The Mechanisms of Disease Caused by Acinetobacter baumannii

Abstract

Acinetobacter baumannii is a Gram negative opportunistic pathogen that has demonstrated a significant insurgence in the prevalence of infections over recent decades. With only a limited number of "traditional" virulence factors, the mechanisms underlying the success of this pathogen remain of great interest. Major advances have been made in the tools, reagents, and models to study A. baumannii pathogenesis, and this has resulted in a substantial increase in knowledge. This article provides a comprehensive review of the bacterial virulence factors, the host immune responses, and animal models applicable for the study of this important human pathogen. Collating the most recent evidence characterizing bacterial virulence factors, their cellular targets and genetic regulation, we have encompassed numerous aspects important to the success of this pathogen, including membrane proteins and cell surface adaptations promoting immune evasion, mechanisms for nutrient acquisition and community interactions. The role of innate and adaptive immune responses is reviewed and areas of paucity in our understanding are highlighted. Finally, with the vast expansion of available animal models over recent years, we have evaluated those suitable for use in the study of Acinetobacter disease, discussing their advantages and limitations.

Keywords: A. baumannii; animal models; bacterial virulence factors; host-pathogen interactions; immune response.

Figure 1

Bacterial virulence factors. Schematic of the bacterial cell envelope depicting some of the known virulence factors, including OmpA, the Type II, IV, and V secretion systems, phospholipase D (PLD), iron acquisition systems (Acinetobactin and FecA), the inner membrane two-component system, GacAS and extracellular factors, including lipid oligosaccharide, capsular polysaccharide, and outer membrane vesicles. For simplicity, peptidoglycan has been excluded and individual components are not to scale.

Figure 2

Immune responses to Acinetobacter. Immune cells involved in the clearance of Acinetobacter infections are denoted on the right-hand side, with an insert depicting the cellular components responsible. The toll-like receptor (TLR) 2 and 4 signaling leads to activation of NFĸB via MyD88, resulting in transcriptional activation and the synthesis of a range of cytokines and chemokines. Other cytoplasmic proteins shown to be involved in response to Acinetobacter infection are highlighted, with TLR9 localized to the endosome, in conjugation with reactive oxygen species (ROS) and nitric oxide (NO). Extracellular components, including cationic and anionic antimicrobial peptides, antibodies, and C3 complement are depicted left to right. For simplicity, not all proteins involved in the TLR signaling pathways are depicted and individual components are not to scale.