INSILICO IDENTIFICATION 0F PUTATIVE DRUG TARGETS IN STAPHYLOCOCCUS AUREUS
Introduction
As a member of the staphylococcaceae family, Staphylococcus aureus is regarded as an opportunistic pathogen for several mammals, including livestock and humans (Lowy1998, projan and novick, 1995). According to reports, Staphylococcus aureus is resistant to several of the antibiotics available on the market (Lowy, 1998; walsh and bowe, 2002). This bacterial strain is well known for producing a number of serious and fatal diseases, including meningitis, scalded skin syndrome, toxic shock syndrome, osteomyelitis, bacteremia, endocarditis, and food poisoning ( Lowy, 1998; drekema et al ., 2001 ). It is the main cause of pneumonia, lower respiratory tract infections, surgical site infections, cardiovascular infections, and the second greatest cause of nosocomial bacteremia (Richard et al., 1993). (Richard et al., 1993).In addition to these illnesses, it is also present on human skin and causes serious issues such acne, sour throat, hair follicle infections, pimples, and sties (a sty is an inflammation of a gland in the eyelid). Boils are deeper, pus-filled abscesses of the skin and underlying tissue that are also caused by it (freeman-cook and freeman-cook, 2006 Carleton et al., 2004; king et al., 2006). Staphylococcus aureus, like other facultative aerobes, can develop in the absence of oxygen by fermenting or by utilising a different terminal electron acceptor, like nitrate.Numerous studies indicate that oxygen contributes to the pathogenesis of staphylococcus aureus, both in terms of the bacteria’s ability to create virulence factors and to survive and thrive in a variety of frequently unfavorable environmental niches (Chan and foster, in 1998; clement and foster, ohisen et al., 1997; Ross and onderdonk, 2000). A number of virulence factors, such as adhesion, colonization, exoenzymes and exotoxins, capsule, etc., are present in or produced by the bacterium. By binding to proteins like fibronectin, laminin, vitronectin, and collagen that make up the extracellular matrix of epithelia and endothelia surfaces, these virulence factors enable bacteria to attack host cells (Gillaspy et al., 1990; freeman-cook, 2006).
About 90% of staphylococcus aureus strains are currently resistant to penicillin and its derivatives. Antibiotic resistance among staphylococcus aureus strains originated and spread quickly. New variants of penicillin were introduced to address this issue (Lowry, 2003; freeman-cook, 2006).
Approximately 50% of staphylococcus infections are now resistant to multiple drugs (resistant to penicillin, methicillin, tetracycline, and erythromycin). For many years, one antibiotic was known for its ability to prevent the emergence of resistance microorganisms. The name already indicates how it has been used, and it is frequently considered a “last resort.” So, the conflict between humans and microorganisms goes on (Freeman- cook et al., 2006)In other pathogenic species including Helicobacter pylori and pseudomonas aeruginosa (Sakharkar et al., 2004; Perumal et al., 2007), the computational approach has been used to investigate novel therapeutic targets (outla et al., 2006). Antibacterials are essentially enzyme inhibitors, as is now understood. In this study, we used a comparative pathway analysis technique to identify possible targets for inhibiting Staphylococcus aureus. Only enzymes that exhibit distinct characteristics from the host were chosen as the target.The pioneer of both nosocomial and community-acquired infections is Staphylococcus aureus. According to Richard et al. (1993), it is the main cause of lower respiratory tract infections and surgical infections. It is also the second greatest cause of pneumonia and cardiovascular infections (Richards et al., 1999). Staphylococcus aureus infections are particularly difficult to treat because of evolved resistance to antimicrobial drugs like penicillin newer narrow-spectrum -lactamase-resistant penicillin antimicrobial drugs (such as methicillin, oxacillin) and this resistance appeared shortly after they were introduced into clinical practice, respectively in the 1940s and 1960s (Lowy et al., 2003 ).Penicillin resistance was first limited to a small number of hospitalized patients, but as penicillin use rose, resistance first spread to other hospitals and subsequently to the general public (chambers at el., 2001). By the late 1960s, more than 80% of staphylococcus aureus isolates from hospitals and the general public were penicillin-resistant (Lowy et al., 2003). According to a recent analysis, methicillin-resistant staphylococcus aureus (MRSA) appears to be spreading and evolving in a wavelike fashion (Chamber et al., 2001). MRSA is currently endemic and epidemic in many US hospitals, along with long-term care homes, and communities (Straus Baugh et al., 1960).According to statistics from the National Nosocomial Infections Surveillance System, the percentage of methicillin-resistant Staphylococcus aureus isolates in intensive care units has climbed to 59.5%–64.4%. (klevens et al ., 2006). To comprehend the scope of the issue, accurate incidence estimates at the national level are required. However, national studies that look at the impact of MRSA or staphylococcus aureus on the healthcare system are older than five years (Kuehnert et al., 2005). According to Noskin et al., 125, 969 (43.2%) of the 290,000 hospitalizations for staphylococcus aureus in 1999–2000 were likely due to methicillin resistance (Kuehnert et al., 2005).This virus can cause a variety of diseases, from minor ones like skin infections and poisoning to serious ones like pneumonia, sepsis, osteomyelitis, and endocarditic infections. Methicillin-resistant staphylococcus aureus, which was initially identified in 1961 and currently has a mortality rate of 39% compared to MRSA’s 24% [laupland et al., 2008], is regarded as a superbug
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