A plasmid-encoded fetmp-fls iron uptake system confers selective advantages to salmonella enterica serovar typhimurium in growth under iron-restricted conditions and for infection of mammalian host cells
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A plasmid-encoded fetmp-fls iron uptake system confers selective advantages to salmonella enterica serovar typhimurium in growth under iron-restricted conditions and for infection of mammalian host cells. / García, Vanesa; Herrero-Fresno, Ana; Rodicio, Rosaura; Felipe-López, Alfonso; Montero, Ignacio; Olsen, John E.; Hensel, Michael; Rodicio, María Rosario.
I: Microorganisms, Bind 8, Nr. 5, 630, 2020.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - A plasmid-encoded fetmp-fls iron uptake system confers selective advantages to salmonella enterica serovar typhimurium in growth under iron-restricted conditions and for infection of mammalian host cells
AU - García, Vanesa
AU - Herrero-Fresno, Ana
AU - Rodicio, Rosaura
AU - Felipe-López, Alfonso
AU - Montero, Ignacio
AU - Olsen, John E.
AU - Hensel, Michael
AU - Rodicio, María Rosario
PY - 2020
Y1 - 2020
N2 - The resistance plasmid pUO-StVR2, derived from virulence plasmid pSLT, is widespread in clinical isolates of Salmonella enterica 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 S. Typhimurium LSP 146/02, a clinical strain selected as representative of the isolates carrying the plasmid, and an otherwise isogenic mutant lacking four genes (fetMP-flsDA) of the fetMP-fls 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 fetMP-flsDA genes was less invasive in cultured epithelial HeLa cells and replicated poorly upon infection of RAW264.7 macrophages. The genes were introduced into S. 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 S. Typhimurium isolates harboring pUO-StVR2.
AB - The resistance plasmid pUO-StVR2, derived from virulence plasmid pSLT, is widespread in clinical isolates of Salmonella enterica 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 S. Typhimurium LSP 146/02, a clinical strain selected as representative of the isolates carrying the plasmid, and an otherwise isogenic mutant lacking four genes (fetMP-flsDA) of the fetMP-fls 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 fetMP-flsDA genes was less invasive in cultured epithelial HeLa cells and replicated poorly upon infection of RAW264.7 macrophages. The genes were introduced into S. 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 S. Typhimurium isolates harboring pUO-StVR2.
KW - Epithelial cells invasion
KW - FetMP-Fls system
KW - High-affinity iron uptake systems
KW - Iron-restrictive conditions
KW - Macrophage intracellular replication
KW - Salmonella enterica serovar Typhimurium
U2 - 10.3390/microorganisms8050630
DO - 10.3390/microorganisms8050630
M3 - Journal article
C2 - 32349391
AN - SCOPUS:85084002453
VL - 8
JO - Microorganisms
JF - Microorganisms
SN - 2076-2607
IS - 5
M1 - 630
ER -
ID: 243339907