7xli
Crystal structure of IsdB linker-NEAT2 bound to a nanobody (VHH)
Structural highlights
FunctionISDB_STAAM Cell wall-anchored surface receptor that extracts heme from oxidized metHb to enable growth on hemoglobin as a sole iron source. Rapidly extracts heme from hemoglobin and transfers it to IsdA or IsdC, which then relays it to the membrane transporter/IsdEF for internalization. Promotes also resistance to hydrogen peroxide and killing by neutrophils.[UniProtKB:A6QG30] Publication Abstract from PubMedMethicillin-resistant Staphylococcus aureus, or MRSA, is one of the major causative agents of hospital-acquired infections worldwide. Novel antimicrobial strategies efficient against antibiotic-resistant strains are necessary and not only against S. aureus. Among those, strategies that aim at blocking or dismantling proteins involved in the acquisition of essential nutrients, helping the bacteria to colonize the host, are intensively studied. A major route for S. aureus to acquire iron from the host organism is the Isd (iron surface determinant) system. In particular, the hemoglobin receptors IsdH and IsdB located on the surface of the bacterium are necessary to acquire the heme moiety containing iron, making them a plausible antibacterial target. Herein, we obtained an antibody of camelid origin that blocked heme acquisition. We determined that the antibody recognized the heme-binding pocket of both IsdH and IsdB with nanomolar order affinity through its second and third complementary-determining regions. The mechanism explaining the inhibition of acquisition of heme in vitro could be described as a competitive process in which the complementary-determining region 3 from the antibody blocked the acquisition of heme by the bacterial receptor. Moreover, this antibody markedly reduced the growth of three different pathogenic strains of MRSA. Collectively, our results highlight a mechanism for inhibiting nutrient uptake as an antibacterial strategy against MRSA. Targeting hemoglobin receptors IsdH and IsdB of Staphylococcus aureus with a single VHH antibody inhibits bacterial growth.,Valenciano-Bellido S, Caaveiro JMM, Nakakido M, Kuroda D, Aikawa C, Nakagawa I, Tsumoto K J Biol Chem. 2023 Sep;299(9):104927. doi: 10.1016/j.jbc.2023.104927. Epub 2023 , Jun 15. PMID:37330175[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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