Probiotic Bacteria Reduce Salmonella Typhimurium Intestinal Colonization by Competing for Iron

Deriu, Elisa; Liu, Janet Z.; Pezeshki, Milad; Edwards, Robert A.; Ochoa, Roxanna J.; Contreras, Heidi; Libby, Stephen J.; Fang, Ferric C.; Raffatellu, Manuela

doi:10.1016/j.chom.2013.06.007

Cited by 401 publications

(348 citation statements)

References 52 publications

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“…The importance of iron in host-pathogen interactions has been well documented (47,48,49,50,51). Several recent reports also highlighted the significance of iron acquisition during Salmonella infection (mostly through genetic studies) (52,53,54).…”

Section: Discussionmentioning

confidence: 99%

Proteomic Analyses of Intracellular Salmonella enterica Serovar Typhimurium Reveal Extensive Bacterial Adaptations to Infected Host Epithelial Cells

Liu

Zhang

et al. 2015

Infect Immun

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Salmonella species can gain access into nonphagocytic cells, where the bacterium proliferates in a unique membrane-bounded compartment. In order to reveal bacterial adaptations to their intracellular niche, here we conducted the first comprehensive proteomic survey of Salmonella isolated from infected epithelial cells. Among ϳ3,300 identified bacterial proteins, we found that about 100 proteins were significantly altered at the onset of Salmonella intracellular replication. In addition to substantially increased iron-uptake capacities, bacterial high-affinity manganese and zinc transporters were also upregulated, suggesting an overall limitation of metal ions in host epithelial cells. We also found that Salmonella induced multiple phosphate utilization pathways. Furthermore, our data suggested upregulation of the two-component PhoPQ system as well as of many downstream virulence factors under its regulation. Our survey also revealed that intracellular Salmonella has increased needs for certain amino acids and biotin. In contrast, Salmonella downregulated glycerol and maltose utilization as well as chemotaxis pathways. While infectious diseases continue to be a major threat to human health, there is an urgent need in rational design and development of new treatment strategies. As a model for studying bacterial pathogenesis, Salmonella spp. cause millions of infections per year ranging from food poisoning to life-threatening systemic typhoid fever (1). Central to its pathogenesis is a syringelike structure known as the type III secretion system (T3SS), which delivers bacterial proteins called effectors directly into eukaryotic host cells (2, 3). The injected proteins are able to modulate various host cellular functions, and over the years extensive studies have been carried out on these effector proteins and/or their interacting host targets. While these studies have contributed substantially to our initial understanding of infection biology, daunting challenges are encountered because conventional reductionism-based studies certainly cannot explain the complex multifactorial nature of host-pathogen interactions (4). Systems-level analyses can provide a panoramic view of the functional host-pathogen interplay and thus are promising in this regard.During infection, the intracellular environment is likely to be very different from what bacteria encounter in rich culture media. It has long been known that various nutritional and environmental differences within host cells force bacterial pathogens to reprogram their gene expression. In fact, transcriptomic studies of intracellular Salmonella within infected macrophages and epithelial cells contributed to our initial understanding of bacterial adaptations in the host environment (5, 6). Because proteins are the final gene products and their changes may not correlate with those of mRNA, direct readout of the bacterial proteome is highly desired. Such measurements, however, have been technically challenging due to the presence of vast amounts of host proteins (7). As a ...

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Section: Discussionmentioning

confidence: 99%

Proteomic Analyses of Intracellular Salmonella enterica Serovar Typhimurium Reveal Extensive Bacterial Adaptations to Infected Host Epithelial Cells

Liu

Zhang

et al. 2015

Infect Immun

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“…For instance, commensal bacteria such as Escherichia coli strain Nissle 1917 may outcompete and reduce Salmonella enterica sv. Typhimurium colonization due to their iron uptake capacities (Deriu et al, 2013). Another example is the occupation of two distinct nutritional niches by E. coli strains HS and Nissle 1917 which together consume five sugars that are also important for the colonization of streptomycin-treated mice by pathogenic E. coli (Maltby et al, 2013).…”

Section: Gut Microbiotamentioning

confidence: 99%

From food to cell: nutrient exploitation strategies of enteropathogens

Staib

Fuchs

2014

Microbiology

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Upon entering the human gastrointestinal tract, foodborne bacterial enteropathogens encounter, among numerous other stress conditions, nutrient competition with the host organism and the commensal microbiota. The main carbon, nitrogen and energy sources exploited by pathogens during proliferation in, and colonization of, the gut have, however, not been identified completely. In recent years, a huge body of literature has provided evidence that most enteropathogens are equipped with a large set of specific metabolic pathways to overcome nutritional limitations in vivo, thus increasing bacterial fitness during infection. These adaptations include the degradation of myo-inositol, ethanolamine cleaved from phospholipids, fucose derived from mucosal glycoconjugates, 1,2-propanediol as the fermentation product of fucose or rhamnose and several other metabolites not accessible for commensal bacteria or present in competition-free microenvironments. Interestingly, the data reviewed here point to common metabolic strategies of enteric pathogens allowing the exploitation of nutrient sources that not only are present in the gut lumen, the mucosa or epithelial cells, but also are abundant in food. An increased knowledge of the metabolic strategies developed by enteropathogens is therefore a key factor to better control foodborne diseases.

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“…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)(5)(6)(7). Despite the challenges of obtaining iron in these various environments, V. cholerae is proficient in growth in both marine and host environments.…”

mentioning

confidence: 99%

Nonredundant Roles of Iron Acquisition Systems in Vibrio cholerae

et al. 2016

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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...

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Probiotic Bacteria Reduce Salmonella Typhimurium Intestinal Colonization by Competing for Iron

Cited by 401 publications

References 52 publications

Proteomic Analyses of Intracellular Salmonella enterica Serovar Typhimurium Reveal Extensive Bacterial Adaptations to Infected Host Epithelial Cells

Proteomic Analyses of Intracellular Salmonella enterica Serovar Typhimurium Reveal Extensive Bacterial Adaptations to Infected Host Epithelial Cells

From food to cell: nutrient exploitation strategies of enteropathogens

Nonredundant Roles of Iron Acquisition Systems in Vibrio cholerae

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