transcription of both rhlR and rhlI, encoding the synthase of the auto-inducer butanoyl-homoserine lactone (C4-HSL). In turn RhlR, coupled with C4-HSL, activates the transcription of genes encoding for the enzymes involved in pyocyanin and rhamnolipid production. Several efforts have been made to obtain inhibitors of LasR activity that would suppress the QSR. However, these attempts have used chemical compounds that might not be specific for LasR inactivation. In this work we show that individual inactivation of either lasR or rhlR did not block the QSR, nor did it impair P. aeruginosa virulence, and that even a lasR rhlR double mutant still presented residual virulence, even lacking the production of virulence factors. These results show that the inhibition of either lasR or rhlR is not a straightforward approach to blocking P. aeruginosa virulence, due to the great complexity of the QSR.

Authors+Show Affiliations

1​Departamento de Biología Molecular y Biotecnología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México Apdo, Postal 70228, Ciudad Universitaria, 04510, CDMX, México.2​Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México, CDMX, México.3​Departamento de Microbiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca Mor, México.4​Colegio de Postgraduados, Campus Montecillo, Texcoco, México.4​Colegio de Postgraduados, Campus Montecillo, Texcoco, México.5​Departamento de Genética Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Ciudad Universitaria, 04510, CDMX, México.5​Departamento de Genética Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Ciudad Universitaria, 04510, CDMX, México.1​Departamento de Biología Molecular y Biotecnología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México Apdo, Postal 70228, Ciudad Universitaria, 04510, CDMX, México.1​Departamento de Biología Molecular y Biotecnología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México Apdo, Postal 70228, Ciudad Universitaria, 04510, CDMX, México.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30707095

Citation

Soto-Aceves, Martín P., et al. "Inactivation of the Quorum-sensing Transcriptional Regulators LasR or RhlR Does Not Suppress the Expression of Virulence Factors and the Virulence of Pseudomonas Aeruginosa PAO1." Microbiology (Reading, England), vol. 165, no. 4, 2019, pp. 425-432.
Soto-Aceves MP, Cocotl-Yañez M, Merino E, et al. Inactivation of the quorum-sensing transcriptional regulators LasR or RhlR does not suppress the expression of virulence factors and the virulence of Pseudomonas aeruginosa PAO1. Microbiology (Reading). 2019;165(4):425-432.
Soto-Aceves, M. P., Cocotl-Yañez, M., Merino, E., Castillo-Juárez, I., Cortés-López, H., González-Pedrajo, B., Díaz-Guerrero, M., Servín-González, L., & Soberón-Chávez, G. (2019). Inactivation of the quorum-sensing transcriptional regulators LasR or RhlR does not suppress the expression of virulence factors and the virulence of Pseudomonas aeruginosa PAO1. Microbiology (Reading, England), 165(4), 425-432. https://doi.org/10.1099/mic.0.000778
Soto-Aceves MP, et al. Inactivation of the Quorum-sensing Transcriptional Regulators LasR or RhlR Does Not Suppress the Expression of Virulence Factors and the Virulence of Pseudomonas Aeruginosa PAO1. Microbiology (Reading). 2019;165(4):425-432. PubMed PMID: 30707095.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inactivation of the quorum-sensing transcriptional regulators LasR or RhlR does not suppress the expression of virulence factors and the virulence of Pseudomonas aeruginosa PAO1. AU - Soto-Aceves,Martín P, AU - Cocotl-Yañez,Miguel, AU - Merino,Enrique, AU - Castillo-Juárez,Israel, AU - Cortés-López,Humberto, AU - González-Pedrajo,Bertha, AU - Díaz-Guerrero,Miguel, AU - Servín-González,Luis, AU - Soberón-Chávez,Gloria, Y1 - 2019/02/01/ PY - 2019/2/2/pubmed PY - 2020/2/6/medline PY - 2019/2/2/entrez KW - Pseudomonas aeruginosa KW - quorum-sensing response KW - virulence SP - 425 EP - 432 JF - Microbiology (Reading, England) JO - Microbiology (Reading) VL - 165 IS - 4 N2 - Pseudomonas aeruginosa is an environmental bacterium but is also an opportunistic pathogen. The aim of this work is to evaluate the contribution of P. aeruginosa LasR and RhlR transcriptional regulators of the quorum-sensing response (QSR) to the production of virulence factors, and to its virulence in a mouse abscess model. The QSR is a complex regulatory network that modulates the expression of several virulence factors, including elastase, pyocyanin and rhamnolipids. LasR, when complexed with the auto-inducer 3-oxo-dodecanoyl lactone (3O-C12-HSL), produced by LasI, is at the top of the QSR regulatory cascade since it activates transcription of some genes encoding virulence factors (such as the gene coding for elastase, lasB) and also transcription of both rhlR and rhlI, encoding the synthase of the auto-inducer butanoyl-homoserine lactone (C4-HSL). In turn RhlR, coupled with C4-HSL, activates the transcription of genes encoding for the enzymes involved in pyocyanin and rhamnolipid production. Several efforts have been made to obtain inhibitors of LasR activity that would suppress the QSR. However, these attempts have used chemical compounds that might not be specific for LasR inactivation. In this work we show that individual inactivation of either lasR or rhlR did not block the QSR, nor did it impair P. aeruginosa virulence, and that even a lasR rhlR double mutant still presented residual virulence, even lacking the production of virulence factors. These results show that the inhibition of either lasR or rhlR is not a straightforward approach to blocking P. aeruginosa virulence, due to the great complexity of the QSR. SN - 1465-2080 UR - https://www.unboundmedicine.com/medline/citation/30707095/Inactivation_of_the_quorum_sensing_transcriptional_regulators_LasR_or_RhlR_does_not_suppress_the_expression_of_virulence_factors_and_the_virulence_of_Pseudomonas_aeruginosa_PAO1_ L2 - http://mic.microbiologyresearch.org/pubmed/content/journal/micro/10.1099/mic.0.000778 DB - PRIME DP - Unbound Medicine ER -