**3. General pathogenesis and clinical diseases**

### **3.1. Pathogenesis**

of virulence factors which help to establish infection by facilitating tissue attachment, tissue invasion and evading from host immune response. The ability to acquire resistance to multiple antibiotics classes makes *S. aureus*, a challenging pathogen to treat. Emergence and spread of *S. aureus* strains which are resistant to methicillin, referred to as methicillin-resistant *S. aureus* (MRSA) resulted in high morbidity, high mortality and increased treatment costs. Vancomycin remained gold standard drug to tackle these strains for years but the emergence of resistance restricted its clinical utility. Newer anti-MRSA antibiotics which were approved by U.S. FDA came as respite for clinicians. However, new antibiotic discovery efforts and non- antibiotic approaches to tackle MRSA should not be diminished considering the ability of the pathogen to acquire resistance to newer drugs quickly after their introduction in clinics. In this chapter, we present a comprehensive outlook of *S. aureus* with account on bacteriology,

*S. aureus* cells are Gram-positive and appear in spherical shape. They are often in clusters resembling bunch of grapes when observed under light microscope after Gram staining. The name 'Staphylococcus' was derived from Greek, meaning bunch of grapes (*staphyle*) and berry (*kokkos*) [1]. The scanning electron microscopic observation reveals roughly spherical shaped cells with smooth surface [2]. The diameter of the cells ranges from 0.5 to 1.0 μM [3]. The transmission electron microscopy of cells shows thick cells wall, distinctive cytoplasmic

*S. aureus* is an aerobic and facultative anaerobic organism that forms fairly large yellow or white colonies on nutrient rich agar media. The yellow colour of the colonies is imparted by carotenoids produced by the organism. The term 'aureus' is derived from Latin, which refers to the colour of gold [5]. The organism is often haemolytic in blood agar due to production of four types of haemolysins (alpha, beta, gamma and delta) [6, 7]. Nearly all isolates of *S. aureus* produce coagulase enzyme, a virulence factor that also helps in identification of the organism [6, 8]. The organism is salt tolerant, which is able to grow in mannitol-salt agar medium containing 7.5% sodium chloride [8]. The organism is catalase positive and oxidase negative.

The primary objective in laboratory diagnosis is to identify whether the diagnosed *S. aureus* isolate is methicillin resistant. Since MRSA emerged as problematic pathogen, a systematic diagnostic approach is necessary for early diagnosis so that treatment with appropriate antibiotics can be initiated as early as possible. For the species identification, slide and tube

pathogenesis, epidemiology, antibiotic resistance and therapeutic approaches.

**2. Bacteriology**

**2.1. Microscopic morphology**

membrane and amorphous cytoplasm [4].

**2.3. Medical laboratory diagnosis**

**2.2. General cultural and biochemical characteristics**

The process of *S. aureus* infections involves five stages. They are (1) colonization, (2) local infection, (3) systemic dissemination and/or sepsis, (4) metastatic infections and (5) toxinosis. The organism is in carrier state in the anterior nares and can remain so without causing infections for weeks or months. The colonization proceeds to infection under certain predisposing factors such as prolonged hospitalization, immune suppression, surgeries, use of invasive medical devices and chronic metabolic diseases. Localized skin abscess develop when the organism is inoculated into the skin from a site of carriage. This can further spread and results in various clinical manifestations of localized infections such as carbuncle, cellulitis, impetigo bullosa or wound infection. The organism can enter into blood and spread systemically to different organs causing sepsis. This haematogenous spread may result in endocarditis, osteomyelitis, renal carbuncle, septic arthritis and epidural abscess. Without a blood stream infection, specific syndromes can occur due to extra cellular toxins of *S. aureus*. These are toxic shock syndrome, scalded skin syndrome and foot borne gastroenteritis [9].

#### **3.2. Hospital and community infections**

*S. aureus* causes wide range of infections in human. The clinical infections of *S. aureus* are classified into community and nosocomial categories based on origin of infection. These two types are distinct in clinical manifestations of the infections, antibiotic susceptibility and the genetic background of the infecting *S. aureus* strains. For decades, *S. aureus* has been predominately a nosocomial pathogen and is a leading cause of mortality and morbidity in hospitals. However, the community *S. aureus* infections are in rise. The important clinical *S. aureus* infections are bacteraemia, infective endocarditis, skin and soft tissue infections, osteoarticular infections and pleuropulmonary infections. Other clinical infections are epidural abscess, meningitis, toxic shock syndrome and urinary tract infections [9, 10].

#### **3.3. Virulence factors**

*S. aureus* possess battery of virulence factors. These factors enable the organism to be successful as pathogen that causes wide range of human and animal infections. Virulence factors help in attachment to host cells, breaking down the host immune shield, tissue invasion, causing sepsis and elicit toxin-mediated syndromes. This is the basis for persistent staphylococcal infections without strong host immune response [11]. Based on their mechanism of action and role in pathogenesis, staphylococcal virulence factors are classified as represented in **Table 1** [9, 12].


**Table 1.** Virulence factors of *S. aureus* and its characteristics.
