Variability of the Protein Sequences of LcrV Between Epidemic and Atypical Rhamnose-Positive Strains of Yersinia pestis

Anisimov, Andrey P.; Panfertsev, E. A.; Светоч, Т. Э.; Dentovskaya, Svetlana V.

doi:10.1007/978-0-387-72124-8_3

Cited by 10 publications

(7 citation statements)

References 14 publications

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“…This classification of the LcrV types accounted for the polymorphism from the consensus sequence and is now different from that assigned by us previously (Anisimov et al , 2007). We found that two of the altaica strains (I-3455 and I-2359) possessed the same type A allele as did the previously sequenced Angola strain, but this subspecies also possessed LcrV of two other types, D (I-2131, I-3519) and E (I-3088, I-3132).…”

Section: Discussioncontrasting

confidence: 95%

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Amino acid and structural variability of Yersinia pestis LcrV protein

Anisimov

Dentovskaya

Panfertsev

et al. 2010

Infection, Genetics and Evolution

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The LcrV protein is a multifunctional virulence factor and protective antigen of the plague bacterium and is generally conserved between the epidemic strains of Yersinia pestis. We investigated the diversity in the LcrV sequences among non-epidemic Y. pestis strains which have a limited virulence in selected animal models and for humans. Sequencing of lcrV genes from 19 Y. pestis strains belonging to different phylogenetic groups (“subspecies”) showed that the LcrV proteins possess four major variable hotspots at positions 18, 72, 273, and 324–326. These major variations, together with other minor substitutions in amino acid sequences, allowed us to classify the LcrV alleles into five sequence types (A-E). We observed that the strains of different Y. pestis “subspecies” can have the same type of LcrV, including that conserved in epidemic strains, and different types of LcrV can exist within the same natural plague focus. Therefore, the phenomenon of “selective virulence” characteristic of the strains of the microtus biovar is unlikely to be the result of polymorphism of the V antigen. The LcrV polymorphisms were structurally analyzed by comparing the modeled structures of LcrV from all available strains. All changes except one occurred either in flexible regions or on the surface of the protein, but local chemical properties (i.e. those of a hydrophobic, hydrophilic, amphipathic, or charged nature) were conserved across all of the strains. Polymorphisms in flexible and surface regions are likely subject to less selective pressure, and have a limited impact on the structure. In contrast, the substitution of tryptophan at position 113 with either glutamic acid or glycine likely has a serious influence on the regional structure of the protein, and these mutations might have an effect on the function of LcrV. The polymorphisms at positions 18, 72 and 273 were accountable for differences in the oligomerization of LcrV.

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Section: Discussioncontrasting

confidence: 95%

“… (A part of this work was presented at the 9 th International Symposium on Yersinia , October 10–14, 2006, in Lexington, Kentucky, USA) (Anisimov et al , 2007). …”

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confidence: 99%

Amino acid and structural variability of Yersinia pestis LcrV protein

Anisimov

Dentovskaya

Panfertsev

et al. 2010

Infection, Genetics and Evolution

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“…Further, F1 capsular antigen is dispensable for virulence (59,60) and the LcrV amino acid sequence has diverged among Y. pestis strains (1, 61). Therefore, the F1-V-based subunit vaccines most likely will not provide optimal protection across all plague-causing strains in humans, specifically those that have been intentionally modified for possible use in terrorist attacks (62,63). The live-attenuated vaccines that promote humoral and cellmediated immune responses may represent a better option for overcoming the above-mentioned shortcomings of the subunit vaccines (9,12).…”

Section: Discussionmentioning

confidence: 99%

Intramuscular Immunization of Mice with a Live-Attenuated Triple Mutant of Yersinia pestis CO92 Induces Robust Humoral and Cell-Mediated Immunity To Completely Protect Animals against Pneumonic Plague

Tiner

Sha

Ponnusamy

et al. 2015

Clin. Vaccine Immunol.

