Collateral effects of antibiotics: carbadox and metronidazole induce VSH-1 and facilitate gene transfer among Brachyspira hyodysenteriae strains.
Brachyspira hyodysenteriae is an anaerobic spirochete and the etiologic agent of swine dysentery. The genome of this spirochete contains a mitomycin C-inducible, prophage-like gene transfer agent designated VSH-1. VSH-1 particles package random 7.5-kb fragments of the B. hyodysenteriae genome and transfer genes between B. hyodysenteriae cells. The chemicals and conditions inducing VSH-1 production are largely unknown. Antibiotics used in swine management and stressors inducing traditional prophages might induce VSH-1 and thereby stimulate lateral gene transfer between B. hyodysenteriae cells. In these studies, VSH-1 induction was initially detected by a quantitative real-time reverse transcriptase PCR assay evaluating increased transcription of hvp38 (VSH-1 head protein gene). VSH-1 induction was confirmed by detecting VSH-1-associated 7.5-kb DNA and VSH-1 particles in B. hyodysenteriae cultures. Nine antibiotics (chlortetracycline, lincomycin, tylosin, tiamulin, virginiamycin, ampicillin, ceftriaxone, vancomycin, and florfenicol) at concentrations affecting B. hyodysenteriae growth did not induce VSH-1 production. By contrast, VSH-1 was detected in B. hyodysenteriae cultures treated with mitomycin C (10 microg/ml), carbadox (0.5 microg/ml), metronidazole (0.5 microg/ml), and H(2)O(2) (300 microM). Carbadox- and metronidazole-induced VSH-1 particles transmitted tylosin and chloramphenicol resistance determinants between B. hyodysenteriae strains. The results of these studies suggest that certain antibiotics may induce the production of prophage or prophage-like elements by intestinal bacteria and thereby impact intestinal microbial ecology.
Stanton
Thaddeus B
TB
Pre-Harvest Food Safety and Enteric Diseases Research Unit, National Animal Disease Center, Agricultural Research Service, U.S. Department of Agriculture, Ames, Iowa 50010, USA. Thaddeus.Stanton@ars.usda.gov
Humphrey
Samuel B
SB
Sharma
Vijay K
VK
Zuerner
Richard L
RL
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001435:Bacteriophages / Q000187:drug effects / Q000254:growth & development / Q000648:ultrastructure; D017401:Brachyspira hyodysenteriae / Q000187:drug effects* / Q000235:genetics* / Q000254:growth & development / Q000821:virology; D002218:Carbadox / Q000494:pharmacology*; D003470:Culture Media / Q000737:chemistry; D004279:DNA, Viral / Q000032:analysis; D024881:Drug Resistance, Bacterial / Q000235:genetics; D005814:Genes, Viral; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008795:Metronidazole / Q000494:pharmacology*; D046529:Microscopy, Electron, Transmission; D016685:Mitomycin / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D039002:Prophages / Q000187:drug effects*; D012367:RNA, Viral / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000187:drug effects; D014161:Transduction, Genetic; D014764:Viral Proteins / Q000235:genetics
D000900:Anti-Bacterial Agents; D003470:Culture Media; D004279:DNA, Viral; D012367:RNA, Viral; D014764:Viral Proteins; D008795:Metronidazole; D016685:Mitomycin; D006861:Hydrogen Peroxide; D002218:Carbadox