Virulence factors carried on Phage


Temperate phage can go through one of two life cycles upon entering a host cell. Lytic growth results in lysis of the host and release of progeny phage. Alternatively, lysogenic growth results in integration of the phage DNA into the host chromosome or stable replication as a plasmid. Most of the gene products of the lysogenic phage remains dormant until it is induced to enter the lytic cycle. However, many lysogenic phage express gene products that hav subtle effects on the phenotype of the host cell. This process is called lysogenic conversion.

Some lysogenic phage carry genes that can enhance the virulence of the bacterial host. For example, some phage carry genes that encode toxins. These genes, once integrated into the bacterial chromosome, can cause the once harmless bacteria to release potent toxins that can cause disease. Some examples of virulence factors carried by phage are shown in the table below.

BacteriumPhageGene ProductPhenotype
Vibrio choleraeCTX phagecholerae toxincholera
Escherichia colilambda phageshigalike toxinhemorrhagic diarrhea
Clostridium botulinumclostridial phagesbotulinum toxinbotulism (food poisoning)
Corynebacterium diphtheriaecorynephage betadiphtheria toxindiphtheria
Streptococcus pyogenesT12erythrogenic toxinsscarlet fever

The effect of lysogenic conversion can be seen clearly in the disease cholera. Cholera is caused by a Gram negative, curved rod called Vibrio cholerae. The bacterium is transmitted through contaminated water and results in severe diarrhea and rapid dehydration of the infected person. The most effective treatment involves intravenous or oral liquid replacement therapy. V. cholerae did not always cause disease. Infection with the CTX phage gives the bacterium its toxinogenicity. The phage recognizes a pilus on the surface of the bacterium and uses it to enter the cell. Once inside the cell, the CTX phage integrates into the chromosome and the lysogen expresses cholera toxin.

The CTX phage has received special attention because it is the first filamentous phage found to transfer toxin genes to its host. The important lesson from this discovery is that many different types of phage may carry virulence factors, and transfer of virulence genes by phage may be a major mechanism of evolution of new bacterial diseases.

In addition, the ability to transfer virulence genes by phage has important implications on the development of vaccines against bacteria. For example, some of the first vaccines tested against V. cholera had a chromosomal deletion of the gene encoding cholera toxin. This resulted in a bacterium that was nonvirulent, and thus was useful for human vaccines. However, the vaccine strain could readily acquire a functional copy of the cholera toxin gene by infection with CTX phage, turning an innocent vaccine strain into a fully virulent strain.

References


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This page was prepared by Kim Nicol.
Please send comments, suggestions, or questions to smaloy@sciences.sdsu.edu
Last modified November 26, 2003