Evaluation of Staphylococcus aureus Lipoproteins: Role in Nutritional Acquisition and Pathogenicity

Abstract

Bacterial lipoproteins (Lpp) represent a major class of membrane proteins. They are distinguished by a lipid moiety at the N-terminus by which they are anchored either in the outer leaflet of the cytoplasmic membrane or, in Gram-negative bacteria, also in the inner leaflet of the outer membrane. In Gram-positive bacteria Lpp significantly contribute to nutrient transport, Toll-like receptor 2 activation and pathogenicity. Here we examine the Lpp of Staphylococcus aureus USA300, as a prototype for a multiple antibiotic resistant and community-acquired pathogen that is rapidly spreading worldwide. The compiled Lpp were grouped according to the postulated function and dissemination of homologs in the genus Staphylococcus and beyond. Based on this evaluation we also point out Lpp as promising vaccine candidates.

Keywords: S. aureus USA300; Staphylococcus; ion transporters; lipoprotein; lipoprotein dissemination; lipoprotein functions; pathogenicity.

Figure 1

Schematic representation of the functional distribution of the 67 Lpp in S. aureus USA300. The area of the sectors, with the inserted number of Lpp, indicates the proportional distribution. Alone 25 (36%) of the Lpp are involved in ion and nutrient transport, and the ’miscellaneous’ group contains important enzymes and chaperones. USA300 carries relatively high number of 15 (22%) tandem Lpp, to which also the 9 Lpl proteins belong that are encoded by the νSaα genomic island and which play a role in pathogenicity; however, their exact function is still unknown. Finally, the function of 28% of the Lpp is completely unknown.

Figure 2

Classification of the Lpp into four groups based on their similarity and dissemination in bacteria. Each Lpp was blasted against the indicated S. aureus strains and other staphylococcal species representatives. The cut off was ≥40% identity over the entire protein sequence. The colored bar below the listed strains indicates clonal complexes (CC-types) of S. aureus (first half), as well as other staphylococcal species representatives, grouped in semi-pathogenic and non-pathogenic (second half). Group (A) represents Lpp that are highly conserved in the Staphylococcus genus but also in many other genera; an example for this group is YidC, an essential protein in many bacteria. Group (B) represents Lpp that are mainly found in the genus Staphylococcus; the example for this group is PDI, a proposed thioredoxin disulfide-isomerase. Group (C) represents Lpp mainly found in the S. aureus species; an example is the proposed nickel-peptide transporter. Group (D) represents strain-specific Lpp essentially occurring in the strain USA300; the example is an unknown Lpp. The number in front of the gene ID refers to the corresponding numbering in Table 1.

Figure 3

Conserved sequence motif in Lpl and the tandem Lpp. (A) Alignment of the 9 Lpl and the 4 tandem Lpp revealed a core sequence over 38 amino acids with 80% similarity. (B) Sequence alignment of the core region of 15 tandem Lpp by using Clustal Omega program. (C) Phylogenetic tree of the core region of 15 tandem Lpp by using Clustal Omega program.