A bacteriolytic agent that detects and kills Bacillus anthracis.
The dormant and durable spore form of Bacillus anthracis is an ideal biological weapon of mass destruction. Once inhaled, spores are transported by alveolar macrophages to lymph nodes surrounding the lungs, where they germinate; subsequent vegetative expansion causes an overwhelming flood of bacteria and toxins into the blood, killing up to 99% of untreated victims. Natural and genetically engineered antibiotic-resistant bacilli amplify the threat of spores being used as weapons, and heighten the need for improved treatments and spore-detection methods after an intentional release. We exploited the inherent binding specificity and lytic action of bacteriophage enzymes called lysins for the rapid detection and killing of B. anthracis. Here we show that the PlyG lysin, isolated from the gamma phage of B. anthracis, specifically kills B. anthracis isolates and other members of the B. anthracis 'cluster' of bacilli in vitro and in vivo. Both vegetative cells and germinating spores are susceptible. The lytic specificity of PlyG was also exploited as part of a rapid method for the identification of B. anthracis. We conclude that PlyG is a tool for the treatment and detection of B. anthracis.
Laboratory of Bacteriql Pathogenesis and Immunology, The Rockefeller University, New York, New York 10021, USA.
Raymond
R
Schuch
Daniel
D
Nelson
Vincent A
VA
Fischetti
D000595:Amino Acid Sequence; D000818:Animals; D000881:Anthrax / Q000175:diagnosis* / Q000188:drug therapy* / Q000382:microbiology; D001408:Bacillus anthracis / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification / Q000821:virology*; D001433:Bacteriolysis / Q000187:drug effects; D001435:Bacteriophages / Q000737:chemistry*; D001694:Biological Warfare / Q000517:prevention & control; D023482:Bioterrorism / Q000517:prevention & control; D004195:Disease Models, Animal; D024881:Drug Resistance, Bacterial; D006867:Hydrolases / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology* / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009238:N-Acetylmuramoyl-L-alanine Amidase; D012680:Sensitivity and Specificity; D016415:Sequence Alignment; D013171:Spores, Bacterial / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification / Q000821:virology; D013379:Substrate Specificity; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use
D014764:Viral Proteins; D006867:Hydrolases; C465450:PlyG lysin, gamma phage; D009238:N-Acetylmuramoyl-L-alanine Amidase