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result sql = The Fischer 344 rat reflects human susceptibility to francisella pulmonary challenge and provides a new platform for virulence and protection studies.
The Fischer 344 rat reflects human susceptibility to francisella pulmonary challenge and provides a new platform for virulence and protection studies.
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char = t;code = 116
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = b;code = 98
char = r;code = 114
char = o;code = 111
char = a;code = 97
char = d;code = 100
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = g;code = 103
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = s;code = 115
char = e;code = 101
char = n;code = 110
char = s;code = 115
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = i;code = 105
char = t;code = 116
char = y;code = 121
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = p;code = 112
char = u;code = 117
char = l;code = 108
char = m;code = 109
char = o;code = 111
char = n;code = 110
char = a;code = 97
char = r;code = 114
char = y;code = 121
char = ;code = 32
char = c;code = 99
char = h;code = 104
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = e;code = 101
char = n;code = 110
char = g;code = 103
char = e;code = 101
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = h;code = 104
char = u;code = 117
char = m;code = 109
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = v;code = 118
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 = t;code = 116
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = b;code = 98
char = s;code = 115
char = p;code = 112
char = .;code = 46
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 = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = h;code = 104
char = o;code = 111
char = l;code = 108
char = a;code = 97
char = r;code = 114
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = .;code = 46
char = ;code = 32
char = U;code = 85
char = n;code = 110
char = l;code = 108
char = i;code = 105
char = k;code = 107
char = e;code = 101
char = ;code = 32
char = m;code = 109
char = i;code = 105
char = c;code = 99
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = F;code = 70
char = i;code = 105
char = s;code = 115
char = c;code = 99
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = h;code = 104
char = i;code = 105
char = g;code = 103
char = h;code = 104
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = g;code = 103
char = r;code = 114
char = e;code = 101
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = t;code = 116
char = a;code = 97
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 = p;code = 112
char = u;code = 117
char = l;code = 108
char = m;code = 109
char = o;code = 111
char = n;code = 110
char = a;code = 97
char = r;code = 114
char = y;code = 121
char = ;code = 32
char = c;code = 99
char = h;code = 104
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = e;code = 101
char = n;code = 110
char = g;code = 103
char = e;code = 101
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = L;code = 76
char = V;code = 86
char = S;code = 83
char = ;code = 32
char = (;code = 40
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = t;code = 116
char = t;code = 116
char = e;code = 101
char = n;code = 110
char = u;code = 117
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = r;code = 114
char = i;code = 105
char = v;code = 118
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = b;code = 98
char = s;code = 115
char = p;code = 112
char = .;code = 46
char = ;code = 32
char = h;code = 104
char = o;code = 111
char = l;code = 108
char = a;code = 97
char = r;code = 114
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = );code = 41
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = b;code = 98
char = s;code = 115
char = p;code = 112
char = .;code = 46
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = v;code = 118
char = i;code = 105
char = c;code = 99
char = i;code = 105
char = d;code = 100
char = a;code = 97
char = .;code = 46
char = ;code = 32
char = W;code = 87
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = B;code = 66
char = M;code = 77
char = D;code = 68
char = M;code = 77
char = ,;code = 44
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = b;code = 98
char = s;code = 115
char = p;code = 112
char = .;code = 46
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 = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = L;code = 76
char = V;code = 86
char = S;code = 83
char = ;code = 32
char = s;code = 115
char = h;code = 104
char = o;code = 111
char = w;code = 119
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = m;code = 109
char = i;code = 105
char = n;code = 110
char = i;code = 105
char = m;code = 109
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = p;code = 112
char = l;code = 108
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ,;code = 44
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = b;code = 98
char = s;code = 115
char = p;code = 112
char = .;code = 46
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = v;code = 118
char = i;code = 105
char = c;code = 99
char = i;code = 105
char = d;code = 100
char = a;code = 97
char = ;code = 32
char = s;code = 115
char = h;code = 104
char = o;code = 111
char = w;code = 119
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = r;code = 114
char = g;code = 103
char = i;code = 105
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = p;code = 112
char = l;code = 108
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = b;code = 98
char = s;code = 115
char = p;code = 112
char = .;code = 46
char = ;code = 32
char = h;code = 104
char = o;code = 111
char = l;code = 108
char = a;code = 97
char = r;code = 114
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = p;code = 112
char = l;code = 108
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = r;code = 114
char = o;code = 111
char = b;code = 98
char = u;code = 117
char = s;code = 115
char = t;code = 116
char = l;code = 108
char = y;code = 121
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = l;code = 108
char = i;code = 105
char = m;code = 109
char = i;code = 105
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = m;code = 109
char = a;code = 97
char = c;code = 99
char = r;code = 114
char = o;code = 111
char = p;code = 112
char = h;code = 104
char = a;code = 97
char = g;code = 103
char = e;code = 101
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = p;code = 112
char = l;code = 108
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = b;code = 98
char = s;code = 115
char = p;code = 112
char = .;code = 46
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 = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = v;code = 118
char = i;code = 105
char = c;code = 99
char = i;code = 105
char = d;code = 100
char = a;code = 97
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 = s;code = 115
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = r;code = 114
char = r;code = 114
char = e;code = 101
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = n;code = 110
