Insights on Virulence and Antibiotic Resistance: A Review of the Accessory Genome of Staphylococcus aureus
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Staphylococcus aureus has been known as a causative agent of infection since 1882 when Alexander Ogston identified its role in sepsis and abscess formation.1 It has continued to be one of the most recognized human pathogens throughout the community and hospital settings. S aureus is an opportunistic bacterium, which is frequently part of the human microflora, causing disease when the immune system becomes compromised. Although S aureus can be found in different parts of the body, the anterior nares are the primary ecological niche in humans. Nasal carriage differs between individuals and is a significant risk factor for S aureus infection.2 In healthy populations, approximately 20% of individuals carry S aureus persistently, while close to 60% carry the infection intermittently, and about 20% do not carry it at all.2 From the nares, staphylococci may spread to the skin, surgical wounds, foreign bodies (eg, tracheostoma, external fixation devices), burns, and the upper respiratory tract. Moreover, about 80%–100% of patients with eczema and atopic dermatitis are known to be colonized with the organism—bacterial colonization is an important factor in aggravating skin lesions.3 Another mode of transient transmission is via colonized hands of healthcare workers who acquire the organism after close contact with colonized patients or contaminated equipment.4,5 S aureus can cause a wide range of infections that include 1) skin and soft tissue infections, such as bullous and nonbullous impetigo, folliculitis, cellulitis, surgical and wound infections, and mastitis; 2) systemic and life-threatening conditions, such as endocarditis, osteomyelitis, pneumonia, brain abscesses, meningitis, and bacteremia; 3) toxinoses, such as food poisoning, scalded skin syndrome, and toxic shock syndrome.6,7
There has been growing concern regarding the increasing level of antibiotic resistance in S aureus,especially the severeconsequences of hospital and community-acquired methicillin-resistant S aureus (MRSA).8–11 The advent of quinupristin-dalfopristin, (United States Food and Drug Administration [FDA]-approved in 1999), and antibiotics like linezolid (oxazolidinone, FDA approved in 2000) and daptomycin (lipopeptide, FDA approved in 2003) with their novel mechanisms of action against MRSA, offered some hope for the treatment of S aureus infection. However linezolid and daptomycin- resistant S aureus have been reported,12–15 reinforcing the need to control MRSA in the hospital and community settings. The menace of S aureus infections have therefore led to a great interest in sequencing the genome of this pathogen in order to provide detailed insight into how the organism generates a variety of virulence factors and develops resistance to so many antibiotics.16 It has also stimulated research in identifying targets on whose genes are essential for in-vivo and in-vitro growth,thereby exploiting antibiotic target identification and selection.17 To date, 8 complete genome sequencing of S aureus have been conducted (Table 1) and 7 have been published.18–21 The remaining sequenced strain is NCTC 8325.22 This review examines the accessory genome of sequenced S aureus strains and provides information on how this pathogen causes disease and exhibits resistance to a wide range of antibiotics.
Comparative Genomics of S aureus
References
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