2026-10-14T23:09:37Z https://www.scidb.cn/oai

10.57760/sciencedb.37744 2026-06-01T17:46:19Z

2026-06-01 SRPX2 Regulates Macrophage Antibacterial Defense via the PI3K/AKT–NOX2–ROS–LAP Pathway During Staphylococcus aureus Infection doi:10.57760/sciencedb.37744 en Staphylococcus aureus (S. aureus) is a prevalent pathogen responsible for a spectrum of infections, ranging from superficial skin infections to life-threatening illnesses such as bacteremia and sepsis. Methicillin-resistant S. aureus (MRSA) strains remain a critical clinical threat due to their broad antibiotic resistance, highlighting an urgent demand for innovative therapeutic strategies. In this study, we identified Sushi repeat-containing protein X-linked 2 (SRPX2) as a novel regulator governing macrophage antibacterial defense. Our results demonstrate that SRPX2 is rapidly upregulated upon S. aureus infection and functions as an upstream activator of the PI3K/AKT signaling cascade. This signaling axis is essential for NOX2 activation and the subsequent generation of reactive oxygen species (ROS), which further facilitate LC3-associated phagocytosis (LAP), a non-canonical autophagy pathway indispensable for efficient bacterial clearance. SRPX2 deficiency compromises ROS production and LAP activation, thereby promoting intracellular bacterial survival and underscoring the pivotal role of SRPX2 in macrophage antimicrobial defense. Furthermore, pharmacological activation of AKT was found to rescue the functional defects caused by SRPX2 deficiency, restoring NOX2 expression and bacterial killing capacity. These findings establish a definitive functional linkage among SRPX2, the PI3K/AKT pathway, NOX2, and ROS-mediated antimicrobial responses. Collectively, this study provides novel insights into host-pathogen interactions and indicates that SRPX2 holds great potential as a therapeutic target to augment host defense against MRSA infections. Staphylococcus aureus; ROS; LC3-associated phagocytosis; Host-pathogen interaction; Macrophage qiyuan jin yaxuan zhai rui qiang qi chen jijie li jinqi zhong mingxiao han yi wang jing yang jiayi tang chenhao zhao hong du haifang zhang EMBARGO https://creativecommons.org/licenses/by-nc-nd/4.0/ dataset Science Data Bank