genomewide characterization of host-pathogen interactions by ...

Maren Depke
Introduction
STAPHYLOCOCCUS AUREUS
General Features of S. aureus
Staphylococci are Gram-positive bacteria of approximately 1 µm diameter, which often
aggregate in grape-like structures. The golden color of Staphylococcus aureus colonies – derived
from staphyloxanthin and other C 30 triterpenoid carotenoids (Marshall/Wilmoth 1981) which
function as antioxidant protection molecules (Liu GY et al. 2005) – led to its naming. Several
S. aureus properties like the ability to perform hemolysis and expression of catalase and
coagulase allow differentiation of the species from other bacteria. S. aureus can produce energy
by aerobic respiration, but is facultatively able to survive in anaerobic environments. In situations
without oxygen it can apply lactate fermentation. S. aureus seems to be naturally auxotrophic
and requires e. g. amino acids as growth supplement. The staphylococcal cell wall peptidoglycan
features a special crossbridge structure formed by multiple glycine residues. These are the target
structures for lysostaphin, a staphylocidal enzyme from Staphylococcus simulans first described
by Schindler and Schuhardt in 1964, which was taken over by scientist for several laboratory
research purposes and which might even be applied as mupirocin substitute for eradication of
staphylococcal nasal colonization (Recsei et al. 1987, Kokai-Kun et al. 2003). Staphylococci are
resistant to lysozyme, a muramidase, which is present as antimicrobial enzyme in body fluids and
at sites of infection as part of the innate immune defense. The resistance is mediated by O-
acetylation in the muramic acid of peptidoglycan (position C6-OH) which is conducted by the
peptidoglycan-specific O-acetyltransferase OatA. OatA mutants are susceptible to lysozyme (Bera
et al. 2005).
The S. aureus genome has 32 % GC content. Its chromosome is about 2.7E+06 to 2.9E+06
nucleotides in length, contains about 2600 to 3000 genes, and has been sequenced for several
strains until now (Table I.1). Additionally, sequence information for several plasmids is available
(http://www.ncbi.nlm.nih.gov/sites/entrez?db=Genome).
For sub-division purposes, the S. aureus genome has been classified into two parts. The core
genome, which occupies approximately 75 % of the complete genome, includes genes with basic
functions e. g. in house-keeping and central metabolism. These genes are present in the genomes
of most strains and exhibit a high degree of conservation in the individual genes’ sequences in
different strains. The core part also features a high similarity to the phylogenetically related
Bacillus species genomes (Hiramatsu et al. 2004). The remaining 25 % belong to the accessory
part of the genome. This part consists of further genes which have been acquired by some
S. aureus strains e. g. from mobile genetic elements. Here, variation in the presence of genes is
observed in different strains. Many virulence genes are classified as fraction of the accessory
genome (Lindsay/Holden 2004).
S. aureus has many options of varying its accessory genome part by different mobile genetic
elements (Plata et al. 2009). Staphyloccoccal pathogenicity islands (SaPI) are located at constant
positions of the genome, contain superantigen genes and sequences with similarity to prophages
(Lindsay et al. 1998, Novick RP 2003). Similarly, genes of the νSa-family of pathogenicity genomic
islands, of which several types (1-4, α, β, γ) exist, code for virulence factors and toxins (Gill et al.
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