AuxB interacts directly with GpsB and PknB to coordinate cell envelope processes that contribute to intrinsic antibiotic resistance in <i>Staphylococcus aureus</i>

<i>Staphylococcus aureus</i> is a leading cause of fatal infections worldwide. It encodes diverse genes that contribute to the organism's high intrinsic resistance to antibiotics. Understanding the biological roles of these genes and how their features contribute to intrinsic resistance may enable better antibiotic therapies. Here, we investigate AuxB, an intrinsic resistance factor to compounds that target the cell envelope. We find that AuxB interacts directly with the cell cycle regulator GpsB and the eukaryotic-like serine/threonine kinase PknB, another intrinsic resistance factor that is proposed to sense and respond to cell wall status. Based on our findings, we propose that AuxB impacts cell physiology through three mechanisms: (i) by antagonizing PknB's <u>p</u>enicillin-binding protein <u>a</u>nd <u>S</u>er/<u>T</u>hr kinase-<u>a</u>ssociated domain function; (ii) by coordinating the phosphorylation of cell division proteins; and (iii) by forming a homodimer that interacts with GpsB hexamers to enable the formation of extended GpsB interaction networks.