PmtA Regulates Pyocyanin Expression and Biofilm Formation in Pseudomonas aeruginosa

The opportunistic pathogen Pseudomonas aeruginosa expresses a small molecular weight, cysteine-rich protein (PmtA), identified as a metallothionein (MT) protein family member. The MT family proteins have been well-characterized in eukaryotes as essential for zinc and copper homeostasis, protection a...

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Autores principales:	Amy V. Thees, Kathryn M. Pietrosimone, Clare K. Melchiorre, Jeremiah N. Marden, Joerg Graf, Michael A. Lynes, Michele Maltz-Matyschsyk
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	metallothionein pyocyanin biofilm antibiotic resistance virulence Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/77c892228e774e999d2a0b37fafb3267
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spelling	oai:doaj.org-article:77c892228e774e999d2a0b37fafb32672021-11-15T06:30:21ZPmtA Regulates Pyocyanin Expression and Biofilm Formation in Pseudomonas aeruginosa1664-302X10.3389/fmicb.2021.789765https://doaj.org/article/77c892228e774e999d2a0b37fafb32672021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmicb.2021.789765/fullhttps://doaj.org/toc/1664-302XThe opportunistic pathogen Pseudomonas aeruginosa expresses a small molecular weight, cysteine-rich protein (PmtA), identified as a metallothionein (MT) protein family member. The MT family proteins have been well-characterized in eukaryotes as essential for zinc and copper homeostasis, protection against oxidative stress, and the ability to modify a variety of immune activities. Bacterial MTs share sequence homology, antioxidant chemistry, and heavy metal-binding capacity with eukaryotic MTs, however, the impact of bacterial MTs on virulence and infection have not been well-studied. In the present study, we investigated the role of PmtA in P. aeruginosa PAO1 using a PmtA-deficient strain (ΔpmtA). Here we demonstrated the virulence factor, pyocyanin, relies on the expression of PmtA. We showed that PmtA may be protective against oxidative stress, as an alternative antioxidant, glutathione, can rescue pyocyanin expression. Furthermore, the expression of phzM, which encodes a pyocyanin precursor enzyme, was decreased in the ΔpmtA mutant during early stationary phase. Upregulated pmtA expression was previously detected in confluent biofilms, which are essential for chronic infection, and we observed that the ΔpmtA mutant was disrupted for biofilm formation. As biofilms also modulate antibiotic susceptibility, we examined the ΔpmtA mutant susceptibility to antibiotics and found that the ΔpmtA mutant is more susceptible to cefepime and ciprofloxacin than the wild-type strain. Finally, we observed that the deletion of pmtA results in decreased virulence in a waxworm model. Taken together, our results support the conclusion that PmtA is necessary for the full virulence of P. aeruginosa and may represent a potential target for therapeutic intervention.Amy V. TheesKathryn M. PietrosimoneClare K. MelchiorreJeremiah N. MardenJoerg GrafMichael A. LynesMichele Maltz-MatyschsykFrontiers Media S.A.articlemetallothioneinpyocyaninbiofilmantibiotic resistancevirulenceMicrobiologyQR1-502ENFrontiers in Microbiology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	metallothionein pyocyanin biofilm antibiotic resistance virulence Microbiology QR1-502
spellingShingle	metallothionein pyocyanin biofilm antibiotic resistance virulence Microbiology QR1-502 Amy V. Thees Kathryn M. Pietrosimone Clare K. Melchiorre Jeremiah N. Marden Joerg Graf Michael A. Lynes Michele Maltz-Matyschsyk PmtA Regulates Pyocyanin Expression and Biofilm Formation in Pseudomonas aeruginosa
description	The opportunistic pathogen Pseudomonas aeruginosa expresses a small molecular weight, cysteine-rich protein (PmtA), identified as a metallothionein (MT) protein family member. The MT family proteins have been well-characterized in eukaryotes as essential for zinc and copper homeostasis, protection against oxidative stress, and the ability to modify a variety of immune activities. Bacterial MTs share sequence homology, antioxidant chemistry, and heavy metal-binding capacity with eukaryotic MTs, however, the impact of bacterial MTs on virulence and infection have not been well-studied. In the present study, we investigated the role of PmtA in P. aeruginosa PAO1 using a PmtA-deficient strain (ΔpmtA). Here we demonstrated the virulence factor, pyocyanin, relies on the expression of PmtA. We showed that PmtA may be protective against oxidative stress, as an alternative antioxidant, glutathione, can rescue pyocyanin expression. Furthermore, the expression of phzM, which encodes a pyocyanin precursor enzyme, was decreased in the ΔpmtA mutant during early stationary phase. Upregulated pmtA expression was previously detected in confluent biofilms, which are essential for chronic infection, and we observed that the ΔpmtA mutant was disrupted for biofilm formation. As biofilms also modulate antibiotic susceptibility, we examined the ΔpmtA mutant susceptibility to antibiotics and found that the ΔpmtA mutant is more susceptible to cefepime and ciprofloxacin than the wild-type strain. Finally, we observed that the deletion of pmtA results in decreased virulence in a waxworm model. Taken together, our results support the conclusion that PmtA is necessary for the full virulence of P. aeruginosa and may represent a potential target for therapeutic intervention.
format	article
author	Amy V. Thees Kathryn M. Pietrosimone Clare K. Melchiorre Jeremiah N. Marden Joerg Graf Michael A. Lynes Michele Maltz-Matyschsyk
author_facet	Amy V. Thees Kathryn M. Pietrosimone Clare K. Melchiorre Jeremiah N. Marden Joerg Graf Michael A. Lynes Michele Maltz-Matyschsyk
author_sort	Amy V. Thees
title	PmtA Regulates Pyocyanin Expression and Biofilm Formation in Pseudomonas aeruginosa
title_short	PmtA Regulates Pyocyanin Expression and Biofilm Formation in Pseudomonas aeruginosa
title_full	PmtA Regulates Pyocyanin Expression and Biofilm Formation in Pseudomonas aeruginosa
title_fullStr	PmtA Regulates Pyocyanin Expression and Biofilm Formation in Pseudomonas aeruginosa
title_full_unstemmed	PmtA Regulates Pyocyanin Expression and Biofilm Formation in Pseudomonas aeruginosa
title_sort	pmta regulates pyocyanin expression and biofilm formation in pseudomonas aeruginosa
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/77c892228e774e999d2a0b37fafb3267
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PmtA Regulates Pyocyanin Expression and Biofilm Formation in Pseudomonas aeruginosa

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