Hotspots of genetic change in Yersinia pestis.

The relative contributions of mutation rate variation, selection, and recombination in shaping genomic variation in bacterial populations remain poorly understood. Here we analyze 3318 Yersinia pestis genomes, spanning nearly a century and including 2336 newly sequenced strains, to shed light on the patterns of genetic diversity and variation distribution at the population level. We identify 45 genomic regions ("hot regions", HRs) that, although comprising a minor fraction of the genome, are hotbeds of genetic variation.

A novel sORF gene mutant strain of Yersinia pestis vaccine EV76 offers enhanced safety and improved protection against plague.

We recently identified two virulence-associated small open reading frames (sORF) of Yersinia pestis, named yp1 and yp2, and null mutants of each individual genes were highly attenuated in virulence. Plague vaccine strain EV76 is known for strong reactogenicity, making it not suitable for use in humans. To improve the immune safety of EV76, three mutant strains of EV76, Δyp1, Δyp2, and Δyp1&yp2 were constructed and their virulence attenuation, immunogenicity, and protective efficacy in mice were evaluated.

Interplays of mutations in , , and contribute to phage resistance in .

Plague caused by remains a public health threat worldwide. Because multidrug-resistant strains have been found in both humans and animals, phage therapy has attracted increasing attention as an alternative strategy against plague. However, phage resistance is a potential drawback of phage therapies, and the mechanism of phage resistance in is yet to be investigated.

A novel mechanism of streptomycin resistance in Yersinia pestis: Mutation in the rpsL gene.

Streptomycin is considered to be one of the effective antibiotics for the treatment of plague. In order to investigate the streptomycin resistance of Y. pestis in China, we evaluated streptomycin susceptibility of 536 Y.

Human Macrophages Clear the Biovar Microtus Strain of More Efficiently Than Murine Macrophages.

is the etiological agent of the notorious plague that has claimed millions of deaths in history. Of the four known biovars (Antiqua, Medievalis, Orientalis, and Microtus), Microtus strains are unique for being highly virulent in mice but avirulent in humans. Here, human peripheral lymphocytes were infected with the fully virulent 141 strain or the Microtus strain 201, and their transcriptomes were determined and compared.

Serological Epidemiological Investigation of Tibetan Sheep (Ovis aries) Plague in Qinghai, China.

The plague, which is caused by the Gram-negative coccobacillus bacterium Yersinia pestis, has been classified as a reemerging infectious disease by the World Health Organization. The Qinghai-Tibet Plateau natural plague focus is the largest plague focus in China, and Marmota himalayana is the primary host of the plague. Tibetan sheep (Ovis aries) were first identified as naturally infected hosts of Y.

Genetic diversity and spatial-temporal distribution of Yersinia pestis in Qinghai Plateau, China.

Background: Plague, caused by the bacterium Yersinia pestis, is a highly infectious, zoonotic disease. Hundreds of human plague cases are reported across the world annually. Qinghai Plateau is one of the most severely affected plague regions in China, with more than 240 fatal cases of Y.

Shiga Toxin-Producing Escherichia coli in Plateau Pika (Ochotona curzoniae) on the Qinghai-Tibetan Plateau, China.

Shiga toxin-producing Escherichia coli (STEC) are an emerging group of zoonotic pathogens. Ruminants are the natural reservoir of STEC. In this study we determined the prevalence and characteristics of the STEC in plateau pika (Ochotona curzoniae) on the Qinghai-Tibetan Plateau, China.

[The epidemiology and etiology research of Tibetan sheep plague in Qinghai plateau].

Objective: To identify the epidemiology and etiology characteristics of Tibetan sheep plague in Qinghai plateau.

Methods: The background materials of Qinghai Tibetan sheep plague found during 1975 to 2009 were summarized, the regional, time and interpersonal distribution, infection routes, ecological factors for the spread were used to analyze; followed by choosing 14 Yersinia pestis strains isolated from such sheep for biochemical test, toxicity test, virulence factors identification, plasmid analysis, and DFR genotype.

Results: From 1975 to 2009, 14 Yersinia pestis strains were isolated from Tibetan sheep in Qinghai province.

[Study of the plasmid profiles and geographical distribution of Yersinia pestis in China].

Objective: To analyze the plasmid features and geographical distribution characteristics of Yersinia pestis of different plague foci in China.

Methods: A total of 2 213 Yersinia pestis strains were colected from 11 Chinese plague foci separated during 1943 to 2012, and plasmid DNA according to alkali cracking method, and measured the relative molecular mass (Mr) of plasmid DNA based on the standard plasmid contrast method, then analyzed the plasmid profiles by agar gel electrophoresis.

