title: Cryptic prophages as targets for drug development.
abstract: 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.
authors.affiliation: 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.
authors.forename: Xiaoxue
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Chemical Engineering, Pennsylvania State University, University Park, PA 16802-4400, United States; Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA 16802-4400, United States. Electronic address: tuw14@psu.edu.
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Wood
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity / Q000821:virology; D002876:Chromosomes, Bacterial / Q000737:chemistry / Q000821:virology*; D004352:Drug Resistance, Microbial / Q000235:genetics*; D022761:Gene Transfer, Horizontal; D016680:Genome, Bacterial; D008242:Lysogeny / Q000235:genetics; D039002:Prophages / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity; D013014:SOS Response, Genetics; D000075704:Toxin-Antitoxin Systems / Q000235:genetics; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D037521:Virulence Factors
keywords: Antibiotic resistance; Antibiotic tolerance; Cryptic prophage; Horizontal gene transfer; Toxin–antitoxin system