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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = w;code = 119
char = o;code = 111
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char = d;code = 100
char = e;code = 101
char = l;code = 108
char = e;code = 101
char = t;code = 116
char = e;code = 101
char = d;code = 100
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char = i;code = 105
char = r;code = 114
char = u;code = 117
char = l;code = 108
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
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char = l;code = 108
char = o;code = 111
char = c;code = 99
char = i;code = 105
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = f;code = 102
char = u;code = 117
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = v;code = 118
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char = r;code = 114
char = u;code = 117
char = l;code = 108
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = l;code = 108
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = v;code = 118
char = a;code = 97
char = c;code = 99
char = c;code = 99
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = F;code = 70
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = i;code = 105
char = s;code = 115
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = a;code = 97
char = ;code = 32
char = t;code = 116
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = r;code = 114
char = e;code = 101
char = n;code = 110
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = .;code = 46
result sql = Reintroduction of two deleted virulence loci restores full virulence to the live vaccine strain of Francisella tularensis.
Reintroduction of two deleted virulence loci restores full virulence to the live vaccine strain of Francisella tularensis.
char = A;code = 65
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char = a;code = 97
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char = g;code = 103
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char = a;code = 97
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char = o;code = 111
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char = c;code = 99
char = c;code = 99
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char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = g;code = 103
char = e;code = 101
char = n;code = 110
char = e;code = 101
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char = c;code = 99
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char = e;code = 101
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char = t;code = 116
char = s;code = 115
char = ;code = 32
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char = n;code = 110
char = g;code = 103
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char = i;code = 105
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char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = a;code = 97
char = t;code = 116
char = t;code = 116
char = e;code = 101
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char = u;code = 117
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = t;code = 116
char = e;code = 101
char = n;code = 110
char = ;code = 32
char = l;code = 108
char = a;code = 97
char = r;code = 114
char = g;code = 103
char = e;code = 101
char = l;code = 108
char = y;code = 121
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char = u;code = 117
char = n;code = 110
char = k;code = 107
char = n;code = 110
char = o;code = 111
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char = n;code = 110
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char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = r;code = 114
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char = e;code = 101
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char = s;code = 115
char = i;code = 105
char = o;code = 111
char = n;code = 110
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char = t;code = 116
char = o;code = 111
char = ;code = 32
char = v;code = 118
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char = r;code = 114
char = u;code = 117
char = l;code = 108
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = n;code = 110
char = o;code = 111
char = t;code = 116
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char = b;code = 98
char = e;code = 101
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = c;code = 99
char = l;code = 108
char = u;code = 117
char = d;code = 100
char = e;code = 101
char = d;code = 100
char = .;code = 46
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char = I;code = 73
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = 1;code = 49
char = 9;code = 57
char = 5;code = 53
char = 0;code = 48
char = s;code = 115
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char = ;code = 32
char = a;code = 97
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char = l;code = 108
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char = e;code = 101
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char = v;code = 118
char = a;code = 97
char = c;code = 99
char = c;code = 99
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char = n;code = 110
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char = s;code = 115
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char = r;code = 114
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = ,;code = 44
char = ;code = 32
char = L;code = 76
char = V;code = 86
char = S;code = 83
char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = d;code = 100
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char = v;code = 118
char = e;code = 101
char = l;code = 108
char = o;code = 111
char = p;code = 112
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = f;code = 102
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = t;code = 116
char = y;code = 121
char = p;code = 112
char = e;code = 101
char = ;code = 32
char = B;code = 66
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = i;code = 105
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char = o;code = 111
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char = F;code = 70
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char = l;code = 108
char = a;code = 97
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char = t;code = 116
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char = a;code = 97
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char = i;code = 105
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = u;code = 117
