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1 F. tularensis activates complement, and recent data sugg
2 F. tularensis also significantly impaired apoptosis trig
3 F. tularensis and B. anthracis were grown in liquid brot
4 F. tularensis DNA in buffer or CFU of F. tularensis was
5 F. tularensis has long been developed as a biological we
6 F. tularensis infects leukocytes and exhibits an extrace
7 F. tularensis LVS::Deltawzy expressed only 1 repeating u
8 F. tularensis represses inflammasome; a cytosolic multi-
9 F. tularensis subspecies encode a series of acid phospha
10 F. tularensis subspecies holarctica was isolated from th
11 F. tularensis Types A and B form poor biofilms, but F. t
12 F. tularensis virulence stems from genes encoded on the
13 eriments in F. tularensis identified over 50 F. tularensis DsbA substrates, including outer membrane
15 ainst aerosol challenge with virulent type A F. tularensis in a species other than a rodent since the
16 7 is dispensable for host immunity to type A F. tularensis infection, and that induced and protective
19 In contrast, infection of macrophages with a F. tularensis LVS rluD pseudouridine synthase (FTL_0699)
22 roader spectrum of growth inhibition against F. tularensis , Bacillus anthracis , and Staphylococcus
23 y potential correlates of protection against F. tularensis and to expand and refine a comprehensive s
25 nous interleukin 12 (IL-12) protects against F. tularensis infection; this protection was lost in MII
30 Furthermore, sequencing of the amplified F. tularensis targets provides clade confirmation and in
32 ole of OAg size in protection, we created an F. tularensis live vaccine strain (LVS) mutant with a si
37 holarctica (also referred to as type B), and F. tularensis subsp. mediasiatica, as well as opportunis
39 othenate pathway in Francisella novicida and F. tularensis and identified an unknown and previously u
40 s in human virulence between F. novicida and F. tularensis may be due in part to the absence of cdGMP
42 Such outbreaks are exceedingly rare, and F. tularensis is seldom recovered from clinical specimen
45 en identified 95 lung infectivity-associated F. tularensis genes, including those encoding the Lon an
47 tion of antibodies from patients with type B F. tularensis infections and that these can be used for
48 rensis Types A and B form poor biofilms, but F. tularensis mutants lacking lipopolysaccharide O-antig
50 ecessary for classical pathway activation by F. tularensis in nonimmune human serum nor the receptors
51 veals novel pathogenic mechanisms adopted by F. tularensis to modulate macrophage innate immune funct
52 tularensis vs Pseudomonas aeruginosa and by F. tularensis live bacteria vs the closely related bacte
53 e previous reports, induction of IFN-beta by F. tularensis was not required for activation of the inf
54 hat metabolic reprogramming of host cells by F. tularensis is a key component of both inhibition of h
55 ector memory (EM) CD4(+) T cells elicited by F. tularensis infection (postimmunization) is increased
56 e FabI enoyl-ACP-reductase enzyme encoded by F. tularensis is essential and not bypassed by exogenous
60 ation of host cell death during infection by F. tularensis and highlight how shifts in the magnitude
64 iously demonstrated that PGE(2) synthesis by F. tularensis-infected macrophages requires cytosolic ph
65 White (NZW) rabbits with aerosols containing F. tularensis We evaluated the relative humidity, aeroso
67 VOCs from their fully virulent counterparts, F. tularensis subspecies tularensis strain SCHU S4 and B
68 (live vaccine strain) or catalase-deficient F. tularensis (DeltakatG) show distinct profiles in thei
69 new cartridge-based assay can rapidly detect F. tularensis in bloodstream infections directly in whol
71 tection against challenge with two different F. tularensis subsp. holarctica (type B) live vaccine st
73 erosolizable nature and low infectious dose, F. tularensis is classified as a category A select agent
78 .n., with MAb-iFT immune complexes, enhances F. tularensis-specific immune responses and protection a
80 y, human neutrophil uptake of GFP-expressing F. tularensis strains live vaccine strain and Schu S4 wa
81 nes, immunotherapeutics, and diagnostics for F. tularensis requires a detailed knowledge of the sacch
83 nicity island genes tested are essential for F. tularensis Schu S4 virulence and further suggest that
89 ent delay in host cell death is required for F. tularensis to preserve its intracellular replicative
92 Moreover, p38 MAPK activity is required for F. tularensis-induced COX-2 protein synthesis, but not f
96 vel bacterial carboxylesterase (FTT258) from F. tularensis, a homologue of human acyl protein thioest
97 signal transducer and model drug by LPS from F. tularensis vs Pseudomonas aeruginosa and by F. tulare
98 and subsp. holarctica (type B) strains from F. tularensis subsp. novicida and other near neighbors,
101 The methods currently available to genotype F. tularensis cannot conclusively identify the associate
102 rately detect and identify the hypervirulent F. tularensis subsp. tularensis subtype A.I, the virulen
105 . tularensis subsp. tularensis subtype A.II, F. tularensis subsp. holarctica (also referred to as typ
106 atty acid biosynthetic components encoded in F. tularensis are transcriptionally active during infect
108 tern of endogenous protein-tagging events in F. tularensis that are likely to be a universal feature
110 gh molecular weight (VHMW)] by expressing in F. tularensis a heterologous chain-length regulator gene
111 described as virulence-associated factors in F. tularensis Identification of these Lon substrates has
112 and FTT_0615c, the homologue of FTL_0883 in F. tularensis subsp. tularensis Schu S4 (Schu S4), elici
114 is also required for lipid A modification in F. tularensis as well as Bordetella bronchiseptica.
