It depends on the host and the genetic tools developed for that host. It also depends if the prophage is integrated in the genome or not.

For chromosomal prophages in genetically manipulable species, you can simply rely on general recombination, i.e. give it a PCR product that contains sufficient homology on each side of the prophage you want to delete. You can also put an antibiotic cassette in your PCR product (in between homology regions - basically you'll be replacing the prophage with antibiotic cassette). That'll simplify the screening. If you want a scarless, clean deletion, you'll have to do more screening. You can also first insert an antibiotic cassette in the prophage, and then screen for loss of resistance.

For phages that are episomal, i.e. exist as free linear or circular DNA fragments, you can attempt to target the prophage with a CRISPR/Cas9 system. Perhaps you could also use acridine orange or EtBr to cure an episomal prophage (plasmids have been cured this way), but I suspect you'll introduce off target mutations in the bacterial genome.

Keep in mind that phages can bear addiction modules (toxin / anti-toxin systems) and they are not always easily identifiable. This would presumably complicate the curing unless you first inactivate the toxin component, or overexpress the antitoxin from a plasmid.

Good luck

Hey Panos,

As Ognjen Sekulovic already suggested you can learn about diparental and triparental mating if you want to delete chromosomal genes from a bacterial. It is difficult to delete all the prophage genes at once even if they are next to each other, maybe target most important and well annotated ones at first and then continue to the least ones. Repeated application of CRISPR/Cas system can also help but you should expect off target mutations as well.

Take care

You can not know how many copies of prophage that your bacteria has :)).

I assume you have just have one type of sequencing data and with respect to their low GC repeated zones can not be fully assambled so that you may not know exact repeat number and hard to CRISPR/Cas (copies tend to variation and its problematic job to find out all variants. But if you are luck no variant and less copy CRISPR/Cas might be a solution.

Lets say you are an entomologist and focused on a wolbachia having prophage and try to cure prophage from bacteria that you do not know how many copies of prophage or how many variants in the mutant clouds. Generally the simple way to cure viruses from the host trying to activate self to non-self perception by alternating temperatures of hosts. (Remember sometimes alternating temperatures might be lethal for the hosts in some of the viral infection cases.)

Histone methylases, dicers and H-Ns might be elevated by the temperature cycles and might provide non-spesific viral silencing.