Divalent metal ions in microbial microenvironment and metalloenzyme metal centers

Divalent metal ions, such as zinc, iron, and manganese, are essential components of the microbial microenvironment and serve as critical cofactors for a wide array of metalloenzymes (Hood & Skaar, 2012). These ions are vital for microbial survival, participating in DNA synthesis, metabolic pathways, and defense against host-generated reactive oxygen species. In response to infection, the host immune system utilizes a strategy known as nutritional immunity to sequester these metals, effectively starving the invading pathogens (Skaar, 2010). Microbial metalloenzymes, particularly metallo-beta-lactamases, represent a significant clinical challenge as they confer resistance to broad-spectrum antibiotics like carbapenems (Bush, 2013). Therapeutic interventions targeting these metal centers typically involve chelating agents that strip the metal from the enzyme or small molecules that coordinate with the metal to block the active site (King et al., 2014). While promising, these strategies must overcome the hurdle of selectivity to avoid inhibiting essential human metalloenzymes, such as matrix metalloproteinases or angiotensin-converting enzyme.

Other names

Metalloenzyme metal centersMicrobial divalent metal ionsMetal-dependent microbial enzymes

Inhibition of microbial growth or enzyme activity through the sequestration or coordination of essential divalent metal ions.