Results: A total of 2 213 strains had 16 kinds of plasmids with different Mr, including 4×10(6), 6×10(6), 7×10(6), 13×10(6), 16×10(6), 20×10(6), 22×10(6), 23×10(6), 27×10(6), 30×10(6), 36×10(6), 45×10(6), 52×10(6), 65×10(6), 72×10(6) and 90×10(6).

Prevalence and characteristics of Shiga toxin-producing Escherichia coli isolated from retail raw meats in China.

Shiga toxin-producing Escherichia coli (STEC) causes diarrhea, hemorrhagic colitis, and hemolytic uremic syndrome in humans. Most human infections are attributed to consumption of STEC-contaminated foodstuffs of animal origin. In this study, we evaluated the prevalence of STEC from retail raw meats collected from two geographical regions in China.

Comparison of virulence between the Yersinia pestis Microtus 201, an avirulent strain to humans, and the vaccine strain EV in rhesus macaques, Macaca mulatta.

Our previous study has demonstrated that Yersinia pestis Microtus 201 is a low virulent strain to the Chinese-origin rhesus macaques, Macaca mulatta, and can protect it against high dose of virulent Y. pestis challenge by subcutaneous route. To investigate whether the Y.

[Regional genotyping and the geographical distribution regarding Yersinia pestis isolates in China].

Objective: To type Yersinia (Y.) pestis isolates under different regions (DFR) and to observe their geographical distributions in China.

Methods: 23 DFRs primers and PMT1 (plasmid) primer were used to verify the DFR genomovars of Y.

[Sources of infection on human plague in Qinghai province].

Objective: To study the biological and genetic characteristics of 119 strains of Yersinia (Y.) pestis isolated from plague patients in Qinghai province, from 1958-2012.

Methods: Both regular methods and different region(DFR)molecular typing techniques were used to study the epidemiological characteristics on 119 strains of Y.

Yersinia pestis biovar Microtus strain 201, an avirulent strain to humans, provides protection against bubonic plague in rhesus macaques.

Yersinia pestis biovar Microtus is considered to be a virulent to larger mammals, including guinea pigs, rabbits and humans. It may be used as live attenuated plague vaccine candidates in terms of its low virulence. However, the Microtus strain's protection against plague has yet to be demonstrated in larger mammals.

Shiga toxin-producing Escherichia coli in yaks (Bos grunniens) from the Qinghai-Tibetan Plateau, China.

Shiga toxin (Stx)-producing Escherichia coli (STEC) are recognized as important human pathogens of public health concern. Many animals are the sources of STEC. In this study we determined the occurrence and characteristics of the STEC in yaks (Bos grunniens) from the Qinghai-Tibetan plateau, China.

A live attenuated strain of Yersinia pestis ΔyscB provides protection against bubonic and pneumonic plagues in mouse model.

To develop a safe and effective live plague vaccine, the ΔyscB mutant was constructed based on Yersinia pestis biovar Microtus strain 201 that is avirulent to humans, but virulent to mice. The virulence, immunogenicity and protective efficacy of the ΔyscB mutant were evaluated in this study. The results showed that the ΔyscB mutant was severely attenuated, elicited a higher F1-specific antibody titer and provided protective efficacy against bubonic and pneumonic plague in mouse model.

Acquisition of maternal antibodies both from the placenta and by lactation protects mouse offspring from Yersinia pestis challenge.

Artificially passive immunization has been demonstrated to be effective against Yersinia pestis infection in animals. However, maternal antibodies' protective efficacy against plague has not yet been demonstrated. Here, we evaluated the kinetics, protective efficacy, and transmission modes of maternal antibodies, using mice immunized with plague subunit vaccine SV1 (20 μg of F1 and 10 μg of rV270).

Histopathological observation of immunized rhesus macaques with plague vaccines after subcutaneous infection of Yersinia pestis.

In our previous study, complete protection was observed in Chinese-origin rhesus macaques immunized with SV1 (20 µg F1 and 10 µg rV270) and SV2 (200 µg F1 and 100 µg rV270) subunit vaccines and with EV76 live attenuated vaccine against subcutaneous challenge with 6×10(6) CFU of Y. pestis. In the present study, we investigated whether the vaccines can effectively protect immunized animals from any pathologic changes using histological and immunohistochemical techniques.

[Evaluation of immunization protection efficacy of plague subunit vaccine].

Objective: To evaluate the protective efficacy of plague subunit vaccine, BALB/c mice, guinea pigs and rabbits were used in this study.

Methods: Groups of mice (10 per group), guinea pigs (14 per group) and rabbits (6 per group) were immunized with F1 + rV270 vaccine, EV76 vaccine and alum adjuvant by intramuscular route, respectively. Serum antibody titres of mice, guinea pigs and rabbits were determined by ELISA and the immunized animals were challenged with 10(6) CFU of Y.