Abstract

Staphylococcus aureus is a nosocomial bacterium causing different infectious diseases, ranging from skin and soft tissue infections to more serious and life-threatening infections such as septicaemia. S. aureus forms a complex structure of extracellular polymeric biofilm that provides a fully secured and functional environment for the formation of microcolonies, their sustenance and recolonization of sessile cells after its dispersal. Staphylococcus aureus biofilm protects the cells against hostile conditions, i.e., changes in temperature, limitations or deprivation of nutrients and dehydration, and, more importantly, protects the cells against antibacterial drugs. Drugs are increasingly becoming partially or fully inactive against S. aureus as they are either less penetrable or totally impenetrable due to the presence of biofilms surrounding the bacterial cells. Other factors, such as evasion of innate host immune system, genome plasticity and adaptability through gene evolution and exchange of genetic material, also contribute to the ineffectiveness of antibacterial drugs. This increasing tolerance to antibiotics has contributed to the emergence and rise of antimicrobial resistance (AMR), a serious problem that has resulted in increased morbidity and mortality of human and animal populations globally, in addition to causing huge financial losses to the global economy. The purpose of this review is to highlight different aspects of S. aureus biofilm formation and its overall architecture, individual biofilm constituents, clinical implications and role in pathogenesis and drug resistance. The review also discusses different techniques used in the qualitative and quantitative investigation of S. aureus biofilm and various strategies that can be employed to inhibit and eradicate S. aureus biofilm.

Highlights

  • Staphylococcus aureus is a Gram-positive pathogenic bacterium and is a major cause of different infectious illnesses in humans and animals [1,2]

  • Besides the extracellular polymeric matrix that shelters the Staphylococcus aureus cells are more resistant to antibiotics and exhibit differences in cell cells against antibiotics, the dormant and metabolically slow growing cells have been size and growth, gene expression and protein production, compared to their free living reported to add to antimicrobial resistance [28]

  • Microorganisms including S. aureus have the remarkable ability to enclose themselves in a protective environment, i.e., biofilms, to survive and cause recalcitrant infections

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Summary

Introduction

Staphylococcus aureus ( denoted as Staph. aureus or S. aureus) is a Gram-positive pathogenic bacterium and is a major cause of different infectious illnesses in humans and animals [1,2]. Similar to any other bacterial biofilm, a Staphylococcus aureus biofilm has two distinct components, i.e., water (about 97%) and the organic matter which includes EPS and microcolonies [5]. The EPS constitutes about 50 to 90% of the total organic matter of a biofilm and is a complex of different polymeric substances, such as extracellular DNA (eDNA), proteins and polysaccharides [6,7]. In Staphylococcus aureus biofilm, the major component of EPS is the polysaccharide intercellular adhesin (PIA) [8]. Staphylococcus aureus EPS contains a range of proteins including accumulation associated proteins (Aap), surface binding protein A (Spa), fibrinogen binding protein (FnBP) A and B, extracellular matrix binding protein (Embp), amyloid fibres and S. aureus surface binding protein (SasG) [10,11]. Despite of the presence of both positively and negatively charged species, the overall charge on the EPS surface is negative and can serve as a better target for positively charged moieties [17,18]

Biofilm Formation
Gene Expression and Quorum Sensing in Staphylococcus aureus
Gene Expression and Staphylococcus aureus Pathogenesis
Clinical Implications of Staphylococcus aureus Biofilms
Techniques and Strategies Used in Studying Staphylococcus aureus Biofilm
Direct Observation Techniques
Light Microscope and Transmission Electron Microscope
Profilometry and Scanning Electron Microscope
Fluorescent Tagging of Biofilm
Indirect Observational Techniques
Congo Red Agar Method
Detection of Biofilm Production by Microtiter Plate Assay
Biofilm-Associated Genes Detection by PCR
Mass Spectrometry
Strategies Used to Inhibit and Disrupt Staphylococcus aureus Biofilm
Antibiofilm Drugs and Functional Excipients
Other Antibiofilm Molecules
Conclusions and Future Perspectives
Findings
Methods
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