INHIBITION OF YERSINIA PESTIS
The disclosure relates to the targeting of Y. pestis mediated by the binding activity of tail fibers from naturally occurring R-type pyocins from Pseudomonas aeruginosa . The targeting may be mediated by a macromolecular complex such as the pyocin itself, a high molecular weight (hmw) bacteriocin modified to have the tail fiber's binding activity, or a bacteriophage modified to have the tail fiber's binding activity. Compositions comprising such complexes are described. Also disclosed are methods for the use of a complex, such as to inhibit the growth of a Yersinia species like Y. pestis , by compromising the integrity of its cytoplasmic membrane are also described. Additional methods include use of the binding activity to identify Y. pestis.
1 . A method of inhibiting growth of Y. pestis , said method comprising contacting said Y. pestis with an isolated R-type pyocin which binds thereto.
2 . The method of claim 1 , wherein contacting kills said Y. pestis.
3 . The method of claim 1 , wherein said pyocin is an R2, R4, or R5 type pyocin.
4 . The method of claim 1 , further comprising contacting said Y. pestis with an antibiotic.
5 . The method of claim 1 , wherein said contacting occurs in vivo or in vitro.
6 . The method of claim 5 , wherein said contacting occurs in vivo and bacteria are present in a human patient or an animal subject.
7 . The method of claim 6 , wherein said animal subject is an arthropod of the genus Xenopsylla or a flea.
8 . The method of claim 5 , wherein said contacting is in vitro; said Y. pestis is present on a surface of an inanimate object; and said contacting decontaminates said surface by killing the Y. pestis.
9 . The method of claim 6 , wherein said contacting comprises administering said pyocin to said patient or subject.
10 . The method of claim 9 , wherein said pyocin is in a composition comprising a pharmaceutically acceptable excipient.
11 . The method of claim 10 , wherein said composition is formulated for administration by an oral, topical, or inhalation route.
12 . A method of inhibiting growth of Y. pestis , said method comprising contacting Y. pestis with a recombinant bacteriophage comprising a receptor binding domain from an R-type pyocin.
13 . A method of inoculating a subject, said method comprising administering to said subject, recombinant bacteria which express a recombinant bacteriophage or hmw bacteriocin comprising a receptor binding domain (RBD) from an R-type pyocin.
14 . The method of claim 13 , wherein said RBD is that of an R2, R4, or R5 type pyocin.
15 . The method of claim 14 , wherein said bacteriophage is a myoviridiae family member, optionally selected from P2, P4, ΦA1122, ΦL-413c and VHML.
16 . The method of claim 15 , wherein said subject is a human being, a mammalian animal, or an arthropod.
17 . The method of claim 16 , wherein said animal subject is an arthropod of the genus Xenopsylla or a flea.
18 . A method of deactivating a bioweapon comprising Y. pestis , said method comprising contacting said bioweapon with an R-type pyocin which compromises the integrity of a Y. pestis cytoplasmic membrane.
19 . A composition comprising an R-type pyocin and a Yersinia inhibiting antibiotic.
20 . The composition of claim 19 , wherein said pyocin is an isolated or recombinant R-type pyocin.
21 . The composition of claim 20 , wherein said R-type pyocin is an R2, R4, or R5 type pyocin.
22 . The composition of claim 21 , wherein said antibiotic is doxycycline, streptomycin, gentamicin, or ciprofloxacin.
23 . A method of detecting the presence of Y. pestis in a sample suspected of containing Y. pestis , said method comprising
contacting a sample with a detectably labeled R-type pyocin which binds Y. pestis to form a complex, and
detecting said complex as an indicator of the presence of Y. pestis.
24 . The method of claim 23 , wherein the sample is further suspected to contain one or more Yersinia species.
25 . The method of claim 24 , wherein the Yersinia species is Y. enterocolitica, Y. fredericksenii , and/or Y. pseudotuberculosis.
26 . A method of detecting the presence of Y. pestis in a sample suspected of containing Y. pestis , said method comprising
contacting a sample, with an R-type pyocin which compromises the integrity of the cytoplasmic membrane of Y. pestis , and
detecting the release of one or more intercellular components from said Y. pestis as an indicator of the presence of Y. pestis.
27 . The method of claim 26 , wherein the sample is further suspected to contain one or more Yersinia species.
28 . The method of claim 27 , wherein the Yersinia species is Y. enterocolitica, Y. fredericksenii , and/or Y. pseudotuberculosis.