Abstract
Acinetobacter baumannii is a multidrug-resistant pathogen that represents a serious threat to global health. A. baumannii possesses a wide range of virulence factors that contribute to the bacterial pathogenicity. Among them, the siderophore acinetobactin is one of the most important, being essential for the development of the infection. In this study we performed an in-depth analysis of the acinetobactin cluster in the strain A. baumannii ATCC 17978. For this purpose, nineteen individual isogenic mutant strains were generated, and further phenotypical analysis were performed. Individual mutants lacking the biosynthetic genes entA, basG, basC, basD, and basB showed a significant loss in virulence, due to the disruption in the acinetobactin production. Similarly, the gene bauA, coding for the acinetobactin receptor, was also found to be crucial for the bacterial pathogenesis. In addition, the analysis of the ΔbasJ/ΔfbsB double mutant strain demonstrated the high level of genetic redundancy between siderophores where the role of specific genes of the acinetobactin cluster can be fulfilled by their fimsbactin redundant genes. Overall, this study highlights the essential role of entA, basG, basC, basD, basB and bauA in the pathogenicity of A. baumannii and provides potential therapeutic targets for the design of new antivirulence agents against this microorganism.
Highlights
Acinetobacter baumannii is one of the most common nosocomial pathogens responsible for a wide range of concerning diseases, such as pneumonia, bacteremia or secondary meningitis (Wong et al, 2017)
The eleven mutant strains lacking the genes involved in the biosynthesis of acinetobactin were classified in three different groups: (i) genes involved in the synthesis of the dihydroxybenzoic acid (DHBA) precursor, (ii) genes involved in the synthesis of the N-hydroxyhistamine precursor and (iii) genes involved in the modification and assembly of the acinetobactin precursors into the final molecule (Figure 1A)
Our results showed that the genes basG and basC, involved in the biosynthesis of the N-hydroxyhistamine precursor, and the genes basD and basB, involved in the assembly of the precursors, are essential for the biosynthesis of acinetobactin and they are crucial for the virulence of A. baumannii in vivo
Summary
Acinetobacter baumannii is one of the most common nosocomial pathogens responsible for a wide range of concerning diseases, such as pneumonia, bacteremia or secondary meningitis (Wong et al, 2017). The main characteristic of this pathogen is its ability to acquire new antimicrobial resistance, it shows several mechanisms involved in virulence, persistence and stress adaptation that enhance its pathogenicity (Harding et al, 2018). Within this context, many researchers have focused their efforts in developing alternatives to conventional antibiotics, such as antivirulence agents, that can work alone or together with antibiotics to overcome A. baumannii infections (Dickey et al, 2017). The expression of fimsbactins was shown to be enough to support the growth of
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