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The remaining Fe is found in other proteins, such as iron-sulfur cluster enzymes, Fe-chelating proteins (Tf and Lf), and a pool of accessible Fe ions called the labile Fe pool (LIP), all of them constitutes the iron-containing proteins involved in metabolic pathways from hosts. Inside the human body the solubility of iron is extremely low, because the Fe exists in insoluble mineral complexes, or under aerobic, aqueous, and neutral pH conditions, that difficult the access of bacteria to this element. Besides, Fe is bound to mammalian high-affinity iron-binding proteins such as Tf, Lf, and Ft and in consequence, many bacteria have developed high-affinity Fe transport systems to acquire Fe from sources in their niches (Rangel et al., 2008; Jin et al., 2009; Tanabe et al., 2012). The Fe sources available in the different environmental niches of V. parahaemolyticus are selleck kinase inhibitor described and discussed in Figure ?Figure11. FIGURE 1 Iron sources available in the environmental niches of Vibrio parahaemolyticus. V. parahaemolyticus is an obligate halophilic organism, meaning that it requires salt to live. This organism is naturally occurring and found worldwide. It can commonly be ... Role of Iron in the Virulence of Vibrio parahaemolyticus Iron regulates virulence factors of V. parahaemolyticus and almost all pathogenic bacteria. Inside a host the Fe concentration is very low, so many pathogens uses this (low-iron conditions) for inducing expression of genes involved in the virulence (Litwin and Calderwood, 1993). The presence of ferric Fe in bacterial growth media has been found to increase the adherence intensities of virulent V. parahaemolyticus strains to human fetal intestinal (HFI) cells in vitro (Hackney et al., 1980). Intraperitoneally injection with V. parahaemolyticus in the presence of ferric ammonium citrate in mice increased the bacterial proliferation, thus enhancing the lethality toward infected mice. V. parahaemolyticus cultures in low-iron conditions showed better proliferation than iron-rich cultures in response to the addition of supplementary Fe. Also, the production of thermostable direct toxin (TDH) by the hemolytic strains of V. parahaemolyticus was higher in iron-limited cultures than in iron-rich cultures, though the production of TDH by both iron-limited and iron-rich cultures was inhibited by the addition of Fe. In conclusion, the enhancement of V. parahaemolyticus virulence in the model mice likely occurred through the increase of bacterial proliferation in vivo and not the stimulation of TDH production. The V. parahaemolyticus precultured under iron-limited conditions may be more adaptable to the in vivo environment (Wong and Lee, 1994; Funahashi et al., 2003; Gode-Potratz et al., 2010). The effect of lysed blood on the virulence of V.