TY - JOUR
T1 - Cryptic prophages as targets for drug development
AU - Wang, Xiaoxue
AU - Wood, Thomas K.
N1 - Funding Information:
This work was supported by the National Basic Research Program of China (Grant No. 2013CB955701 to XW), by the National Natural Science Foundation of China ( NFSC31270214 , NFSC31290233 to XW), and the Army Research Office ( W911NF-14-1-0279 to T.W.). We thank for Drs. Yunxue Guo and Pengxia Wang at the South China Sea Institute of Oceanology for their help with the table and the figure for this manuscript. XW is the recipient of the 1000-Youth Elite Program (the Recruitment Program of Global Experts in China), and TW is the Biotechnology Endowed Professor at the Pennsylvania State University.
Publisher Copyright:
© 2016 The Authors.
PY - 2016/7/1
Y1 - 2016/7/1
N2 - 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.
AB - 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.
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U2 - 10.1016/j.drup.2016.06.001
DO - 10.1016/j.drup.2016.06.001
M3 - Review article
C2 - 27449596
AN - SCOPUS:84975090294
VL - 27
SP - 30
EP - 38
JO - Drug Resistance Updates
JF - Drug Resistance Updates
SN - 1368-7646
ER -