Can bacteria become resistant to phage?

The simple answer is yes!
Bacteria can resist phage attack through different mechanisms, including spontaneous mutations, restriction modification systems, adaptive immunity via the CRISPR-Cas system and/or programed cell death/abortive infection. Spontaneous mutations are the main mechanisms driving both phage resistance and phage–bacterial coevolution which may confer phage resistance by modifying the structure of bacterial surface components that act as phage receptors and that also determine phage specificity. These include lipopolysaccharides (LPS), outer membrane proteins, cell wall teichoic acids, capsules, and other bacterial appendices, such as flagella, many of which may all be part of virulence factors (e.g., LPS).
However, phage resistance may also induce trade-off costs. Phage-resistant bacteria may become less virulent in case of mutations in surface virulence factors, such as LPS. Likewise, the maintenance of anti-viral defence systems, such as for DNA restriction-modification enzymes and CRISPR-Cas adaptive immunity, also has its own cost. In some cases bacteriophages can cause the transfer of antibiotic resistance genes (ARGs) which is one of the undesirable feature to be brought by phage applications.
A bacteriophage ready to inject its DNA to a bacterium. photo by SciTechDaily

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