The CTXφ bacteriophage is a

filamentous bacteriophage Filamentous bacteriophage is a family of viruses (''Inoviridae'') that infect bacteria. The phages are named for their filamentous shape, a worm-like chain (long, thin and flexible, reminiscent of a length of cooked spaghetti), about 6 nm ...

. It is a

positive Positive is a property of positivity and may refer to: Mathematics and science * Positive formula, a logical formula not containing negation * Positive number, a number that is greater than 0 * Plus sign, the sign "+" used to indicate a posi ...

-strand

DNA virus A DNA virus is a virus that has a genome made of deoxyribonucleic acid (DNA) that is replicated by a DNA polymerase. They can be divided between those that have two strands of DNA in their genome, called double-stranded DNA (dsDNA) viruses, and ...

with single-stranded DNA (ssDNA). CTXφ infects some strains of ''

Vibrio cholerae ''Vibrio cholerae'' is a species of Gram-negative, facultative anaerobe and comma-shaped bacteria. The bacteria naturally live in brackish or saltwater where they attach themselves easily to the chitin-containing shells of crabs, shrimps, and oth ...

'', the

bacterium Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were amon ...

that causes cholera. It carries the genes for

cholera toxin Cholera toxin (also known as choleragen and sometimes abbreviated to CTX, Ctx or CT) is AB5 multimeric protein complex secreted by the bacterium ''Vibrio cholerae''. CTX is responsible for the massive, watery diarrhea characteristic of cholera i ...

(CTX), which makes cholera especially

virulent Virulence is a pathogen's or microorganism's ability to cause damage to a host. In most, especially in animal systems, virulence refers to the degree of damage caused by a microbe to its host. The pathogenicity of an organism—its ability to ...

. It can carry genes from one ''V. cholerae'' strain to another.

Genetic material

CTXφ is generally present and integrated into the

genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding g ...

of the ''V. cholerae'' bacterium, and more rarely in a

virion A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Since Dmitri Ivanovsky's ...

from outside the bacterium. While integrated into the bacterial genome, CTX prophages are found on each of the two chromosomes (in the O1 serogroup of ''V. cholerae'') or arranged in

tandem Tandem, or in tandem, is an arrangement in which a team of machines, animals or people are lined up one behind another, all facing in the same direction. The original use of the term in English was in ''tandem harness'', which is used for two ...

on the larger chromosome (in the

El Tor El Tor is a particular strain of the bacterium ''Vibrio cholerae'', the causative agent of cholera. Also known as ''V. cholerae'' biotype eltor, it has been the dominant strain in the seventh global cholera pandemic. It is distinguished from t ...

biotype of ''V. cholerae''). The genome of CTXφ is 6.9 kb long and consists of two regions. The core region contains genes that code for CTX itself and some proteins that are presumed to form the outside coat of the virus. The RS2 region contains genes that control the replication, regulation, and integration of CTXφ.

Insertion, replication, and release from host cell

The insertion of the CTXφ genetic material into the ''V. cholerae'' bacterium is mediated by two receptors. The first is the toxin-coregulated pilus (TCP), which also aids the bacterium in adhering to the intestinal cell wall. The TCP is thought to bind to the minor CTXφ coat protein OrfU. The second is the TolQRA membrane protein structure. These requirements for phage membrane binding are quite similar to those of the

Ff phages Ff phages (for ''F'' specific ''f''ilamentous phages) is a group of almost identical filamentous phage (genus ''Inovirus'') including phages f1, fd, M13 and ZJ/2, which infect bacteria bearing the F fertility factor. The virion (virus particl ...

, which infects the bacterium ''

Escherichia coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Esc ...

'' and requires the F pilus along with the TolQRA structure. In E. coli, the TolQRA acts to translocate the Ff phage into the

periplasmic space The periplasm is a concentrated gel-like matrix in the space between the inner cytoplasmic membrane and the bacterial outer membrane called the ''periplasmic space'' in gram-negative bacteria. Using cryo-electron microscopy it has been found tha ...

, where a possible membrane fusion event leads to the insertion of the Ff genome into the ''E. coli'' cytoplasm. A similar mechanism is suspected in the injection of the CTXφ genetic material into the ''V. cholerae'' cell, though further research is needed to confirm this. After ssDNA insertion into the ''V. cholerae'' cytoplasm, a complementary strand of DNA is formed in order to create the plasmid form of the viral genome, pCTX. pCTX can undergo DNA replication to create new ssDNA genomes and/or be incorporated into the bacterial genome as a prophage. Because this prophage can be present in tandem in some biotypes of ''V. cholerae'',

horizontal gene transfer Horizontal gene transfer (HGT) or lateral gene transfer (LGT) is the movement of genetic material between unicellular and/or multicellular organisms other than by the ("vertical") transmission of DNA from parent to offspring (reproduction). H ...

and vertical transmission of the added CTXφ genes are not mutually exclusive. After the production of the proteins and genomic material necessary to create new virion forms of the bacteriophage, the proteins assemble at a membranous protein complex, the EpsD secretin. Once the new ssDNA genome is inside the assembled proteins, the CTXφ virion detaches from the EpsD and is free to infect other bacteria. Phage particles are secreted from bacterial cells without lysis.

Non-CT toxins

Recent research suggests that at least two toxins other than CT are produced from genes of the CTXφ genome. The first of these is accessory cholera

enterotoxin An enterotoxin is a protein exotoxin released by a microorganism that targets the intestines. Enterotoxins are chromosomally encoded or plasmid encoded exotoxins that are produced and secreted from several bacterial organisms. They are heat la ...

(Ace). Ace is currently thought to be a minor coat protein of virion stage CTXφ, though the process by which the toxin could be released from the protein coat has not yet been identified. The second non-CT toxin encoded within the CTXφ genome is zonula occludens toxin (Zot). Zot, though absolutely essential for the production of the CTXφ virion, is not actually present in the phage particle. The part that Ace and Zot play in the

virulence Virulence is a pathogen's or microorganism's ability to cause damage to a host. In most, especially in animal systems, virulence refers to the degree of damage caused by a microbe to its host. The pathogenicity of an organism—its ability to ...

of cholera is still quite unclear.

References

{{DEFAULTSORT:CTXphi Bacteriophage Bacteriophages Inoviridae