A Plasmid-Encoded FetMP-Fls Iron Uptake System Confers Selective Advantages to <i>Salmonella enterica</i> Serovar Typhimurium in Growth under Iron-Restricted Conditions and for Infection of Mammalian Host Cells
The resistance plasmid pUO-StVR2, derived from virulence plasmid pSLT, is widespread in clinical isolates of <i>Salmonella enterica</i> serovar Typhimurium recovered in Spain and other European countries. pUO-StVR2 carries several genes encoding a FetMP-Fls system, which could be involve...
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MDPI AG
2020-04-01
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| Series: | Microorganisms |
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| Online Access: | https://www.mdpi.com/2076-2607/8/5/630 |
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| author | Vanesa García Ana Herrero-Fresno Rosaura Rodicio Alfonso Felipe-López Ignacio Montero John E. Olsen Michael Hensel María Rosario Rodicio |
| author_facet | Vanesa García Ana Herrero-Fresno Rosaura Rodicio Alfonso Felipe-López Ignacio Montero John E. Olsen Michael Hensel María Rosario Rodicio |
| author_sort | Vanesa García |
| collection | DOAJ |
| description | The resistance plasmid pUO-StVR2, derived from virulence plasmid pSLT, is widespread in clinical isolates of <i>Salmonella enterica</i> serovar Typhimurium recovered in Spain and other European countries. pUO-StVR2 carries several genes encoding a FetMP-Fls system, which could be involved in iron uptake. We therefore analyzed <i>S</i>. Typhimurium LSP 146/02, a clinical strain selected as representative of the isolates carrying the plasmid, and an otherwise isogenic mutant lacking four genes (<i>fetMP</i>-<i>flsDA</i>) of the <i>fetMP</i>-<i>fls</i> region. Growth curves and determination of the intracellular iron content under iron-restricted conditions demonstrated that deletion of these genes impairs iron acquisition. Thus, under these conditions, the mutant grew significantly worse than the wild-type strain, its iron content was significantly lower, and it was outcompeted by the wild-type strain in competition assays. Importantly, the strain lacking the <i>fetMP</i>-<i>flsDA</i> genes was less invasive in cultured epithelial HeLa cells and replicated poorly upon infection of RAW264.7 macrophages. The genes were introduced into <i>S</i>. Typhimurium ATCC 14028, which lacks the FetMP-Fls system, and this resulted in increased growth under iron limitation as well as an increased ability to multiply inside macrophages. These findings indicate that the FetMP-Fls iron acquisition system exceeds the benefits conferred by the other high-affinity iron uptake systems carried by ATCC 14028 and LSP 146/02. We proposed that effective iron acquisition by this system in conjunction with antimicrobial resistance encoded from the same plasmid have greatly contributed to the epidemic success of <i>S</i>. Typhimurium isolates harboring pUO-StVR2. |
| first_indexed | 2024-03-10T20:11:31Z |
| format | Article |
| id | doaj.art-7aa33487df4f4972a671055dddd898a3 |
| institution | Directory Open Access Journal |
| issn | 2076-2607 |
| language | English |
| last_indexed | 2024-03-10T20:11:31Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Microorganisms |
| spelling | doaj.art-7aa33487df4f4972a671055dddd898a32023-11-19T22:52:01ZengMDPI AGMicroorganisms2076-26072020-04-018563010.3390/microorganisms8050630A Plasmid-Encoded FetMP-Fls Iron Uptake System Confers Selective Advantages to <i>Salmonella enterica</i> Serovar Typhimurium in Growth under Iron-Restricted Conditions and for Infection of Mammalian Host CellsVanesa García0Ana Herrero-Fresno1Rosaura Rodicio2Alfonso Felipe-López3Ignacio Montero4John E. Olsen5Michael Hensel6María Rosario Rodicio7Department of Functional Biology, Section of Microbiology, University of Oviedo, 33006 Oviedo, SpainDepartment of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 1870 Frederiksberg, DenmarkDepartment of Biochemistry and Molecular Biology, University of Oviedo, 33006 Oviedo, SpainDivision of Microbiology, University of Osnabrück, 49076 Osnabrück, GermanyDepartment of Functional Biology, Section of Microbiology, University of Oviedo, 33006 Oviedo, SpainDepartment of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 1870 Frederiksberg, DenmarkDivision of Microbiology, University of