2 Introduction
1997; Patel et al., 1987; Peacock et al., 1999).
2.2 Antibiotic resistance of S. aureus
To date antibiotics are the only effective therapy against S. aureus infections. However, the
steadily increasing incidence of S. aureus strains, resistant to multiple antibiotics aggra-
vates the treatment, thereby leading to increased mortality by S. aureus infections.
Today MRSA is the common denotation for those multiple resistant S. aureus, although
it was initially used for ’Methicillin resistant S. aureus’ conferred by an additional penicillin
binding protein (PBP2a). The mecA gene encoding PBP2a is located on a DNA element
termed SCCmec (staphylococcal cassette chromosome mec), site-specifically integrated
into the staphylococccal genome (Beck et al., 1986; Berger-Bachi et al., 1986).
For the treatment of infections caused by MRSA the glycopeptide antibiotic Vancomycin
still represents the antibiotic of choice. However, due to the selective pressure during treat-
ment, Vancomycin intermediate resistant S. aureus (VISA) evolved, first described in 1997
by Hiramatsu et al. (1997). In contrast to other antibiotic resistances this intermediate resis-
tance against Vancomycin is not genetically encoded. In 2002 the first case of a genetically
determined Vancomycin resistance (VRSA) was reported (Weigel et al., 2003). In this case
the vanA gene, conferring resistance to Vancomycin, was horizontally transferred from a
Vancomycin resistant Enterococcus faecalis during co-infection.
Until the late 1990s the predominant pattern of MRSA infections in the USA remained
a nosocomially acquired disease, but then MRSA from community-acquired sources (CA-
MRSA) without a history of intravenous drug use began to be described more frequently
(Corriere and Decker, 2008). In 2006 the overall prevalence of CA-MRSA in the population
was 59 %. Due to an almost three times longer stay for inpatients suffering from S. aureus
infection causing nearly thrice the cost compared to non-infected inpatients, infections with
MRSA also became an economic problem. Moreover, the treatment of infections caused by
MRSA, which accounts for almost 50 % of S. aureus related infections in several US hos-
pitals, even doubles the cost caused by infections with a methicillin susceptible S. aureus
(MSSA). The mortality rate associated with MRSA infections is with 20.7 % almost thrice
as high than observed for infections caused by susceptible S. aureus (6.7 %) (Corriere and
Decker, 2008). Next to this also the prevalence of CA-MRSA is steadily increasing. In
the United States a single clone of CA-MRSA (USA-300) has become the most prevalent
cause of staphylococcal soft tissue infections acquired in the community (King et al., 2006;
Tenover et al., 2006) and has entered the inpatient setting, causing also invasive diseases
(Davis et al., 2006; Gonzalez et al., 2006; Klevens et al., 2007).
The drastic increase in both nosocomially and community acquired MRSA related in-
fections and thereby increased mortality rates highlight the pressing need for alternative
strategies to prevent and treat S. aureus infections.
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