Discovery on New Insights in Bacterial Defence and Protection of the Peptidoglycan Wall
Scientists from Umeå University and Cornell University have discovered a newly formed bacterial defence mechanism arising from the regulation of activity of some enzymes via LD-crosslinking in the peptidoglycan cell wall. This mechanism increases bacterial resilience further and opens up new horizons for novel antibacterial therapies.
Like most living organisms, bacteria need defense mechanisms to survive. One such defense mechanism is the peptidoglycan or PG cell wall that protects the bacteria from any kind of invasion and withstands turgor pressure inside the cell. The space within the PG structure is generated through enzymes called autolysins while constructing this wall. Still, with these PG-degrading enzymes in mind, long hidden the regulatory mechanisms controlling these enzymes. This current research may open doors to new antibacterial treatment patterns in how bacterial infections are fought.
LD-Crosslinks: New Enzyme Activity Gatekeepers
A structural change in the PG wall, that was LD-crosslinking, has been involved in the regulation of the activity of such a type of autolysin, lytic transglycosylases (LTs), according to the research published in the journal Nature Communications. The enzymes break the glycan chains in the PG wall, which leads to the wall growing and remodeling. Nonetheless, experiments in the sacculus of the PG wall disclosed that such LD-cross-links play as negative regulators of the process of wall growth by limiting the proper amount of LTs’ activity.
This newly discovered regulation has deep biological implications. The limitation of LT activity is important as such in the protection of bacteria from extracellular attacks, such as viruses and predatory bacteria that have a lytic cycle dependent on LTs to break bacterial cell walls. It also guards against the uncontrolled release of immunogenic peptidoglycan fragments, which would have precipitated an immune response from the host. Therefore, in practice, LD-crosslinking is a gate, controlling the when and where LTs could break the PG wall.
Model for LD-crosslink mediated control of lytic transglycoslyase activity.
New Antibacterial Therapeutic Pathways
This is a very important finding,” said lead researcher Felipe Cava of Umeå University, who linked the gap to how bacteria maintain cell wall stability. What this research reveals in a nutshell is that antibacterial drug development could take a new direction by targeting LD-crosslinking. Scientists can inhibit this mechanism and therefore weaken the bacterial defenses, making bacteria more susceptible to existing treatments and immune responses.
Unlocking new avenues in antibacterial therapies
The discovery of LD-crosslinking as a mechanism of regulation in bacterial defense offers new, promising pathways for targeted antibacterial treatments. Laura Alvarez points out that disrupting regulation along such lines can make bacteria more vulnerable to natural immune responses and synthetic antibiotics, providing a promising strategy against strains of resistance. This discovery points to how structural alterations play a key role in bacterial survival. By targeting these mechanisms, we may soon start to see a new era of innovative therapeutic drugs bring hope to the ongoing fight against resistant bacteria.
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Other References:
Vollmer, W., Blanot, D. & de Pedro, M. A. Peptidoglycan structure and architecture. FEMS Microbiol Rev. 32, 149–167 (2008).
Cava, F. & de Pedro, M. A. Peptidoglycan plasticity in bacteria: emerging variability of the murein sacculus and their associated biological functions. Curr. Opin. Microbiol. 18, 46–53 (2014).
Egan, A. J. F., Errington, J. & Vollmer, W. Regulation of peptidoglycan synthesis and remodelling. Nat. Rev. Microbiol 18, 446–460 (2020).
Rohs, P. D. A. & Bernhardt, T. G. Growth and division of the peptidoglycan matrix. Annu. Rev. Microbiol. 75, 315–336 (2021).
