Dave Wagner | Novel Antimicrobial Resistant Strain of Yersinia Pestis
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Associate Director of PMI
Dave Wagner
Wagner is a disease ecologist whose primary research interests are the ecology and evolution of infectious diseases. He uses genetic and genomic variation within pathogen, vector and host species to better understand the distribution, ecology, evolutionary history, and transmission patterns of infectious diseases. Wagner, who has published more than 140 articles in scholarly journals, is one of the world’s leading experts on several pathogens and infectious diseases, including plague and tularemia.
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Abstract
Transmission of antimicrobial resistant Yersinia pestis during a pneumonic plague outbreak
Pneumonic plague (PP), caused by Yersinia pestis, is the most feared clinical form of plague due to its rapid lethality and potential to cause outbreaks. PP outbreaks are now rare due to antimicrobial therapy.
A PP outbreak in Madagascar involving transmission of a Y. pestis strain resistant to streptomycin, the current recommended first-line treatment in Madagascar, was retrospectively characterized using epidemiology, clinical diagnostics, molecular characterization, and animal studies.
The outbreak occurred in February 2013 in the Faratsiho district of Madagascar and involved 22 cases, including three untreated fatalities. The 19 other cases participated in funeral practices for the fatal cases and fully recovered after combination antimicrobial therapy: intramuscular streptomycin followed by oral co-trimoxazole. The Y. pestis strain that circulated during this outbreak is resistant to streptomycin resulting from a spontaneous point mutation in the 30S ribosomal protein S12 (rpsL) gene. This same mutation causes streptomycin resistance in two unrelated Y. pestis strains, one isolated from a fatal PP case in a different region of Madagascar in 1987 and another isolated from a fatal PP case in China in 1996, documenting this mutation has occurred independently at least three times in Y. pestis. Laboratory experiments revealed this mutation has no detectable impact on fitness or virulence, and revertants to wild-type are rare in other species containing it, suggesting Y. pestis strains containing it could persist in the environment.
Unique AMR strains of Y. pestis continue to arise in Madagascar and can be transmitted during PP outbreaks.
Figures
Figure 1.
A) Map of commune of Faratsiho indicating locations associated with this PP outbreak; location 3 is shown on panel B as it is located outside of this commune.
B) Map of Madagascar indicating the five different districts from which AMR/MDR strains of Y. pestis have been isolated, year and host of isolation, resistance phenotype (STR, streptomycin; DOX, doxycycline), and mechanism of resistance for each AMR/MDR strain. Faratsiho District is shaded red and, within it, the commune of Faratsiho is shaded gray; the latter corresponds to panel A.
Figure 2.
Outbreak transmission.
A) Timeline of events associated with this PP outbreak.
B) Case interactions during wakes as well as information on case-characteristics (age and gender).
Figure 3.
Maximum likelihood phylogeny for 38 Y. pestis isolates from Madagascar created using 387 core genome SNPs discovered from WGSs and rooted using North American strain CO92 (CO92 branch not shown). Labels for each isolate indicate identification number, year of isolation, host, and district of isolation; letters on branches indicate previously identified lineages [25]. Two isolates obtained from this PP outbreak in Faratsiho District, 56/13 and 59/13, are identical at all examined SNPs and share the rpsL SNP 215,373, which confers resistance to streptomycin. The rpsL SNP 215,373 is additionally found on the branch leading to isolate 12/87, which is also resistant to streptomycin; SNP 215,373 is the only homoplastic SNP in this phylogeny.
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NAU Press Release
Let’s get the word out for Dave Wagner’s important research on the Transmission of antimicrobial resistant Yersinia pestis during a pneumonic plague outbreak.
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