115 Analysis of the MglA and SspA mutants in F. tularensis reveals that interaction between PigR and
117 S transporters may play an important role in F. tularensis pathogenesis and serve as good targets for
120 susceptible than IgA(+/+) mice to intranasal F. tularensis LVS infection, despite developing higher l
121 ase, implicate the enzyme as a potential key F. tularensis effector protein, and may help elucidate a
122 membrane protein 2 localization with labeled F. tularensis in the lungs was greater in wild-type than
123 s involved in bacterial immune evasion, like F. tularensis clpB, can serve as a model for the rationa
126 Collectively, this study reports a novel F. tularensis factor that is required for innate immune
127 pic differences by evaluating the ability of F. tularensis and F. novicida to degrade chitin analogs
129 echanism of immune evasion is the ability of F. tularensis to induce the synthesis of the small lipid
133 wever, the factors that govern adaptation of F. tularensis to the intrahepatocytic niche have not bee
134 del wherein the immunomodulatory capacity of F. tularensis relies, at least in part, on TolC-secreted
136 The outbreak was caused by diverse clones of F. tularensis that occurred concomitantly, were widespre
137 ypothesized that the antioxidant defenses of F. tularensis maintain redox homeostasis in infected mac
138 multiplex nested PCR assay for detection of F. tularensis, B. anthracis, and Y. pestis directly from
139 curate identification and differentiation of F. tularensis subpopulations during epidemiological inve
140 We demonstrate that antioxidant enzymes of F. tularensis prevent the activation of redox-sensitive
143 ur results also demonstrate that FTL_0325 of F. tularensis impacts proIL-1beta expression as early as
144 ) form of the enzyme and inhibited growth of F. tularensis SchuS4 at concentrations near that of thei
146 reased cell death with a 2-3 log increase of F. tularensis replication, but could be rescued with rIL
148 y and was applicable to multiple isolates of F. tularensis Further improvements in the accuracy and p
149 screening a transposon insertion library of F. tularensis LVS in the presence of hydrogen peroxide,
150 re region of the lipopolysaccharide (LPS) of F. tularensis to probe antigenic responses elicited by a
151 profile of the live vaccine strain (LVS) of F. tularensis grown in the FL83B murine hepatocytic cell
152 nfection by the live vaccine strain (LVS) of F. tularensis Resistance is characterized by reduced let
153 f mice with the live vaccine strain (LVS) of F. tularensis, splenic IL-10 levels increased rapidly an
156 ovide fundamental insight into mechanisms of F. tularensis phagocytosis and support a model whereby n
160 Significantly, trans-translation mutants of F. tularensis are impaired in replication within macroph
161 lipopolysaccharide (LPS) O antigen (OAg) of F. tularensis has been considered for use in a glycoconj
163 ays an important role in the pathogenesis of F. tularensis and suggest that a focus on the developmen
166 surface capsular and O-Ag polysaccharides of F. tularensis and initiates the classical complement cas
167 y, whole-genome transcriptional profiling of F. tularensis with DNA microarrays from infected tissues
169 r studies, using a virulent type A strain of F. tularensis (SchuS4), indicate that IL-17Ralpha(-/-) m
171 s study, the highly human virulent strain of F. tularensis SCHU S4 and the live vaccine strain were u
172 lenge with both type A and type B strains of F. tularensis and induced functional immunity through bo
175 ether biofilm formation enhances survival of F. tularensis in aquatic or other environmental niches h
178 the uptake and intracellular trafficking of F. tularensis Live Vaccine Strain (LVS) and LVS with dis
180 asked whether complement-dependent uptake of F. tularensis strain SCHU S4 affects the survival of pri
183 We propose that the extreme virulence of F. tularensis is partially due to the bifunctional natur
185 ubsp. mediasiatica, as well as opportunistic F. tularensis subsp. novicida from each other and near n
186 gs indicate that recognition of C3-opsonized F. tularensis, but not extensive cytosolic replication,
187 ted in concert for phagocytosis of opsonized F. tularensis by human neutrophils, whereas CR3 and CR4
189 the presence of complement, whereas parental F. tularensis LVS is internalized within spacious pseudo
191 have now evaluated the lethality of primary F. tularensis live vaccine strain (LVS) pulmonary infect
193 te processes in the lung following pulmonary F. tularensis infection and provide additional insight i
196 We found that the lethality of pulmonary F. tularensis LVS infection was exacerbated under condit
199 ld-type mice highly sensitive to respiratory F. tularensis infection, and depletion beginning at 3 da
200 eutrophil niche in CD200R(-/-) mice restores F. tularensis infection to levels seen in wild-type mice
202 Despite the monomorphic nature of sequenced F. tularensis genomes, there is a significant degree of
204 ysis probe, providing sensitive and specific F. tularensis subspecies and subtype identification in a
205 Gr-1(+) CD11b(+) cells in mice that survived F. tularensis infection also suggests a potential role f
206 gs of mice infected with the LVS rather than F. tularensis type A, while IL-23p19 mRNA expression was
