Cryptic prophages as targets for drug development. 2016

Xiaoxue Wang, and Thomas K Wood
Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, PR China. Electronic address: xxwang@scsio.ac.cn.

Bacterial chromosomes may contain up to 20% phage DNA that encodes diverse proteins ranging from those for photosynthesis to those for autoimmunity; hence, phages contribute greatly to the metabolic potential of pathogens. Active prophages carrying genes encoding virulence factors and antibiotic resistance can be excised from the host chromosome to form active phages and are transmissible among different bacterial hosts upon SOS responses. Cryptic prophages are artifacts of mutagenesis in which lysogenic phage are captured in the bacterial chromosome: they may excise but they do not form active phage particles or lyse their captors. Hence, cryptic prophages are relatively permanent reservoirs of genes, many of which benefit pathogens, in ways we are just beginning to discern. Here we explore the role of active prophage- and cryptic prophage-derived proteins in terms of (i) virulence, (ii) antibiotic resistance, and (iii) antibiotic tolerance; antibiotic tolerance occurs as a result of the non-heritable phenotype of dormancy which is a result of activation of toxins of toxin/antitoxin loci that are frequently encoded in cryptic prophages. Therefore, cryptic prophages are promising targets for drug development.

UI MeSH Term Description Entries
D008242 Lysogeny The phenomenon by which a temperate phage incorporates itself into the DNA of a bacterial host, establishing a kind of symbiotic relation between PROPHAGE and bacterium which results in the perpetuation of the prophage in all the descendants of the bacterium. Upon induction (VIRUS ACTIVATION) by various agents, such as ultraviolet radiation, the phage is released, which then becomes virulent and lyses the bacterium. Integration, Prophage,Prophage Integration,Integrations, Prophage,Prophage Integrations
D002876 Chromosomes, Bacterial Structures within the nucleus of bacterial cells consisting of or containing DNA, which carry genetic information essential to the cell. Bacterial Chromosome,Bacterial Chromosomes,Chromosome, Bacterial
D004352 Drug Resistance, Microbial The ability of microorganisms, especially bacteria, to resist or to become tolerant to chemotherapeutic agents, antimicrobial agents, or antibiotics. This resistance may be acquired through gene mutation or foreign DNA in transmissible plasmids (R FACTORS). Antibiotic Resistance,Antibiotic Resistance, Microbial,Antimicrobial Resistance, Drug,Antimicrobial Drug Resistance,Antimicrobial Drug Resistances,Antimicrobial Resistances, Drug,Drug Antimicrobial Resistance,Drug Antimicrobial Resistances,Drug Resistances, Microbial,Resistance, Antibiotic,Resistance, Drug Antimicrobial,Resistances, Drug Antimicrobial
D000075704 Toxin-Antitoxin Systems Mechanisms that allow bacteria and archaea to rapidly adapt to changing environmental conditions via a toxin, produced during adverse conditions, that inhibits a specific vital process, and a partner antitoxin that blocks the effects of the toxin, under normal growth conditions. System, Toxin-Antitoxin,Systems, Toxin-Antitoxin,Toxin Antitoxin Systems,Toxin-Antitoxin System
D000900 Anti-Bacterial Agents Substances that inhibit the growth or reproduction of BACTERIA. Anti-Bacterial Agent,Anti-Bacterial Compound,Anti-Mycobacterial Agent,Antibacterial Agent,Antibiotics,Antimycobacterial Agent,Bacteriocidal Agent,Bacteriocide,Anti-Bacterial Compounds,Anti-Mycobacterial Agents,Antibacterial Agents,Antibiotic,Antimycobacterial Agents,Bacteriocidal Agents,Bacteriocides,Agent, Anti-Bacterial,Agent, Anti-Mycobacterial,Agent, Antibacterial,Agent, Antimycobacterial,Agent, Bacteriocidal,Agents, Anti-Bacterial,Agents, Anti-Mycobacterial,Agents, Antibacterial,Agents, Antimycobacterial,Agents, Bacteriocidal,Anti Bacterial Agent,Anti Bacterial Agents,Anti Bacterial Compound,Anti Bacterial Compounds,Anti Mycobacterial Agent,Anti Mycobacterial Agents,Compound, Anti-Bacterial,Compounds, Anti-Bacterial
