Protective response against Acinetobacter baumannii with ferric iron receptors HemTR-BauA in a murine sepsis model

Abstract

Aim: Iron uptake and metabolism pathways are promising targets in vaccine development as an alternative strategy for antibiotics. Methods and methods: HemTR, a putative heme receptor of Acinetobacter baumannii, was expressed and its protectivity against A. baumannii was determined singly or in combination with the siderophore receptor, BauA, in mice. Results: High level of IgG was elicited. There was a delay in mice mortality with reduced bacterial loads in internal organs in the sublethal challenge. Protection was better in the HemTR-BauA group in both lethal and sublethal challenges. Passive transfer of anti-HemTR and anti-BauA partially protected mice against A. baumannii infection. Conclusion: HemTR in combination with other iron receptors could contribute to the development of protective vaccines against A. baumannii. Acinetobacter baumannii is a dangerous drug-resistant pathogen. One strategy to reduce antibiotic resistance is the use of vaccines. So far, no vaccine has currently been developed against A. baumannii. Iron is a transition metal that is essential for pathogen growth and the successful colonization of a host. A. baumannii has developed various ways to scavenge iron from its host and these generally rely on iron receptors that bind specially to a wide range of iron-containing molecules named siderophores or heme. Iron receptors are attractive targets for therapeutic intervention. They are the first gate for iron transport into bacterial cells. In this study, we predicted a heme receptor named hemTR, as a vaccine candidate through bioinformatic analysis and determined its protective efficacy in mice against A. baumannii infection with and without BauA, a siderophore receptor. The results showed that the combination of heme and siderophore receptors is a better formulation for protection against A. baumannii infection. The findings indicate that a vaccine strategy based on iron pathways could be a potential treatment approach.