A Short Review on Advances in Nanosystems Emerging as an Effective Approaches to Control Pathogenesis of Staphylococcus spp

The Staphylococcus is a gram positive facultative aerobic bacteria. It belongs to the family Staphylococcaceae and order Bacillales. It mainly reside on the skin and mucous membrane of humans and other animal. Staphylococcus is an opportunistic pathogen mainly colonize on human anterior nares and causes life threatening bloodstream infection like sepsis and endocarditis. It causes hospital-acquired infections mainly in soft tissue by confi scating the host defense and coagulation systems [1]. The infections creates high mortality rate despite of the proper treatment. Staphylococcus aureus is one of the most fatal bacteria, approx 20% to 50% mortality has estimated [2]. It causes infl ammation and immunosuppression which leads to Abstract


Introduction
The It causes infl ammation and immunosuppression which leads to the disseminated intravascular coagulation (DIC), damage the endothelium layer and blocks blood stream as well as resulted as oxygen depletion in organs [3,4]. The adhesion process is the key step for the pathogenesis of S. aureus by secreting many toxins. They also secrete many factors like fi bronectin binding protein A (Fnbp A), Fnbp B and teichoic acid which promote colonization at infection site and resist to immune response of the host [5]. The S. aureus develops resistance to -lactams, daptomycin and glycopeptide antibiotics. Moreover, Methicillin-Resistant Staphylococcus aureus (MRSA) also develops an antibiotic resistance by over secreation of lactamases and reducing the effi cacy of antibiotics.
Due to ingenious survival strategies many antibiotics are ineffective in the treatment of S. aureus. Therefore, deal with Citation: Giri [7,8].
This review describe the pathogenesis mechanisms of Staphylococcus such as immune clearance, membrane permeability and production of -lactamase. We have compiled the several nanosystems which are previously known as a bactericidal agent for Staphylococcus spp. and their action mechanism also be summarized herein.

Pathogenesis mechanisms of Staphylococcus which causes infection
By immune clearance: In the bloodstream, Kupffer cells effi ciently regulates Staphylococcus survivability by phagocytosis while sometimes the phagocytosis process has compromises then staphylococci certainly survive and multiply inside the cells. Thus, they release from intracellular niche and encounters by the peritoneal macrophages and bloodstream neutrophils [9]. An essential attributes of Staphylococcus requires to create infection and coordinate with timely expression of virulence factors along with relevant genes.
Several reports are highlighted the genetic adaptation system 'accessory gene regulator' (Agr) or quorum-sensing system in S. aureus which requires for secretion of number of toxins and other soluble virulence factors [10]. It senses an auto inducing peptide (AIP) secreted by the S. aureus itself. The activation of Agr signaling occurs when AIP reaches a critical concentration due to high bacterial density. An active Agr system is essential for intracellular survival of S. aureus or inside the phagocytes cells [11].
By membrane permeability: The cell membrane permeability is another factor which directly relates to the bacterial survivability. Drug absorption is reduces when the energy metabolism of the bacteria is affected and creates a lower cell membrane permeability and leads to the drug resistance [12].
Long term exposure of drugs activates the effl ux system which enhance the effl ux of drugs and develop a drug resistance in the bacteria [13]. The effl ux proteins exchanges takes place by electrochemical gradient formed by H + on both side of cell membrane [14]. Majorly, three multidrug-pumping proteins viz; QacA, NorA, and Smr present on the Staphylococcus aureus cell membrane (Foster, 2016). Among these, QacA is an important factor in MRSA [15].
By production of beta lactamase: The -lactamase causes hydrolysis of -lactam antibiotics and develops a lethal effect on bacteria by two mechanism (i) by binding to the penicillin binding protein which repress mucin synthesis in cell wall and leads to the cell wall disruption as well as bacterial lysis (ii) by trigger autolytic enzyme activity of bacteria [16].
Moreover, MRSA also develops an antibiotic resistance by over secreation of lactamases. It reduces the effect of antibiotics by hydrolysis of -lactamase and resulted as inactivation of antibiotics. -lactamase binds to the antibiotics and prevents them to reach the target site .

Action mechanism of nanomaterials to prevention of Staphylococcus spp. infection
Nano pharmaceuticals could effi ciently administer to the human body by orally, intravenously, respiratory system and topically [17]. The size, shape, surface charge, chemical composition and hydrophobicity of nanosystems infl uences to the intestinal mucus. The mechanism of action is different with different set of nanomaterials for example liposome nanomaterials with PEG coating are easily able to penetrate in mucus layer than nanomaterials coated with chitosan. The negative charges presents on the surface of nanomaterial as well as mucus that causes repulsion and hydrophilicity of the mucus surface [18]. A previous study suggested that zinc

Metal nanoparticles
The metal nanoparticles exhibits potential antibacterial activity and helps to overcome resistance in pathogens. Their mechanism of action involves in metal ion release, cell wall and membrane disintegration, ROS generation, intracellular penetration and DNA damages [20]. Silver nanoparticles are widely accepted for their effective antibacterial activity by altering the cell wall protein, inhibits cell division, disrupt signal transduction and cause ROS production [21]. Recently our research team also reported the strong bactericidal activity of Citation: Giri Table   1.

Advantages and disadvantages of nanosystems
Increase in antibiotic resistance in bacteria emerges as a greatest challenge to human health. Though, deal with nanomedicine plays a vital role in increasing the potency of existing therapies, by increasing stability and physiochemical Li ,et al. [37] Figure 1: A comparative study of biogenic silver nanoparticles (BSNP) and chemical counterparts (CSNP) against S. aureus. Image adopted from Kumari, et al. [22].
properties of antibiotics, by biofi lm internalization, prolongation of antibiotic release and targeted delivery of drug to the site of infection [58]. Size and surface potential of nanomaterials drives interaction with various component of the tissue and regulates intracellular uptake and biodistribution [59]. Hydrophobic property of nanomaterials helps in targeting the drugs to the targeted site and enhance the adhesion effi cacy [58]. Nano-sized systems have ability to impede the instigation of resistance as well as vanquishing the resistance strategies of bacteria [60].
Several lipids sensitivity occurs due to high temperatures as well as fabrication techniques are very complex, expensive, and diffi cult to be scaled up [63].