Regulation of iron transport systems in Enterobacteriaceae in response to oxygen and iron availability

Carpenter, Chandra D.; Payne, Shelley M.

doi:10.1016/j.jinorgbio.2014.01.007

Cited by 78 publications

(55 citation statements)

References 110 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One, or both, of these regulators may control expression of iron transport genes. Having oxygen, as well as iron, regulate iron uptake systems can help protect the cells from oxidative stress and damaging radicals associated with the Fenton reaction in the presence of iron (51). While iron is essential, excess intracellular iron in the presence of oxygen can be lethal (52), and the cell may repress some systems in aerobic environments to reduce potential toxic effects of iron.…”

Section: Discussionmentioning

confidence: 99%

Nonredundant Roles of Iron Acquisition Systems in Vibrio cholerae

et al. 2016

Self Cite

View full text Add to dashboard Cite

Vibrio cholerae, the causative agent of the severe diarrheal disease cholera, thrives in both marine environments and the human host. To do so, it must encode the tools necessary to acquire essential nutrients, including iron, under these vastly different conditions. A number of V. cholerae iron acquisition systems have been identified; however, the precise role of each system is not fully understood. To test the roles of individual systems, we generated a series of mutants in which only one of the four systems that support iron acquisition on unsupplemented LB agar, Feo, Fbp, Vct, and Vib, remains functional. Analysis of these mutants under different growth conditions showed that these systems are not redundant. The strain carrying only the ferrous iron transporter Feo grew well at acidic, but not alkaline, pH, whereas the ferric iron transporter Fbp promoted better growth at alkaline than at acidic pH. A strain defective in all four systems (null mutant) had a severe growth defect under aerobic conditions but accumulated iron and grew as well as the wild type in the absence of oxygen, suggesting the presence of an additional, unidentified iron transporter in V. cholerae. In support of this, the null mutant was only moderately attenuated in an infant mouse model of infection. While the null mutant used heme as an iron source in vitro, we demonstrate that heme is not available to V. cholerae in the infant mouse intestine. The Gram-negative bacterium Vibrio cholerae has an absolute requirement for iron (1). Despite the prevalence of iron within its environmental niches and human host, most of this iron is not readily available. Iron occurs naturally as oxidized (ferric) or reduced (ferrous) iron (2). Ferric iron(III), found in oxygenated environments at neutral to alkaline pH, has very low water solubility and forms large insoluble complexes. Studies of ocean water have found iron to be the limiting nutrient for microbial growth (3). Soluble, ferrous iron(II) is more prevalent under the anoxic conditions that V. cholerae may encounter while colonizing the human host. However, access to iron in the host is limited due to competition with other microbes on host surfaces, as well as sequestration by high-affinity iron-binding host proteins such as transferrin and lactoferrin (4-7). Despite the challenges of obtaining iron in these various environments, V. cholerae is proficient in growth in both marine and host environments.The V. cholerae genome encodes multiple iron acquisition systems, which each transport a specific form of iron and may thus optimize iron acquisition in the various niches that V. cholerae inhabits (8-12). These include genes for the synthesis (vib) and utilization (viu) of vibriobactin, a siderophore that is secreted into the environment, where it binds ferric iron with extremely high affinity (9,(13)(14)(15). Ferrivibriobactin is bound by the outer membrane receptor ViuA (16,17) and is transported across the outer membrane in a process that requires either of two energy transduction systems, To...

show abstract

Section: Discussionmentioning

confidence: 99%

Nonredundant Roles of Iron Acquisition Systems in Vibrio cholerae

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…Iron (Fe) ions serve as metabolic cofactors necessary for crucial processes such as respiration, oxidative stress resistance, and virulence factor production [1]. Iron is able to adopt two stable valences, ferric and ferrous, providing iron-containing proteins with a considerable oxidation-reduction potential [2]. The level of iron required for optimal bacterial growth is~10 −6 M. However, the level of free iron in mammalian tissues is typically~10 −18 M [3].…”

mentioning

confidence: 99%

“…This is because in healthy mammals, iron is mostly found inside cells associated with heme or metalloproteins, or stored in ferritin. Furthermore, the trace amounts of extracellular iron are bound to the high affinity glycoproteins lactoferrin and transferrin [2,3]. During infection, the host immune system withholds Fe from invading pathogens even more stringently in a process called nutritional immunity.…”

