Acinetobacter: an emerging pathogen with a versatile secretome

Abstract

Acinetobacter baumannii is a notorious pathogen that has emerged as a healthcare nightmare in recent years because it causes serious infections that are associated with high morbidity and mortality rates. Due to its exceptional ability to acquire resistance to almost all available antibiotics, A. baumannii is currently ranked as the first pathogen on the World Health Organization's priority list for the development of new antibiotics. The versatile range of effectors secreted by A. baumannii represents a large proportion of the virulence arsenal identified in this bacterium to date. Thus, these factors, together with the secretory machinery responsible for their extrusion into the extracellular milieu, are key targets for novel therapeutics that are greatly needed to combat this deadly pathogen. In this review, we provide a comprehensive, up-to-date overview of the organization and regulatory aspects of the Acinetobacter secretion systems, with a special emphasis on their versatile substrates that could be targeted to fight the deadly infections caused by this elusive pathogen.

Fig. 1. Schematic representation of extensively studied secretion systems in Acinetobacter species, showing their general architecture, membrane components, and the most important effectors.

T6SS effectors are vgrG-associated and are encoded by genes that are in close proximity to each of the four vgrG genes identified in A. baumannii. The VgrG1-associated, VgrG2-associated, and VgrG4-associated effectors are type VI lipase effector (Tle), a type VI DNAse effector (Tde), and a peptidoglycan-targeting type VI amidase effector (Tae), respectively. The VgrG3 type VI effector (Tse) does not possess characteristic functional domains and is predicted to have a role in bacterial killing. A large number of T2SS effectors have been identified, including the verified lipolytic enzymes LipAN, LipH, and the chaperone-dependent LipA (chaperone LipB), in addition to chaperone-dependent CpaA metallopeptidase (chaperone CpaB). More than 20 other predicted T2SS effectors are yet to be verified as true substrates. Two T5SS subtypes have been identified in A. baumannii, the Acinetobacter trimeric autotransporter (Ata) and the two-partner secretion (TPS) system AbFhaB/FhaC, which plays a role in cellular adhesion. Both the T2SS and T5SS depend on the Sec machinery for the translocation of substrates across the inner cytoplasmic membrane (IM). In addition, A. baumannii possesses a homolog of the TolC-HlyB-D T1SS, which secretes a hemolysin-like RTX protein and a Bap-like protein important for biofilm formation