Acinetobacter baumannii: Virulence Strategies and Host Defense Mechanisms

Abstract

Acinetobacter baumannii is a highly antibiotic-resistant bacterial pathogen known to cause severe life-threatening infections, including pneumonia, meningitis, and sepsis. Recent emergence of this bacterium as a serious nosocomial pathogen has led to categorization of A. baumannii as a "high-priority" pathogen by the World Health Organization (WHO), for which research efforts are urgently required to develop therapeutic interventions. Some of the properties that make A. baumannii a serious pathogen include its capacity to tolerate high levels of stress and enhanced expression of efflux pumps that enable high degrees of antibiotic resistance. Virulence mechanisms employed by A. baumannii to establish successful infection and host responses elicited against A. baumannii to counter the infection are discussed in detail in this article.

Keywords: Acinetobacter baumannii; bacterial infection; host immune responses; inflammation; virulence mechanisms.

FIG. 1.

Acinetobacter baumannii secretes OMVs containing OmpA that induce mitochondrial damage. Cytotoxic OMVs containing OmpA are secreted by A. baumannii, which deliver OmpA to mitochondria. OmpA induces fragmentation of the mitochondrial network driven by the host protein DRP1, which is the master regulator of mitochondrial fission. OmpA-mediated mitochondrial fragmentation is accompanied with enhanced ROS levels, decreased ATP levels, and increased mitochondrial depolarization. OmpA-mediated damage to host cell mitochondria also leads to the release of the mitochondrial protein cytochrome C. Release of cytochrome C induces apoptotic cell death in host cells. Figure created with BioRender.com. OMVs, outer membrane vesicles; ROS, reactive oxygen species.

FIG. 2.

Host responses against A. baumannii. Infection with A. baumannii activates the plasma membrane-bound TLR4 and the endosome-bound TLR9. Activated TLR signaling leads to the activation and nuclear translocation of the transcription factor NF-κB. Intracellular A. baumannii also contributes to NF-κB activation through the intracellular PRRs—NOD1 and NOD2. Activated NF-κB drives the expression of proinflammatory cytokines, including TNF, and IL-6 and IL-8. NF-κB also stimulates the expression of AMPs like human β-defensins, which restrict A. baumannii growth. Figure created with BioRender.com. AMPs, antimicrobial peptides; IL, interleukin; PRRs, pathogen recognition receptors; TLR, toll-like receptor; TNF, tumor necrosis factor.