char = s;code = 115
char = a;code = 97
char = t;code = 116
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char = e;code = 101
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char = a;code = 97
char = g;code = 103
char = e;code = 101
char = n;code = 110
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = r;code = 114
char = e;code = 101
char = m;code = 109
char = i;code = 105
char = a;code = 97
char = .;code = 46
char = ;code = 32
char = L;code = 76
char = V;code = 86
char = S;code = 83
char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = h;code = 104
char = i;code = 105
char = c;code = 99
char = h;code = 104
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = h;code = 104
char = i;code = 105
char = g;code = 103
char = h;code = 104
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = a;code = 97
char = t;code = 116
char = t;code = 116
char = e;code = 101
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char = u;code = 117
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = h;code = 104
char = u;code = 117
char = m;code = 109
char = a;code = 97
char = n;code = 110
char = s;code = 115
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char = b;code = 98
char = u;code = 117
char = t;code = 116
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = v;code = 118
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char = r;code = 114
char = u;code = 117
char = l;code = 108
char = e;code = 101
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char = t;code = 116
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = m;code = 109
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char = c;code = 99
char = e;code = 101
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char = b;code = 98
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char = i;code = 105
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char = f;code = 102
char = e;code = 101
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char = ;code = 32
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char = u;code = 117
char = t;code = 116
char = e;code = 101
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char = ,;code = 44
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char = h;code = 104
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = b;code = 98
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char = e;code = 101
char = n;code = 110
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char = e;code = 101
char = x;code = 120
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char = e;code = 101
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char = e;code = 101
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char = ;code = 32
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char = p;code = 112
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char = a;code = 97
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char = f;code = 102
char = ;code = 32
char = f;code = 102
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char = m;code = 109
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char = l;code = 108
char = a;code = 97
char = b;code = 98
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char = .;code = 46
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char = T;code = 84
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char = e;code = 101
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char = V;code = 86
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result sql = A disadvantage of several old vaccines is that the genetic events resulting in the attenuation are often largely unknown and reversion to virulence cannot be excluded. In the 1950s, a live vaccine strain, LVS, was developed from a type B strain of Francisella tularensis, the causative agent of tularemia. LVS, which is highly attenuated for humans but still virulent for mice by some infection routes, has been extensively studied and found to protect staff from laboratory-acquired tularemia. The efforts to improve biopreparedness have identified a demand for a vaccine against tularemia. Recently the rapid progress in genomics of different Francisella strains has led to identification of several regions of differences (RDs). Two genes carried within RDs, pilA, encoding a putative type IV pilin, and FTT0918, encoding an outer membrane protein, have been linked to virulence. Interestingly, LVS has lost these two genes via direct repeat-mediated deletions. Here we show that reintroduction of the two deleted regions restores virulence of LVS in a mouse infection model to a level indistinguishable from that of virulent type B strains. The identification of the two attenuating deletion events could facilitate the licensing of LVS for use in humans.

Publication: Infect. Immun. 2009 Aug ;77(8)::3424-31. :doi: 10.1128/IAI.00196-09.
Publication Date: 2009 Aug
Study Author(s): Salomonsson, Emelie;Kuoppa, Kerstin;Forslund, Anna-Lena;Zingmark, Carl;Golovliov, Igor;Sjöstedt, Anders;Noppa, Laila;Forsberg, Ake;
Institution: FOI Swedish Defence Research Agency, Division of CBRN Defence and Security, Umeå, Sweden.
Shortcut link to this study:
A disadvantage of several old vaccines is that the genetic events resulting in the attenuation are often largely unknown and reversion to virulence cannot be excluded. In the 1950s, a live vaccine strain, LVS, was developed from a type B strain of Francisella tularensis, the causative agent of tularemia. LVS, which is highly attenuated for humans but still virulent for mice by some infection routes, has been extensively studied and found to protect staff from laboratory-acquired tularemia. The efforts to improve biopreparedness have identified a demand for a vaccine against tularemia. Recently the rapid progress in genomics of different Francisella strains has led to identification of several regions of differences (RDs). Two genes carried within RDs, pilA, encoding a putative type IV pilin, and FTT0918, encoding an outer membrane protein, have been linked to virulence. Interestingly, LVS has lost these two genes via direct repeat-mediated deletions. Here we show that reintroduction of the two deleted regions restores virulence of LVS in a mouse infection model to a level indistinguishable from that of virulent type B strains. The identification of the two attenuating deletion events could facilitate the licensing of LVS for use in humans.
PMID: 19506014

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