How to Kill Staphylococcus Aureus: A New Insight into Viruses That Can Defeat Bacteria

A team led by scientists from CEITEC Masaryk University has uncovered the infection mechanism of tailed bacteriophages – a group of viruses that infect bacteria. These phages target, among others, Staphylococcus aureus, a major cause of bacterial infections that is often resistant to antibiotics. The bacterium belongs to a group of Gram-positive bacteria characterised by an exceptionally thick cell wall. Although the infection mechanisms of some other bacteriophages have been described previously, the way tailed phages infecting Staphylococcus aureus and other thick-walled bacteria invade their hosts had remained unknown. The researchers have now revealed how such a bacteriophage breaches the protective barrier of the bacterial cell and delivers its genetic material inside. Their findings could contribute to the development of new strategies for combating antibiotic-resistant bacteria.

Staphylococcus aureus is one of the most common sources of bacterial infections in humans. It can cause skin infections, pneumonia, and even life-threatening bloodstream infections. Moreover, many of its strains have become resistant to commonly used antibiotics, increasing interest in alternative treatment approaches such as bacteriophage therapy.

“Bacteriophages are the most abundant biological entities on Earth and have been infecting bacteria for billions of years. Yet we still do not fully understand how they overcome the cell wall of certain Gram-positive bacteria. By reconstructing the bacteriophage structure before and after it attaches to a bacterial cell, we were able to reveal this process,” says Ján Bíňovský of CEITEC Masaryk University, who led the study together with Marta Šiborová.

Bacteriophage 812, investigated in this study, specifically infects Staphylococcus aureus. The researchers discovered that once it recognises the correct host, the protein structure at the tip of its tail undergoes extensive rearrangements. Individual components of this structure, which resembles a lunar landing module, reorganise into a new configuration that enables the virus to firmly attach to the bacterial surface. At the same time, a mechanism is activated that triggers contraction of the phage tail.

CEITEC/Plevka Lab: How to Kill Staphylococcus Aureus: A New Insight into Viruses That Can Defeat Bacteria: Phage before attachment to the bacterial cell.CEITEC/Plevka Lab: How to Kill Staphylococcus Aureus: A New Insight into Viruses That Can Defeat Bacteria: Phage attached to the bacterial cell.

“The process resembles the release of an extended spring. The bacteriophage tail contracts to approximately half of its original length, and the released energy drives the central tube through the bacterium's protective layers. The virus can then deliver its genetic material into the cell and initiate infection,” explains Marta Šiborová.

Unlike many other bacteria, Staphylococcus aureus possesses an exceptionally thick cell wall. The researchers therefore investigated in detail how the bacteriophage overcomes this barrier. They found that the virus employs a combination of mechanical force and enzymatic activity. Some components of its infection apparatus likely disrupt teichoic acids, which form the outer protective layer of the bacterial cell wall. Other proteins then degrade peptidoglycan, the main structural component of the cell wall. Finally, the bacteriophage penetrates the inner lipid membrane, allowing its central tube to enter the bacterial cell.

The findings show that the bacteriophage does not function as a simple "needle", but rather as a sophisticated nanomachine composed of dozens of cooperating proteins.

Although this is fundamental research, the findings may prove important for future medical applications. Bacteriophages are considered one of the promising alternatives for treating infections caused by antibiotic-resistant bacteria.

“If we want to use bacteriophages therapeutically in the future – or even engineer them for specific medical applications – we first need to understand in detail how they work. Our study provides fundamental insight into how bacteriophages recognise their hosts and initiate infection,” says Pavel Plevka, structural biologist and head of a research group at CEITEC Masaryk University.

The study, published in EMBO Journal, also involved researchers from the Faculty of Science, Masaryk University.

CEITEC/Plevka Lab: How to Kill Staphylococcus Aureus: A New Insight into Viruses That Can Defeat Bacteria: Black = protein structure at the tip of the tail after the conformational change; red = portion of the tail that has begun to contract; blue = portion of the tail that remains extended.

The original article

Conformational changes of the baseplate regulating tail contraction of Staphylococcus phage 812

Ján Bíňovský, Marta Šiborová, Maryna Zlatohurska, Jiří Nováček, Pavol Bárdy, Roman Baška, Karel Škubník, Tibor Botka, Martin Benešík, Roman Pantuček, Konstantinos Tripsianes & Pavel Plevka

EMBO J (2026)

https://doi.org/10.1038/s44318-026-00834-9 

licensed under CC-BY 4.0