Acquisition of Mn(II) in Addition to Fe(II) Is Required for Full Virulence of Salmonella enterica Serovar Typhimurium Original paper

What was studied?

This study explored the role of manganese (Mn) and iron (Fe) acquisition in the virulence of Salmonella enterica serovar Typhimurium. The research focused on the genes involved in the transport of these metals, namely mntH (a manganese transporter), sitABCD (an ABC transporter for both Mn and Fe), and feoB (a ferrous iron transporter), and their impact on the bacterium’s ability to survive and replicate inside host macrophages, as well as its virulence in vivo.

Who was studied?

The study primarily focused on Salmonella enterica serovar Typhimurium and its ability to acquire divalent metal ions, specifically manganese and iron, during infection. The study utilized various mutant strains of S. Typhimurium that were deficient in mntH, sitABCD, and feoB to assess their roles in bacterial survival, replication, and virulence in both in vitro macrophage models and in vivo mouse models.

What were the most important findings?

The study demonstrated that both manganese and iron acquisition are essential for the full virulence of Salmonella enterica serovar Typhimurium. The sitABCD operon, responsible for the high-affinity transport of Mn(II) and Fe(II), was crucial for the bacterium’s ability to infect and survive in mice, particularly in macrophages. Mutants deficient in sitABCD exhibited reduced Mn(II) uptake, increased sensitivity to hydrogen peroxide (H2O2), and were significantly attenuated in vivo, showing prolonged survival times in infected mice. The feoB mutant, which lacked the Fe(II) transporter, also showed impaired virulence, though it had minimal effects on metal uptake in vitro. In contrast, the mntH mutation had a less significant impact on virulence, suggesting that while mntH contributes to Mn(II) uptake, it is not as critical for virulence as sitABCD. Additionally, combining mutations in mntH, sitABCD, and feoB led to further attenuation, underscoring the non-redundant roles of these transporters in acquiring essential metals for infection. The study also highlighted that the Nramp1 protein, which is involved in metal ion efflux in macrophages, plays a key role in limiting Salmonella replication by sequestering Mn(II).

What are the greatest implications of this study?

The findings underscore the critical role of metal acquisition, particularly manganese and iron, in bacterial pathogenesis. Understanding the mechanisms behind Salmonella‘s ability to acquire these metals could pave the way for developing novel therapeutic strategies that target metal transport systems in pathogenic bacteria. By disrupting these transporters, it may be possible to impair bacterial growth and survival within the host, enhancing the immune response and reducing the ability of Salmonella to establish infection. Furthermore, the study provides insights into how pathogens adapt to host-imposed metal restrictions and how these adaptations contribute to virulence, offering valuable information for clinicians dealing with Salmonella infections and potentially other metal-dependent bacterial pathogens.