Outcomes of Phage Infections

The infectious process arisen in bacterial cells by specific bacteriophages can be resolved in various ways.

Virulent phage infection leads to the burst maturation of new phages with further lysis of the bacterial cell. In this case the cycle of phage propagation lasts for 30-90 minutes. It is the variant of productive viral infection that is followed by host cell disruption with massive virion egress.

Lysogenic infection or lysogeny is caused by temperate phages. These phages can integrate its DNA into the nucleoid of bacterial cell. Phage DNA then replicates as an integral part of the bacterial chromosome.

Nucleoid-integrated bacteriophage is known as a prophage, while the bacterial cell infected with prophage is called a lysogenic cell, or lysogen.

The well-known example of temperate bacteriophage is the phage lambda, which interacts with E. coli.

Phage DNA integration into the bacterial chromosome is possible due to site-specific recombination between bacterial and phage genomes. Short nucleotide sequences in the DNA of phage and host nucleoid are homologous, allowing closest phage and bacterial DNA interaction (synapse) with subsequent genomes consolidation (for details see the Chapter of bacterial genetics).

Being integrated, the phage DNA can remain in the prophage state for a long period of time. Its expression can enrich the host cell with some new properties. This bacterial cell state is known as lysogenic (or phage) conversion. Very often conversed bacterial cells become virulent after phage acquisition. For instance, Corynebacterium diphtheriae, Clostridium botulinum and Vibrio cholerae start to express extremely poisonous exotoxins. That is true also for beta-hemolytic streptococci, which acquire the ability to produce erythrogenic toxin that actively participate in scarlet fever, and for salmonellae that change LPS structure of cell wall due to phage infection.

From the other hand, if prophage disappears from bacterial cell, the cell becomes avirulent.

In the period of lysogeny the infected cell acquires the immunity to a certain type of phage. Repressor protein, encoded by one of integrated viral genes, blocks possible transformation of prophage into active virulent form.

Bacteriophage activation with excision of viral genome (phage induction) is usually an accidental low-incidence process. It is occurred after lysogenic bacterium exposure to ultraviolet light, irradiation, chemicals action, etc. In that case the prophage transforms into a mature vegetative phage.

Sometimes after non-proper excision temperate bacteriophages can capture the bacterial genes surrounding phage nucleic sequence. In that case the phage becomes defective but able to transfer different host bacterial genes to other susceptible bacteria.

This phenomenon is known as transduction, and it makes available the exchange of genetic material between bacterial cells. This results in great raise of bacterial population diversity, which is valuable for microbial evolution. Molecular transduction is actively used in genetic engineering.

Filamentous phages can leave the infected cells without their destruction. All of them are of single-stranded DNA genome. Filamentous phages release is known as extrusion from the bacterial cell. In that case infected bacteria save their ability to cell division. Infected bacteria are called as carrier cells.

Finally, about 50% of bacterial species are proven to carry special genetic region responsible for so-called bacterial “adaptive immune system”. This system maintains the specific protection of microbial cells against bacteriophage infection. For instance, it is essential for many aggressive human pathogens like M. tuberculosis or Y. pestis.

Genome of these bacteria contains the number of genetic elements known as CRISPR cassettes (abbreviation “CRISPR” means “clustered regularly interspaced short palindromic repeats”).

CRISPR cassette includes many short genetic spacers of similar length but of different DNA sequence interspersed between almost identical direct repeats of DNA. A single CRISPR cassette may contain more than 100 spacers. Every spacer harbors a short sequence of foreign DNA captured by bacterial cell during the previous infection with bacteriophage or plasmid.

The genetic elements of this system control the acquired defensive reactions of bacterial cell against the invaded foreign nucleic acid of bacteriophage. Furthermore, the genetic information of invaded DNA is memorized in bacterial genome and becomes heritable. As the result, next entry of the same nucleic acid of bacteriophage leads to the activation of specific RNA-mediated enzymatic reactions that actively eliminate the extraneous nucleic acid of phage.

The family of bacterial enzymes with integrase and nuclease activity generally termed as Cas proteins are responsible for uptake and degradation of phage nucleic acids. They are encoded by special bacterial genetic locus cas (cas means CRISPR-associated) that borders with CRISPR genetic region.