char = i;code = 105
char = t;code = 116
char = r;code = 114
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = o;code = 111
char = x;code = 120
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = .;code = 46
char = ;code = 32
char = I;code = 73
char = m;code = 109
char = p;code = 112
char = o;code = 111
char = r;code = 114
char = t;code = 116
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = l;code = 108
char = y;code = 121
char = ,;code = 44
char = ;code = 32
char = F;code = 70
char = i;code = 105
char = s;code = 115
char = c;code = 99
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = 3;code = 51
char = 4;code = 52
char = 4;code = 52
char = ;code = 32
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = r;code = 114
char = v;code = 118
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = p;code = 112
char = u;code = 117
char = l;code = 108
char = m;code = 109
char = o;code = 111
char = n;code = 110
char = a;code = 97
char = r;code = 114
char = y;code = 121
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = f;code = 102
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = b;code = 98
char = s;code = 115
char = p;code = 112
char = .;code = 46
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = v;code = 118
char = i;code = 105
char = c;code = 99
char = i;code = 105
char = d;code = 100
char = a;code = 97
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = r;code = 114
char = k;code = 107
char = e;code = 101
char = d;code = 100
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = g;code = 103
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = s;code = 115
char = t;code = 116
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = b;code = 98
char = s;code = 115
char = e;code = 101
char = q;code = 113
char = u;code = 117
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = p;code = 112
char = u;code = 117
char = l;code = 108
char = m;code = 109
char = o;code = 111
char = n;code = 110
char = a;code = 97
char = r;code = 114
char = y;code = 121
char = ;code = 32
char = c;code = 99
char = h;code = 104
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = e;code = 101
char = n;code = 110
char = g;code = 103
char = e;code = 101
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = b;code = 98
char = s;code = 115
char = p;code = 112
char = .;code = 46
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 = 44
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = g;code = 103
char = g;code = 103
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = b;code = 98
char = s;code = 115
char = p;code = 112
char = .;code = 46
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = v;code = 118
char = i;code = 105
char = c;code = 99
char = i;code = 105
char = d;code = 100
char = a;code = 97
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = y;code = 121
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = u;code = 117
char = s;code = 115
char = e;code = 101
char = f;code = 102
char = u;code = 117
char = l;code = 108
char = ;code = 32
char = p;code = 112
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = m;code = 109
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = l;code = 108
char = o;code = 111
char = p;code = 112
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = o;code = 111
char = f;code = 102
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 = s;code = 115
char = ;code = 32
char = a;code = 97
char = g;code = 103
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = s;code = 115
char = t;code = 116
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = b;code = 98
char = s;code = 115
char = p;code = 112
char = .;code = 46
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
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = >;code = 62
char = C;code = 67
char = O;code = 79
char = N;code = 78
char = C;code = 67
char = L;code = 76
char = U;code = 85
char = S;code = 83
char = I;code = 73
char = O;code = 79
char = N;code = 78
char = S;code = 83
char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = F;code = 70
char = i;code = 105
char = s;code = 115
char = c;code = 99
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = 3;code = 51
char = 4;code = 52
char = 4;code = 52
char = ;code = 32
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
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char = s;code = 115
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char = m;code = 109
char = i;code = 105
char = l;code = 108
char = a;code = 97
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char = ;code = 32
char = s;code = 115
char = e;code = 101
char = n;code = 110
char = s;code = 115
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = i;code = 105
char = t;code = 116
char = y;code = 121
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = F;code = 70
char = .;code = 46
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 = 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 = s;code = 115
char = ;code = 32
char = a;code = 97
char = s;code = 115
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char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = p;code = 112
char = o;code = 111
char = r;code = 114
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
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char = s;code = 115
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char = ;code = 32
char = t;code = 116
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char = u;code = 117
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char = F;code = 70
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char = h;code = 104
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char = 4;code = 52
char = ;code = 32
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char = a;code = 97
char = y;code = 121
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char = m;code = 109
char = a;code = 97
char = y;code = 121
char = ;code = 32
char = s;code = 115
char = e;code = 101
char = r;code = 114
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = t;code = 116
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = i;code = 105
char = m;code = 109
char = a;code = 97
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char = ;code = 32
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char = o;code = 111
char = d;code = 100
char = e;code = 101
char = l;code = 108
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
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 = 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 = d;code = 100
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = l;code = 108
char = o;code = 111
char = p;code = 112
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = .;code = 46
result sql = BACKGROUND : The pathogenesis of Francisella tularensis, the causative agent of tularemia, has been primarily characterized in mice. However, the high degree of sensitivity of mice to bacterial challenge, especially with the human virulent strains of F. tularensis, limits this animal model for screening of defined attenuated vaccine candidates for protection studies.

