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Virulence Conferred by PumA Toxin from the Plasmid-Encoded PumAB Toxin-Antitoxin System is Regulated by Quorum System

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Abstract

Toxin-antitoxin (TA) systems are small genetic elements composed of a toxin gene and its cognate antitoxin that are important for plasmid stabilization (plasmid-encoded) and bacterial virulence (chromosome-encoded). These systems are also related to biofilm and persister cell formations. Pseudomonas aeruginosa is an antibiotic-resistant human pathogen that produces virulence factors modulated by quorum sensing (QS) and can form biofilms. The type II PumAB TA system of pUM505, isolated from a clinical strain of P. aeruginosa, confers plasmid stability. Additionally, the PumA toxin increases P. aeruginosa virulence and is neutralized by the PumB antitoxin. In this study, we determined whether virulence conferred by PumA toxin is regulated by QS. The pumA gene was transferred to P. aeruginosa lasI/rhlI, a mutant strain in the LasI and RhlI QS systems, to analyze the effect on virulence of the transformants. pumA transfer did not increase bacterial virulence in lettuce and Caenorhabditis elegans, suggesting that the virulence conferred by PumA requires QS modulation. pumA mRNA levels drastically decreased in the P. aeruginosa lasI/rhlI (pUC_pumA) strain, suggesting positive regulation of pumA gene expression by QS. Supplementation of the growth medium of P. aeruginosa lasI/rhlI (pUC_pumA) with C4-AHL and 3-oxo-C12-AHL autoinducers increased pumA mRNA levels and restored bacterial virulence, suggesting that both autoinducers complemented the mutations and positively regulated the toxic effects of PumA. This strengthened the hypothesis that QS regulates bacterial virulence conferred by the PumA toxin. Thus, this report establishes an important function of QS in the virulence conferred by plasmid-encoded TA systems in bacterial pathogens.

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Acknowledgements

This work was supported by grants from Coordinación de la Investigación Científica (UMSNH; 2.6 and 2.35). KCH-R and MIV-M were supported by postgraduate fellowships from CONACYT.

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Authors and Affiliations

  1. Instituto de Investigaciones Químico-Biológicas, Universidad Michoacana de San Nicolás de Hidalgo, Edificio B-3, Ciudad Universitaria, 58030, Morelia, Michoacán, Mexico

    Karen C. Hernández-Ramírez, Marco I. Valle-Maldonado, León F. Ruíz-Herrera, Victor Meza-Carmen & Martha I. Ramírez-Díaz

  2. Facultad de Químico Farmacobiología, Universidad Michoacana de San Nicolás de Hidalgo, Morelia, Michoacán, Mexico

    Brenda Valerio-Arellano

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  1. Karen C. Hernández-Ramírez
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  2. Brenda Valerio-Arellano
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  3. Marco I. Valle-Maldonado
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  4. León F. Ruíz-Herrera
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  5. Victor Meza-Carmen
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  6. Martha I. Ramírez-Díaz
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Contributions

KC H-R, B V-A and MI V-M, data acquisition, analysis, and data interpretation, LF R-H and V M-C, reagents, analysis; V M-C data interpretation, and critical revision of the article for intellectual content; MI R-D, conception and design of the work, data analysis and interpretation, and drafting of the article.

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Correspondence to Martha I. Ramírez-Díaz.

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Hernández-Ramírez, K.C., Valerio-Arellano, B., Valle-Maldonado, M.I. et al. Virulence Conferred by PumA Toxin from the Plasmid-Encoded PumAB Toxin-Antitoxin System is Regulated by Quorum System. Curr Microbiol 77, 2535–2543 (2020). https://doi.org/10.1007/s00284-020-02083-3

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