Osnabrück, 49076 Osnabrück, GermanyDepartment of Functional Biology, Section of Microbiology, University of Oviedo, 33006 Oviedo, SpainThe resistance plasmid pUO-StVR2, derived from virulence plasmid pSLT, is widespread in clinical isolates of <i>Salmonella enterica</i> serovar Typhimurium recovered in Spain and other European countries. pUO-StVR2 carries several genes encoding a FetMP-Fls system, which could be involved in iron uptake. We therefore analyzed <i>S</i>. Typhimurium LSP 146/02, a clinical strain selected as representative of the isolates carrying the plasmid, and an otherwise isogenic mutant lacking four genes (<i>fetMP</i>-<i>flsDA</i>) of the <i>fetMP</i>-<i>fls</i> region. Growth curves and determination of the intracellular iron content under iron-restricted conditions demonstrated that deletion of these genes impairs iron acquisition. Thus, under these conditions, the mutant grew significantly worse than the wild-type strain, its iron content was significantly lower, and it was outcompeted by the wild-type strain in competition assays. Importantly, the strain lacking the <i>fetMP</i>-<i>flsDA</i> genes was less invasive in cultured epithelial HeLa cells and replicated poorly upon infection of RAW264.7 macrophages. The genes were introduced into <i>S</i>. Typhimurium ATCC 14028, which lacks the FetMP-Fls system, and this resulted in increased growth under iron limitation as well as an increased ability to multiply inside macrophages. These findings indicate that the FetMP-Fls iron acquisition system exceeds the benefits conferred by the other high-affinity iron uptake systems carried by ATCC 14028 and LSP 146/02. We proposed that effective iron acquisition by this system in conjunction with antimicrobial resistance encoded from the same plasmid have greatly contributed to the epidemic success of <i>S</i>. Typhimurium isolates harboring pUO-StVR2.https://www.mdpi.com/2076-2607/8/5/630<i>Salmonella enterica</i> serovar Typhimuriumhigh-affinity iron uptake systemsFetMP-Fls systemiron-restrictive conditionsepithelial cells invasionmacrophage intracellular replication |
| spellingShingle | Vanesa García Ana Herrero-Fresno Rosaura Rodicio Alfonso Felipe-López Ignacio Montero John E. Olsen Michael Hensel María Rosario Rodicio A Plasmid-Encoded FetMP-Fls Iron Uptake System Confers Selective Advantages to <i>Salmonella enterica</i> Serovar Typhimurium in Growth under Iron-Restricted Conditions and for Infection of Mammalian Host Cells Microorganisms <i>Salmonella enterica</i> serovar Typhimurium high-affinity iron uptake systems FetMP-Fls system iron-restrictive conditions epithelial cells invasion macrophage intracellular replication |
| title | A Plasmid-Encoded FetMP-Fls Iron Uptake System Confers Selective Advantages to <i>Salmonella enterica</i> Serovar Typhimurium in Growth under Iron-Restricted Conditions and for Infection of Mammalian Host Cells |
| title_full | A Plasmid-Encoded FetMP-Fls Iron Uptake System Confers Selective Advantages to <i>Salmonella enterica</i> Serovar Typhimurium in Growth under Iron-Restricted Conditions and for Infection of Mammalian Host Cells |
| title_fullStr | A Plasmid-Encoded FetMP-Fls Iron Uptake System Confers Selective Advantages to <i>Salmonella enterica</i> Serovar Typhimurium in Growth under Iron-Restricted Conditions and for Infection of Mammalian Host Cells |
| title_full_unstemmed | A Plasmid-Encoded FetMP-Fls Iron Uptake System Confers Selective Advantages to <i>Salmonella enterica</i> Serovar Typhimurium in Growth under Iron-Restricted Conditions and for Infection of Mammalian Host Cells |
| title_short | A Plasmid-Encoded FetMP-Fls Iron Uptake System Confers Selective Advantages to <i>Salmonella enterica</i> Serovar Typhimurium in Growth under Iron-Restricted Conditions and for Infection of Mammalian Host Cells |
| title_sort | plasmid encoded fetmp fls iron uptake system confers selective advantages to i salmonella enterica i serovar typhimurium in growth under iron restricted conditions and for infection of mammalian host cells |
| topic | <i>Salmonella enterica</i> serovar Typhimurium high-affinity iron uptake systems FetMP-Fls system iron-restrictive conditions epithelial cells invasion macrophage intracellular replication |
| url | https://www.mdpi.com/2076-2607/8/5/630 |
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