mentioning

confidence: 99%

Iron availability and oxygen tension regulate the Yersinia Ysc type III secretion system to enable disseminated infection

et al. 2019

View full text Add to dashboard Cite

The enteropathogen Yersinia pseudotuberculosis and the related plague agent Y. pestis require the Ysc type III secretion system (T3SS) to subvert phagocyte defense mechanisms and cause disease. Yet type III secretion (T3S) in Yersinia induces growth arrest and innate immune recognition, necessitating tight regulation of the T3SS. Here we show that Y. pseudotuberculosis T3SS expression is kept low under anaerobic, iron-rich conditions, such as those found in the intestinal lumen where the Yersinia T3SS is not required for growth. In contrast, the Yersinia T3SS is expressed under aerobic or anaerobic, iron-poor conditions, such as those encountered by Yersinia once they cross the epithelial barrier and encounter phagocytic cells. We further show that the [2Fe-2S] containing transcription factor, IscR, mediates this oxygen and iron regulation of the T3SS by controlling transcription of the T3SS master regulator LcrF. IscR binds directly to the lcrF promoter and, importantly, a mutation that prevents this binding leads to decreased disseminated infection of Y. pseudotuberculosis but does not perturb intestinal colonization. Similar to E. coli, Y. pseudotuberculosis uses the Fe-S cluster occupancy of IscR as a readout of oxygen and iron conditions that impact cellular Fe-S cluster homeostasis. We propose that Y. pseudotuberculosis has coopted this system to sense entry into deeper tissues and induce T3S where it is required for virulence. The IscR binding site in the lcrF promoter is completely conserved between Y. pseudotuberculosis and Y. pestis. Deletion of iscR in Y. pestis leads to drastic disruption of T3S, suggesting that IscR control of the T3SS evolved before Y. pestis split from Y. pseudotuberculosis. Author summaryThe Yersinia type III secretion system (T3SS) is an important virulence factor of the enteropathogen Yersinia pseudotuberculosis as well as Yersinia pestis, the causative agent of PLOS Pathogens | https://doi.

show abstract

“…Higher oxygen levels are associated with the presence of ferric, rather than ferrous, iron. Thus, the presence of oxygen may signal that it would be advantageous to express ferric iron transporters, while anoxic environments may increase the synthesis of ferrous iron transporters (240). Similarly, higher temperatures signal a mammalian host environment and could favor the expression of transporters that acquire iron from host proteins.…”

Section: Other Environmental Sensors and Regulators For Iron Acquisitionmentioning

confidence: 99%

Vibrio Iron Transport: Evolutionary Adaptation to Life in Multiple Environments

Payne

Mey

Wyckoff

2016

Microbiol Mol Biol Rev

Self Cite

102

View full text Add to dashboard Cite

SUMMARYIron is an essential element forVibriospp., but the acquisition of iron is complicated by its tendency to form insoluble ferric complexes in nature and its association with high-affinity iron-binding proteins in the host. Vibrios occupy a variety of different niches, and each of these niches presents particular challenges for acquiring sufficient iron.Vibriospecies have evolved a wide array of iron transport systems that allow the bacteria to compete for this essential element in each of its habitats. These systems include the secretion and uptake of high-affinity iron-binding compounds (siderophores) as well as transport systems for iron bound to host complexes. Transporters for ferric and ferrous iron not complexed to siderophores are also common toVibriospecies. Some of the genes encoding these systems show evidence of horizontal transmission, and the ability to acquire and incorporate additional iron transport systems may have allowedVibriospecies to more rapidly adapt to new environmental niches. While too little iron prevents growth of the bacteria, too much can be lethal. The appropriate balance is maintained in vibrios through complex regulatory networks involving transcriptional repressors and activators and small RNAs (sRNAs) that act posttranscriptionally. Examination of the number and variety of iron transport systems found inVibriospp. offers insights into how this group of bacteria has adapted to such a wide range of habitats.

show abstract

Regulation of iron transport systems in Enterobacteriaceae in response to oxygen and iron availability

Cited by 78 publications

References 110 publications

Nonredundant Roles of Iron Acquisition Systems in Vibrio cholerae

Nonredundant Roles of Iron Acquisition Systems in Vibrio cholerae

Iron availability and oxygen tension regulate the Yersinia Ysc type III secretion system to enable disseminated infection

Vibrio Iron Transport: Evolutionary Adaptation to Life in Multiple Environments

Contact Info

Product

Resources

About