Question

What is the relationship of temperate phages to the disease-producing ability of some bacteria? Why does this occur? What effect would treating the infection with antibiotics have? (detailed explanation please)

Answer 1

Temperate phage - In virology, temperate refers to the ability of some bacteriophages (notably coliphage λ) to display a lysogenic life cycle. Many (but not all) temperate phages can integrate their genomes into their host bacterium's chromosome, together with becoming a lysogen as the phage genome becomes a prophage

Infection caused by a temperate phage

The process in which a bacterium is infected by a temperate phage is called lysogeny. It is typical of temperate phages to be latent or inactive within the cell. As the bacterium replicates its chromosome, it also replicates the phage's DNA and passes it on to new daughter cells during reproduction.

Bacteriophages are viruses that infect bacteria. There are an estimated 10³¹ phage on the planet, making them the most abundant form of life

Temperate prophage carriage is often associated with increased bacterial virulence. The rise in the use of technologies, such as genome sequencing and transcriptomics, has highlighted more subtle ways in which prophages contribute to pathogenicity.

Bacteriophages (phage) are viruses that infect and replicate within bacterial hosts and are ubiquitous and abundant in every niche studied

They are broadly divided into two categories. Virulent phage follows a strictly productive lytic life cycle, whereas temperate phage switch between dormant and productive states. All phage infects the host bacterium by binding to specific surface receptors and injecting their genome into the cytoplasm. Virulent (lytic) phage infection immediately commandeers the bacterial replicative machinery for multiplication. Phage genes encode structural head and tail proteins and lytic enzymes that cause a bacterial cell to lyse, releasing lytic phage progeny into the environment. The characteristics of lytic phage offer an attractive alternative to antibiotics.

Temperate (lysogenic) phage follow an alternative life cycle involving the integration of their genome into the host chromosome to become a prophage. In this state, the phage DNA replicates along with the host cell (lysogen) and is maintained in the bacterial population. Lysogenic phage can switch to a lytic life cycle, particularly in response to environmental stresses

Lambdoid phage employ repressor genes such as cI, which act as a genetic switch to control the balance between lysis and lysogeny. The expression of these repressors prevents the lytic pathway and maintains the prophage state. The CI repressor also inhibits the integration of any incoming phage genomes conferring immunity to superinfection. There are a wide range of other phage resistance mechanisms

The balance between lytic and lysogenic states is thought to be largely dependent on the metabolic condition of the bacterial host cell. Temperate phage infection tends towards lysogeny in starving cells and this is thought to be a phage survival tactic during periods of resource limitation. Integration into the chromosome is facilitated by integrase and transposase enzymes that can act at specific sites or randomly. This means that lysogenic phage can drive bacterial diversity by introducing mutations with each integration event. Active prophage retains the ability to switch to a lytic cycle of productive replication. This occurs spontaneously in a proportion of cells within a population of lysogenic bacteria

PROPHAGE CONTRIBUTION TO INFECTION

Lysogenic infection and subsequent expression by the host of phage-encoded genes is termed lysogenic conversion and can have profound effects on bacterial phenotype. Prophages often encode ‘morons’ that are not directly involved in viral replication and can confer a benefit to their bacterial host. Such genes are independent transcriptional units of DNA that are expressed whilst the phage is in the prophage state Morons can include genes that enhance the virulence of their bacterial host, either directly (e.g. phage-encoded toxins) or indirectly, by enhancing the ecological fitness of bacteria during infection The role of temperate phage in disease situations is thus becoming increasingly recognized.

the recent growth in whole bacterial genome sequencing has revealed high numbers of integrated prophage Winstanley Pathogenic strains have been shown to carry a greater proportion of phage-related genes than non-pathogenic strains , many maintaining multiple prophages in the same chromosome For example, the majority of the genetic difference between avirulent and virulent strains of Escherichia coli is due to mobile genetic elements, notably phages

OCCURS - when the phage DNA integrates into the bacterial genome.

Answer-

Effects of antibiotic treatment

Long-term antibiotic treatment is likely to play a crucial role in the dynamics between prophage and their hosts in vivo. A longitudinal study of CF patient sputa tracked the density of six P. aeruginosa phage that is all maintained as active prophages in the same LES chromosome. A consistently high density of DNA from LES phage virions (10⁴–10^9° copies μl⁻¹) was observed that correlated positively with LES host numbers over a two-year period. Free-phage density exceeded specific bacterial host density (11–90-fold), consistent with ongoing lytic activity.

This was expected as CF patients are often treated with high doses of intravenous antibiotics during exacerbation of symptoms. Surprisingly, there was no correlation between LES phage density and treatment of exacerbated symptoms. These patients were subject to variable cocktails of different antibiotic classes over several years irrespective of exacerbations

Not all antibiotics induce the phage lytic cycle; in fact, some are known to suppress lytic activity. As next-generation sequencing technologies advance, the interaction between antibiotics, phage, and their hosts during chronic infections can be teased apart in further longitudinal studies.

Antibiotic resistance gene transfer between bacteria mediated by phages

It is well established that when bacteria acquire antibiotic resistance, new mutations can spontaneously occur or be achieved via horizontal transfer between cells of the same or different species. Phages are one of the vehicles of this genetic exchange. Antibiotic resistance genes (ARGs) in bacterial chromosomes or plasmids can be mobilized by phages during the infection cycle, a consequence of the inaccurate excision or encapsidation of the phage genome that allows for the incorporation of host genes by mistake. This mechanism, called transduction, was described in 1951 for many bacterial species and soon became a tool for molecular biology used to study bacterial genome