<i>Acinetobacter baumannii</i> Strains Deficient in the Clp Chaperone-Protease Genes Have Reduced Virulence in a Murine Model of Pneumonia

• Main Authors: J Christian Belisario, Hiu Ham Lee, Harshani Luknauth, Nathan W. Rigel, Luis R. Martinez
• Format: Article
• Language: English
• Published: MDPI AG 2021-02-01
• Series: Pathogens
• Subjects: <i>A. baumannii</i>; biofilms; Clp-protease; infection; macrophages; pneumonia
• Online Access: https://www.mdpi.com/2076-0817/10/2/204

<i>Acinetobacter baumannii</i> has emerged as a significant opportunistic Gram-negative pathogen and causative agent of nosocomial pneumonia especially in immunocompromised individuals in intensive care units. Recent advances to understand the contribution and function of <i>A. baumannii</i> virulence factors in its pathogenesis have begun to elucidate how this bacterium interacts with immune cells and its interesting mechanisms for multi-antibiotic resistance. Taking advantage of the availability of the <i>A. baumannii</i> AB5075 transposon mutant library, we investigated the impact of the <i>A. baumannii</i> Clp genes, which encode for a chaperone-protease responsible for the degradation of misfolded proteins, on bacterial virulence in a model of pneumonia using C57BL/6 mice and survival within J774.16 macrophage-like cells. Clp-protease <i>A. baumannii</i> mutants exhibit decreased virulence in rodents, high phagocytic cell-mediated killing and reduced biofilm formation. Capsular staining showed evidence of encapsulation in <i>A. baumannii</i> AB5075 and Clp-mutant strains. Surprisingly, <i>clpA</i> and <i>clpS</i> mutants displayed irregular cell morphology, which may be important in the biofilm structural deficiencies observed in these strains. Interestingly, <i>clpA</i> showed apical-like growth, proliferation normally observed in filamentous fungi. These findings provide new information regarding <i>A. baumannii</i> pathogenesis and may be important for the development of therapies intended at reducing morbidity and mortality associated with this remarkable pathogen.