Pseudomonas spp. growing in a multi-well plate produce differently colored pigments (red, yellow and green). The yellow greenish pyoverdines are strong iron chelators with antibacterial properties against several human pathogens. Image credit: Vera Vollenweider (CC BY 4.0)
Despite the wide range of available antibiotics, a majority work through a similar mechanism, which enables some bacteria to become resistant to medical treatment. This means that the effectiveness of these molecules goes down and many curable infections may no longer be treatable.
Collectively, antibiotic resistance poses a similar threat as other major diseases, such as malaria. One promising approach for discovering new antibiotics is to explore natural microbial communities for their ability to produce secondary metabolites with antimicrobial properties. Such metabolites are typically secreted by bacteria to compete with other community members for essential resources including nutrients.
A well-known group of secreted metabolites are siderophores, which tightly sequester iron, a critical nutrient for bacterial growth. Each bacterial species produces its own set of specific siderophores, thus leading to a severe competition for iron.
Vollenweider et al. investigated whether a group of siderophores secreted by Pseudomonas bacteria, called pyoverdines, are an effective antimicrobial agent against harmful human pathogens. Pyoverdines have a high affinity to iron and prevent competing bacteria from accessing the critical nutrient. This can inhibit their growth by starving them of iron.
Vollenweider et al. treated resistant pathogens like Acinetobacter, Klebsiella and Staphylococcus grown in the laboratory, and found that pyoverdines significantly reduce their growth without the bacteria acquiring resistance. To test whether this treatment would work in a living infected animal, the group administered pyoverdines to moth larvae infected with the same pathogens and observed increased survival rates in the host.
As iron is also required for human metabolism and found in the haemoglobin of red blood cells, Vollenweider, et al. confirmed pyoverdines do not retrieve iron from haemoglobin. Finally, in laboratory settings, pyoverdines did not negatively affect the growth of a human and a mouse cell line at low concentrations strong enough to inhibit the growth of pathogens.
This approach is a promising example of adopting natural mechanisms that can have antimicrobial properties, and siderophores, in particular pyoverdines, may become a useful tool to treat otherwise incurable infections. Further research is needed in living mammalian models to confirm efficacy and safety of this novel antimicrobial treatment.