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Y ersinia pestis is the causative agent of plague (1), and there has been a rise in the number of plague cases globally in recent years possibly due to climate changes and shifting of the rodent carrier range (2). The organism is classified as a tier 1 select agent (3-5), and the progression of septicemic and pneumonic forms of plague is very rapidly fatal after the first appearance of symptoms (4, 6-8). Alarmingly, antibiotic-resistant strains of Y. pestis have been isolated from plague patients and also have been engineered for bioweaponization (4). Therefore, vaccination is the optimal strategy for human protection against this deadly disease; however, there are currently no Food and Drug Administration (FDA)-licensed plague vaccines available in the United States (9-11).Although a heat-killed plague vaccine composed of the Y. pestis 195/P strain was in use in the United States until 1999, the production of this vaccine was discontinued because of its effectiveness only against the bubonic plague and not the pneumonic form and also because it was highly reactogenic in humans (12, 13). Various live-attenuated Y. pestis EV76 vaccine strains, which lack the pigmentation locus (pgm) required for iron acquisition, provide protection against bubonic and pneumonic plague and are being used in some parts of the world where plague is endemic (9). However, these EV76-based vaccines are not genetically uniform and are also highly reactogenic (14); hence, they do not meet the standards for FDA approval. In addition, the ⌬pgm mutants of Y. pestis (e.g., the KIM/D27 strain) may not be safe because of a reported case of fatal infection in an individual with hemochromatosis (15,16).In an effort to search for a new live-attenuated plague vaccine, we recently constructed a ⌬lpp ⌬msbB ⌬ail triple mutant, with deleted genes encoding Braun lipoprotein (Lpp), an acetyltransferase (MsbB), and the attachment invasion locus (Ail) (17). Lpp

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“…Nevertheless, enzootic strains are attenuated in many mammalian species, including guinea pigs and primates, but virulent in the rodent Superfamily Muroidea (Anisimov et al, 2004). Although pestoides isolates possess polymorphism in LcrV (Anisimov et al, 2007), a major pCD/pYVencoded regulator, T3SS effector, and virulence factor, it seems unlikely that these differences influence biological activity (Abramov et al, 2007). The purposes of this report are to provide a description of ten typical enzootic isolates and to demonstrate that only three produce functional Zwf while, in stark contrast to epidemic isolates of Y. pestis, all express biologically active AspA.…”

Section: Introductionmentioning

confidence: 99%

Attenuated enzootic (pestoides) isolates of Yersinia pestis express active aspartase

et al. 2009

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It is established that Yersinia pestis, the causative agent of bubonic plague, recently evolved from enteropathogenic Yersinia pseudotuberculosis by undergoing chromosomal degeneration while acquiring two unique plasmids that facilitate tissue invasion (pPCP) and dissemination by fleabite (pMT). Thereafter, plague bacilli spread from central Asia to sylvatic foci throughout the world. These epidemic isolates exhibit a broad host range including man as opposed to enzootic (pestoides) variants that remain in ancient reservoirs where infection is limited to muroid rodents. Cells of Y. pseudotuberculosis are known to express glucose-6-phosphate dehydrogenase (Zwf) and aspartase (AspA); these activities are not detectable in epidemic Y. pestis due to missense mutations (substitution of proline for serine at amino position 155 of Zwf and leucine for valine at position 363 of AspA). In this study, functional Zwf was found in pestoides strains E, F and G but not seven other enzootic isolates; enzymic activity was associated with retention of serine at amino acid position 155. Essentially, full AspA activity occurred in pestoides isolates where valine (pestoides A, B, C and D) or serine (pestoides E, F, G and I) occupied position 363. Reduced activity occurred in strains Angola and A16, which contained phenylalanine at this position. The k cat but not K m of purified AspA from strain Angola was significantly reduced. In this context, aspA of the recently described attenuated enzootic microtus biovar encodes active valine at position 363, further indicating that functional AspA is a biomarker for avirulence of Y. pestis in man.

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Variability of the Protein Sequences of LcrV Between Epidemic and Atypical Rhamnose-Positive Strains of Yersinia pestis

Cited by 10 publications

References 14 publications

Amino acid and structural variability of Yersinia pestis LcrV protein

Amino acid and structural variability of Yersinia pestis LcrV protein

Intramuscular Immunization of Mice with a Live-Attenuated Triple Mutant of Yersinia pestis CO92 Induces Robust Humoral and Cell-Mediated Immunity To Completely Protect Animals against Pneumonic Plague

Attenuated enzootic (pestoides) isolates of Yersinia pestis express active aspartase

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