Question

Controlling microorganisms in the environment is becoming increasingly difficult due to the development of resistance to common disinfectants and antiseptics. Some examples of chemicals that have been or which are currently being used are triclosan, triclocarban, benzalkonium chloride, and chloroxylenol, to name a few. Many scientists are now turning their attention to other methods to control bacterial contamination. Discuss using 'phages' and other methods to control bacteria. Do you think these methods are better? Safer?

Answer 1

Bacteriophage are commonly referred to as phage and are defined as viruses that infect bacteria.

Phage are ubiquitous and require a bacterial host. The phage therapy is predominant because of the increase in multi-drug resistant (MDR) pathogens and the desire to find alternative treatment methods to the use of chemical antibiotics. The transmission electron microscopy shows that the phage have complicated structure. Two main features of tailed phage (order Caudovirales) include a capsid that encloses genetic material in the form of either DNA or RNA and a tail that varies in size among different bacteriophage.

Phage can undergo two different life cycles: the lytic cycle and the lysogenic cycle. Phage attach to the bacterial host specifically on a receptor found on the bacteria’s surface and injects its genetic material into the cell. The host cell provides the molecular building blocks and enzymes required to replicate the phage genetic material and produce progeny phage. Phage-encoded proteins such as endolysin and holin lyse the host cell from within. Holins are small proteins that accumulate in the cytoplasmic membrane of the host and allow endolysin to degrade peptidoglycan, allowing the progeny phage to escape. Subsequently, in the external environment, lytic phage can infect and destroy all neighboring bacteria. The production of large numbers of progeny by lytic phage is an advantage when lytic phage are used in phage therapy. However, lytic phage have narrow host ranges and infect specific bacterial species. This lack of a broad host range can potentially be overcome by using a phage cocktail. In the lysogenic cycle, temperate phage do not immediately lyse the host cell; instead, their genome is inserted into the host chromosome at specific sites. This phage DNA in the host genome is called a prophage, while the host cell containing the prophage is called a lysogen. The prophage is replicated along with the bacterial host genome, establishing a stable relationship. The disadvantage of using temperate phage in phage therapy is that some of the phage population insert their genome into the host chromosome and can lay dormant or alter the phenotype of the host. The lysogenic cycle can continue indefinitely unless the bacteria are exposed to stress or adverse environmental conditions. The induction signals vary among bacteriophage but prophage are commonly induced when bacterial SOS responses are activated due to antibiotic treatment, oxidative stress, or DNA damage. Once the lysogenic cycle is terminated, expression of phage DNA ensues and the lytic cycle starts.

The biological implication of this communication system is significant and explains that when a single phage encounters a large number or colony of bacteria, there are plenty of hosts to infect, favoring activation of the lytic cycle. As the host numbers become limited, it is more beneficial for the progeny phage to become dormant and enter lysogeny.

No, I do not think that the use of phage therapy better or safe because

1.      Intracellular pathogens have the advantage of surviving inside host cells, where they would presumably be inaccessible to phage due to the inability of phage to enter eukaryotic cell.

2.      Although phage are not direct pathogens of eukaryotic cells, the human immune system may recognize phage as foreign antigens and respond by producing phage-neutralizing antibodies.

3.      Administering high titers of phage to a patient may induce an extreme reaction such as anaphylaxis.

4.      The characteristic of phage that may be a disadvantage in phage therapy is their ability to pick up genetic material through horizontal gene transfer. The use of phage therapy could lead to the transfer of genes that increase the bacterial host’s virulence through general or specialized transduction mechanisms. Especially concerning is the possibility of transferring antibiotic-resistance genes and virulence factors.

5.      Another issue that arises with phage therapy is the possible downstream effects of lysing bacteria. When Gram-negative bacteria are lysed, the cellular components such as endotoxin may be released. This is a major problem associated with the use of certain antibiotics. If a large amount of endotoxin is released into the body, fever or septic shock can occur, which could lead to death. Therefore the use of phage therapy is not safe