title: The secretome of Acinetobacter baumannii ATCC 17978 type II secretion system reveals a novel plasmid encoded phospholipase that could be implicated in lung colonization.
abstract: Acinetobacter baumannii infections are compounded with a striking lack of treatment options. In many Gram-negative bacteria, secreted proteins play an important early role in avoiding host defences. Typically, these proteins are targeted to the external environment or into host cells using dedicated transport systems. Despite the fact that medically relevant species of Acinetobacter possess a type II secretion system (T2SS), only recently, its significance as an important pathway for delivering virulence factors has gained attention. Using in silico analysis to characterize the genetic determinants of the T2SS, which are found clustered in other organisms, in Acinetobacter species, they appear to have a unique genetic organization and are distributed throughout the genome. When compared to other T2SS orthologs, individual components of the T2SS apparatus showed the highest similarity to those of Pseudomonas aeruginosa. A mutant of Acinetobacter baumannii strain ATCC 17978 lacking the secretin component of the T2SS (ΔgspD), together with a trans-complemented mutant, were tested in a series of in vitro and in vivo assays to determine the role of T2SS in pathogenicity. The ΔgspD mutant displayed decreased lipolytic activity, associated with attenuated colonization ability in a murine pneumonia model. These phenotypes are linked to LipAN, a novel plasmid-encoded phospholipase, identified through mass spectroscopy as a T2SS substrate. Recombinant LipAN showed specific phospholipase activity in vitro. Proteomics on the T2-dependent secretome of ATCC 17978 strain revealed its potential dedication to the secretion of a number of lipolytic enzymes, among others which could contribute to its virulence. This study highlights the role of T2SS as an active contributor to the virulence of A. baumannii potentially through secretion of a newly identified phospholipase.
authors.affiliation: Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Noha M
authors.initials: NM
authors.lastname: Elhosseiny
authors.affiliation: Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt.
authors.forename: Ossama M
authors.initials: OM
authors.lastname: El-Tayeb
authors.affiliation: Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt.
authors.forename: Aymen S
authors.initials: AS
authors.lastname: Yassin
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Lory
authors.affiliation: Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt. Electronic address: ahmed.s.attia@staff.cu.edu.eg.
authors.forename: Ahmed S
authors.initials: AS
authors.lastname: Attia
mesh_terms: D000151:Acinetobacter Infections / Q000382:microbiology* / Q000473:pathology; D040981:Acinetobacter baumannii / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D017353:Gene Deletion; D023061:Gene Order; D005798:Genes, Bacterial; D005816:Genetic Complementation Test; D008168:Lung / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010740:Phospholipases / Q000378:metabolism*; D010957:Plasmids; D018410:Pneumonia, Bacterial / Q000382:microbiology* / Q000473:pathology; D021381:Protein Transport; D011550:Pseudomonas aeruginosa / Q000235:genetics; D000069178:Type II Secretion Systems / Q000235:genetics / Q000378:metabolism*; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: D000069178:Type II Secretion Systems; D037521:Virulence Factors; D010740:Phospholipases
keywords: A. baumannii; Phospholipase; T2SS; Virulence