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 programmed cell death/abortive infection. Random 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 determine phage specificity. These include lipopolysaccharides (LPS), outer membrane proteins, cell wall teichoic acids, capsules, and other bacterial appendices, such as flagella, 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 defense systems, such as DNA restriction-modification enzymes and CRISPR-Cas adaptive immunity, also costs. In some cases, bacteriophages can cause the transfer of antibiotic resistance genes (ARGs), which is one of the undesirable features to be brought by phage applications.
A bacteriophage is ready to inject its DNA into a bacterium. photo by SciTechDaily

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