Reintroduction of Two Deleted Virulence Loci Restores Full Virulence to the Live Vaccine Strain of Francisella tularensis
Emelie Salomonsson,Emelie Salomonsson,Kerstin Kuoppa,Anna-Lena Forslund,Carl Zingmark,Igor Golovliov,Anders Sjöstedt,Laila Noppa,Åke Forsberg,Åke Forsberg +9 more
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TLDR
It is shown 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.Abstract:
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.read more
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Journal ArticleDOI
Cell biology and molecular ecology of Francisella tularensis
TL;DR: The past few years have witnessed a quantum leap in understanding of various aspects of this organism and this review will discuss these remarkable advances.
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The 58-kilodalton major virulence factor of Francisella tularensis is required for efficient utilization of iron.
TL;DR: The data demonstrate that the FTT0918 protein is required for F. tularensis to utilize iron bound to siderophores and that it likely has a role also in siderophile-independent iron acquisition.
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Evolution toward high-level fluoroquinolone resistance in Francisella species
Vivien Sutera,Maxime Levert,Maxime Levert,Wim P. Burmeister,Dominique Schneider,Dominique Schneider,Max Maurin,Max Maurin +7 more
TL;DR: The efficiency and speed of in vitro production of mutants highly resistant to fluoroquinolones in Francisella species emphasize the urgent need to identify all antibiotic resistance mechanisms in these species, develop molecular tools for their detection and design new therapeutic alternatives for tularaemia.
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Biofilms: an advancement in our understanding of Francisella species.
TL;DR: The role of extracellular carbohydrates and capsule, quorum sensing and two-component signaling systems in the formation of biofilms of Francisella spp. is discussed in this article.
Journal ArticleDOI
Francisella tularensis vaccines.
TL;DR: Efforts are underway to determine the basis of attenuation of LVS, and to understand the immunity required for protection, as well as alternative approaches to produce subunit vaccines and defined attenuated strains.
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