Synergetic attenuated inflammatory response and increased apoptosis confer high pathogenicity of Acinetobacter baumannii.

Acinetobacter baumannii (A. baumannii) has emerged as a major global healthcare threat, ranking among the leading causes of both hospital-acquired and community-acquired infections. Its extensive antibiotic resistance complicates treatment, underscoring the need for therapeutic targets that elicit robust immune responses. This study identified two multidrug-resistant clinical strains of A. baumannii A.ba-R (rough) and A.ba-S (smooth). A.ba-R has thick and dense capsular polysaccharide, and exhibits high pathogenicity by suppressing host inflammatory responses and inducing apoptosis to evade immune surveillance. Conversely, A.ba-S possesses a thin capsular polysaccharide and triggers pyroptosis via inflammasome activation, causing pronounced inflammation. RNA-sequencing revealed that capsule polysaccharide, transmembrane secretion systems, and nutrient acquisition systems of A.ba-R might contribute to the induction of apoptosis. Our study reveals different roles of apoptosis and pyroptosis in the pathogenicity of A. baumannii and provides potential therapeutic targets against A. baumannii infections.