Phage and Staphylococcus aureus

The emergence of methicillin-resistant Staphylococcus aureus and vancomycin-resistant S. aureus has made phages widely recognized as effective alternatives or supplements to antibiotics. With comprehensive knowledge about phage and Staphylococcus aureus, Creative Biolabs offers support for the development of therapeutic phage against Staphylococcus aureus.

Staphylococcus aureus

S. aureus is a Gram-positive bacterium that is one of the common flora on mammalian skin and mucous membranes. About 20-25% of people are persistent carriers of S. aureus. It is primarily found in the anterior nasal hall, while the oropharynx, armpits, perineal mucosa, skin, gastrointestinal tract, and vagina are also common sites of infection. Infection with S. aureus is a common cause of bone, joint, skin, and soft tissue infections, and also causes life-threatening diseases such as bacteremia, sepsis, infective endocarditis, etc. As a common hospital-acquired pathogen, S. aureus also causes device-related infections and seriously threatens the healthcare system.

Fig.1 SEM image of Staphylococcus aureus. (Archer, 2011)

Drug Resistance of Staphylococcus aureus

The spread and colonization of vancomycin-resistant and methicillin-resistant S. aureus further narrow the treatment options for staphylococcal infections, which can easily transition from acute to persistent, chronic, or recurrent infection. In 2017 the World Health Organization listed S. aureus as one of the most threatening drug-resistant pathogens with an urgent need for new treatments. S. aureus strains commonly used for phage propagation and culture include TX1330, KCOM 1162, RN4220, and CC30.

Phage and Staphylococcus aureus

Various trials have shown that phages can be used as an alternative or supplement to antibiotics to treat infections caused by antibiotic-resistant S. aureus. Morphologically, all currently known S. aureus-infecting phages belong to Cauroviridae, including Podoviridae (44AHJD, GRCS, P68, etc.), Myoviridae (phage K, SA5, GH15, etc.), and Siphoviridae (3MRA, 187, phiSauS-IPLA88, etc.).

Fig.2 Life cycle assay of phage SA1. (Zhang, 2022)

Phage-Staphylococcus aureus Interaction

S. aureus produces multilayered biofilms and expresses heterogeneous proteins. The solid components of biofilms are mainly composed of teichoic acid, Staphylococcus, host proteins, and polysaccharide antigens. Biofilm components tend to protrude from the cell surface, making them easily identified and captured. Common recognition molecules of S. aureus phage include wall teichoic acids (WTAs), lipoteichoic acids (LTAs), polysaccharides, or protein antigens. Phages often adopt a dual strategy for host adhesion. They deploy adhesion modules on the capsid and tail to recognize specific structures in a reversible manner, and then irreversibly bind to specific receptors after recognition. After the phage attaches to the host cell, enzymes on the tail spikes cleave the bacterial cell wall and reach the cytoplasmic membrane, ejecting the phage DNA into the bacterial cytoplasm.

Fig.3 The mechanism of bacteriophages inject genetic information into S. aureus cell. (Hrebik, 2019)

Phages of S. aureus have been isolated worldwide, but phages with therapeutic and application potential still require comprehensive evaluation before practical application. To help address the enormous threat of S. aureus, Creative Biolabs offers academic knowledge and strong support for the development of phage-based therapies against Staphylococcus aureus. Please do not hesitate to contact us for more information.

References:

1. Archer, N.K.; et al. Staphylococcus aureus biofilms: Properties, regulation, and roles in human disease. Virulence. 2011, 2(5): 445-459.
2. Zhang, B.Y.; et al. Interactions between jumbo phage SA1 and Staphylococcus: a global transcriptomic analysis. Microorganisms. 2022, 10: 1590.
3. Hrebik, D.; et al. Structure and genome ejection mechanism of Staphylococcus aureus phage P68. Science Advances. 2019, 5: 7414.