METHODS AND FINDINGS : We analyzed the susceptibility of the Fischer 344 rat to pulmonary (intratracheal) challenge with three different subspecies (subsp) of F. tularensis that reflect different levels of virulence in humans, and characterized the bacterial replication profile in rat bone marrow-derived macrophages (BMDM). In contrast to the mouse, Fischer 344 rats exhibit a broader range of sensitivity to pulmonary challenge with the human virulent subsp. tularensis and holarctica. Unlike mice, Fischer rats exhibited a high degree of resistance to pulmonary challenge with LVS (an attenuated derivative of subsp. holarctica) and subsp. novicida. Within BMDM, subsp. tularensis and LVS showed minimal replication, subsp. novicida showed marginal replication, and subsp. holartica replicated robustly. The limited intramacrophage replication of subsp. tularensis and novicida strains was correlated with the induction of nitric oxide production. Importantly, Fischer 344 rats that survived pulmonary infection with subsp. novicida were markedly protected against subsequent pulmonary challenge with subsp. tularensis, suggesting that subsp. novicida may be a useful platform for the development of vaccines against subsp. tularensis.

CONCLUSIONS : The Fischer 344 rat exhibits similar sensitivity to F. tularensis strains as that reported for humans, and thus the Fischer 344 ray may serve as a better animal model for tularemia vaccine development.

Publication: PLoS ONE 2010 ;5(4)::e9952. :doi: 10.1371/journal.pone.0009952.
Publication Date: 2010
Study Author(s): Ray, Heather J;Chu, Ping;Wu, Terry H;Lyons, C Rick;Murthy, Ashlesh K;Guentzel, M Neal;Klose, Karl E;Arulanandam, Bernard P;
Institution: Department of Biology, University of Texas at San Antonio, South Texas Center for Emerging Infectious Diseases, San Antonio, Texas, United States of America.
Shortcut link to this study:
BACKGROUND : The pathogenesis of Francisella tularensis, the causative agent of tularemia, has been primarily characterized in mice. However, the high degree of sensitivity of mice to bacterial challenge, especially with the human virulent strains of F. tularensis, limits this animal model for screening of defined attenuated vaccine candidates for protection studies.

METHODS AND FINDINGS : We analyzed the susceptibility of the Fischer 344 rat to pulmonary (intratracheal) challenge with three different subspecies (subsp) of F. tularensis that reflect different levels of virulence in humans, and characterized the bacterial replication profile in rat bone marrow-derived macrophages (BMDM). In contrast to the mouse, Fischer 344 rats exhibit a broader range of sensitivity to pulmonary challenge with the human virulent subsp. tularensis and holarctica. Unlike mice, Fischer rats exhibited a high degree of resistance to pulmonary challenge with LVS (an attenuated derivative of subsp. holarctica) and subsp. novicida. Within BMDM, subsp. tularensis and LVS showed minimal replication, subsp. novicida showed marginal replication, and subsp. holartica replicated robustly. The limited intramacrophage replication of subsp. tularensis and novicida strains was correlated with the induction of nitric oxide production. Importantly, Fischer 344 rats that survived pulmonary infection with subsp. novicida were markedly protected against subsequent pulmonary challenge with subsp. tularensis, suggesting that subsp. novicida may be a useful platform for the development of vaccines against subsp. tularensis.

CONCLUSIONS : The Fischer 344 rat exhibits similar sensitivity to F. tularensis strains as that reported for humans, and thus the Fischer 344 ray may serve as a better animal model for tularemia vaccine development.
PMID: 20376351

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