Evaluation of the Stereochemistry of Staphyloferrin A for Developing Staphylococcus‐Specific Targeting Conjugates

Abstract

AbstractBacteria in the genus Staphylococcus are pathogenic and harmful to humans. Alarmingly, some Staphylococcus, such as methicillin‐resistant S. aureus (MRSA) and vancomycin‐resistant S. aureus (VRSA) have spread worldwide and become notoriously resistant to antibiotics, threatening and concerning public health. Hence, the development of new Staphylococcus‐targeting diagnostic and therapeutic agents is urgent. Here, we chose the S. aureus‐secreted siderophore staphyloferrin A (SA) as a guiding unit. We developed a series of Staphyloferrin A conjugates (SA conjugates) and showed the specific targeting ability to Staphylococcus bacteria. Furthermore, among the structural factors we evaluated, the stereo‐chemistry of the amino acid backbone of SA conjugates is essential to efficiently target Staphylococci. Finally, we demonstrated that fluorescent Staphyloferrin A probes (SA‐FL probes) could specifically target Staphylococci in complex bacterial mixtures.