Staphylococcus aureus epidemiology, pathophysiology, clinical manifestations and application of nano-therapeutics as a promising approach to combat methicillin resistant Staphylococcus aureus

Abstract

Staphylococcus aureus is a Gram-positive bacterium and one of the most prevalent infectious disease-related causes of morbidity and mortality in adults. This pathogen can trigger a broad spectrum of diseases, from sepsis and pneumonia to severe skin infections that can be fatal. In this review, we will provide an overview of S. aureus and discuss the extensive literature on epidemiology, transmission, genetic diversity, evolution and antibiotic resistance strains, particularly methicillin resistant S. aureus (MRSA). While many different virulence factors that S. aureus produces have been investigated as therapeutic targets, this review examines recent nanotechnology approaches, which employ materials with atomic or molecular dimensions and are being used to diagnose, treat, or eliminate the activity of S. aureus. Finally, having a deeper understanding and clearer grasp of the roles and contributions of S. aureus determinants, antibiotic resistance, and nanotechnology will aid us in developing anti-virulence strategies to combat the growing scarcity of effective antibiotics against S. aureus.

Keywords: MDR; Staphylococcus aureus; antibiotic resistance; mesoporous silica nanoparticles; nanotechnology.

Figure 1.

Staphylococcal scalded skin syndrome. superficial blistering on the face (left) and in the axilla (right). Original image provided by Kiran Motaparthi, MD [51]‎.

Figure 2.

S. aureus mechanisms to initiate systematic infections. When S. aureus penetrates ‎the skin’s natural defenses or spread through a biofilm that might develop on indwelling ‎medical equipment, systemic infection is commonly the result. By actively attacking and ‎killing immune cells like neutrophils in the circulation with cytolytic toxins, the bacteria can ‎also remain in these cells and spread throughout the body, the bacteria can also spread through ‎the bloodstream and invade more cells. Many bacterial factors, including particular surface ‎proteins, toxins, exoenzymes and other compounds, can affect the development of an abscess ‎later on [1]. ‎.

Figure 3.

Distribution of VRSA, VISA and hVISA isolates among different countries based on meta-analysis of published original articles [113].

Figure 4.

MRSA antibiotic resistance mechanism S. aureus has methicillin resistance. Nasal and skin colonization are influenced by the expression of the surface protein adhesins and the wall teichoic acid. Insertion of the SCCmec horizontally transmitted DNA element results in methicillin resistance. Site-specific recombination allows for the integration of five separate SCCmec components at the same site. The mecA gene encodes PBP2a, a new β-lactam-insensitive penicillin binding protein [119].

Figure 5.

Multifunctionalities of MSNs. MSNs have multiple uses in the treatment of bacterial infections. On the top surface, agents that target bacteria and/or biofilm can be grafted. Adsorbed or grafted antimicrobial medications and/or antibiofilm substances are both possible for MSNs. To stop cargo leakage, stimuli-responsive gatekeepers can be included into blocking nanocaps. Pore uncapping and cargo release are triggered by exposure to internal (bacteria, pH, redox potential) or external (heat, light, alternating magnetic fields (AMF)) stimuli. MSNs can have antimicrobial metal NPs (M) and ions (Mn+) implanted within the mesoporous structure or coated externally. To add “stealth” qualities, biocompatible hydrophilic polymers can be grafted to the surface. To alter surface charge, different organic groups (R) can be externally functionalized. It is also possible to integrate fluorescent compounds and magnetic NPs [192].