207 S represses inflammasome activation and that F. tularensis-encoded FTL_0325 mediates this effect.
212 ur findings provide compelling evidence that F. tularensis catalase restricts reactive oxygen species
213 lectively, this study provides evidence that F. tularensis LVS represses inflammasome activation and
218 rly infection has led to the suggestion that F. tularensis evades detection by host innate immune sur
222 nuated Listeria monocytogenes expressing the F. tularensis immunoprotective antigen IglC) as the boos
226 ate that AcpA, which contributes most of the F. tularensis acid phosphatase activity, is secreted int
227 and RNA-Seq we identify those regions of the F. tularensis chromosome occupied by PmrA and those gene
228 associates with 252 distinct regions of the F. tularensis chromosome, but exerts regulatory effects
229 erein we report the crystal structure of the F. tularensis FabI enzyme in complex with our most activ
230 identified TolC as a virulence factor of the F. tularensis live vaccine strain (LVS) and demonstrated
232 xperiments identified five substrates of the F. tularensis Lon protease (FTL578, FTL663, FTL1217, FTL
235 thereby contributing to the survival of the F. tularensis subsp. holarctica live vaccine strain (LVS
236 ogy revealed that the immune response to the F. tularensis mutant strains was significantly different
238 growth, leading us to hypothesize that these F. tularensis mutants are attenuated because they induce
239 results demonstrate that trpB contributes to F. tularensis virulence by enabling intracellular growth
240 ophages and other cell types are critical to F. tularensis pathogenesis, and impaired intracellular s
242 critical and novel regulator of immunity to F. tularensis LVS infection, its effects were masked dur
243 g the mechanisms that recruit neutrophils to F. tularensis-infected lungs, opsonization and phagocyto
245 ch literature exists on the host response to F. tularensis infection, the vast majority of work has b
251 L-17Ralpha(-/-) mice are more susceptible to F. tularensis LVS infection, our studies, using a virule
252 re by bacterial taxa Francisella tularensis (F. tularensis) subspecies novicida and Bacillus anthraci
253 facultative anaerobe Francisella tularensis: F. tularensis subsp. tularensis (type A) and F. tularens
254 ile the observed profiles of each of the two F. tularensis and B. anthracis strains exhibited some si
256 age growth that can be restored to wild-type F. tularensis LVS levels by either transcomplementation,
257 tive than the currently available unlicensed F. tularensis live vaccine strain (LVS) is needed to pro
261 monstrate that lipids enriched from virulent F. tularensis strain SchuS4, but not attenuated live vac
263 FtlC and SilC, present in the fully virulent F. tularensis Schu S4 strain for their contributions to
264 doses (LD50) of aerosolized highly virulent F. tularensis Schu S4 had a significantly higher surviva
265 on, both F. novicida and the highly virulent F. tularensis subsp. tularensis Schu S4 strain are able
266 e challenged via aerosol with human-virulent F. tularensis SCHU S4 that had been cultivated in either
268 to detect and distinguish the more virulent F. tularensis subsp. tularensis (subtypes A.I and A.II)
270 In this study, we demonstrate that virulent F. tularensis impairs production of inflammatory cytokin
271 In this study, we demonstrated that virulent F. tularensis strain SchuS4 selectively inhibits product
272 25 and its ortholog FTT0831c in the virulent F. tularensis SchuS4 strain in intramacrophage survival
274 subsp. tularensis subtype A.I, the virulent F. tularensis subsp. tularensis subtype A.II, F. tularen
281 However, the molecular mechanisms by which F. tularensis DsbA contributes to virulence are unknown.
284 Our understanding of the mechanisms by which F. tularensis senses and adapts to host environments is
285 lla factors and the mechanisms through which F. tularensis mediates these suppressive effects remain
286 unosensor formats for the detection of whole F. tularensis bacteria were developed and their performa
288 nged survival upon subsequent challenge with F. tularensis Schu S4 and provided complete protection a
289 onses generated in macrophages infected with F. tularensis live vaccine strain (LVS) or the virulent
290 ved monocytes and neutrophils, infected with F. tularensis LVS ex vivo, display enhanced restriction
292 ified from the spleens of mice infected with F. tularensis suppressed polyclonal T-cell proliferation
295 ve immunity against pulmonary infection with F. tularensis live vaccine strain, its production is tig