D001419 Bacteria One of the three domains of life (the others being Eukarya and ARCHAEA), also called Eubacteria. They are unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. Bacteria can be classified by their response to OXYGEN: aerobic, anaerobic, or facultatively anaerobic; by the mode by which they obtain their energy: chemotrophy (via chemical reaction) or PHOTOTROPHY (via light reaction); for chemotrophs by their source of chemical energy: CHEMOLITHOTROPHY (from inorganic compounds) or chemoorganotrophy (from organic compounds); and by their source for CARBON; NITROGEN; etc.; HETEROTROPHY (from organic sources) or AUTOTROPHY (from CARBON DIOXIDE). They can also be classified by whether or not they stain (based on the structure of their CELL WALLS) with CRYSTAL VIOLET dye: gram-negative or gram-positive. Eubacteria
D013014 SOS Response, Genetics An error-prone mechanism or set of functions for repairing damaged microbial DNA. SOS functions (a concept reputedly derived from the SOS of the international distress signal) are involved in DNA repair and mutagenesis, in cell division inhibition, in recovery of normal physiological conditions after DNA repair, and possibly in cell death when DNA damage is extensive. SOS Response (Genetics),SOS Box,SOS Function,SOS Induction,SOS Region,SOS Repair,SOS Response,SOS System,Box, SOS,Function, SOS,Functions, SOS,Genetics SOS Response,Genetics SOS Responses,Induction, SOS,Inductions, SOS,Region, SOS,Regions, SOS,Repair, SOS,Repairs, SOS,Response, Genetics SOS,Response, SOS,Response, SOS (Genetics),Responses, Genetics SOS,Responses, SOS,Responses, SOS (Genetics),SOS Functions,SOS Inductions,SOS Regions,SOS Repairs,SOS Responses,SOS Responses (Genetics),SOS Responses, Genetics,SOS Systems,System, SOS,Systems, SOS
D014774 Virulence The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. The pathogenic capacity of an organism is determined by its VIRULENCE FACTORS. Pathogenicity
D016680 Genome, Bacterial The genetic complement of a BACTERIA as represented in its DNA. Bacterial Genome,Bacterial Genomes,Genomes, Bacterial
D022761 Gene Transfer, Horizontal The naturally occurring transmission of genetic information between organisms, related or unrelated, circumventing parent-to-offspring transmission. Horizontal gene transfer may occur via a variety of naturally occurring processes such as GENETIC CONJUGATION; GENETIC TRANSDUCTION; and TRANSFECTION. It may result in a change of the recipient organism's genetic composition (TRANSFORMATION, GENETIC). Gene Transfer, Lateral,Horizontal Gene Transfer,Lateral Gene Transfer,Recombination, Interspecies,Recombination, Interspecific,Gene Transfers, Lateral,Interspecies Recombination,Interspecific Recombination,Lateral Gene Transfers

Related Publications

Xiaoxue Wang, and Thomas K Wood
December 1987, Journal of molecular biology,
Xiaoxue Wang, and Thomas K Wood
December 2022, International journal of molecular sciences,
Xiaoxue Wang, and Thomas K Wood
January 2020, Methods in molecular biology (Clifton, N.J.),
Xiaoxue Wang, and Thomas K Wood
June 2003, Drug news & perspectives,
Xiaoxue Wang, and Thomas K Wood
December 1992, Journal of hypertension. Supplement : official journal of the International Society of Hypertension,
Xiaoxue Wang, and Thomas K Wood
August 2009, Current protein & peptide science,
Xiaoxue Wang, and Thomas K Wood
January 1992, Clinical and experimental pharmacology & physiology,
Xiaoxue Wang, and Thomas K Wood
December 2016, Nucleic acids research,
Xiaoxue Wang, and Thomas K Wood
January 1994, Pharmacology & therapeutics,
Xiaoxue Wang, and Thomas K Wood
January 2014, Nature reviews. Gastroenterology & hepatology,
Copied contents to your clipboard!