no evidence of plasmid-mediated antibiotic resistance in north american yersinia pestis
DESCRIPTION
No evidence of plasmid-mediated antibiotic resistance in North American Yersinia pestis. David M. Wagner 1 , Janelle Runberg 1 , Amy J. Vogler 1 , Judy Lee 1 , Lance B. Price 2 , David M. Engelthaler 2 , Jacques Ravel 3 , & Paul Keim 1 - PowerPoint PPT PresentationTRANSCRIPT
David M. Wagner1, Janelle Runberg1, Amy J. Vogler1, Judy Lee1, Lance B. Price2, David M. Engelthaler2,
Jacques Ravel3, & Paul Keim1
1Northern Arizona University, Flagstaff, AZ;
2Translational Genomics Research Institute (TGen), Flagstaff, AZ; 3University of Maryland School of
Medicine, Baltimore, MD
No evidence of plasmid-mediated antibiotic resistance
in North American Yersinia pestis
Plague Transmission Cycle
Pathways
usual
occasionalrare or
theoreticalCommensal Rat Cycle
InfectiveFlea
InfectiveFlea
DomesticRodent
DomesticRodent
Dire
ct
co
nta
ct
WildRodent
WildRodent
InfectiveFlea
InfectiveFlea
Direct contact
Wild Rodent Cycle
Bubonicor Septicemic
plague
Secondaryplague
pneumonia
Dir
ec
t c
on
tac
t
co
nta
min
ate
d s
oil
Primarypneumonic
plaguecases
Slide courtesy of Ken Gage
Three Plague Pandemics – 200 Million Deaths
Perry & Fetherston 1997Achtman et al. 1999
Control of Plague – Hygiene & Antibiotics
Kill or eliminate habitat for rat hosts – very important in urban areas
Control flea vectors using insecticidesRapid diagnosis, followed byStandard treatment with antibiotics
Streptomycin Tetracyclines Sulfonamides
Plague Today – Global Distribution
Stenseth et al. 2008. PLoS Medicine
Plague Today – Increases in Africa
Stenseth et al. 2008. PLoS Medicine
Plague Today – Increases in Africa
Stenseth et al. 2008. PLoS Medicine
Plague Vaccines – Little Success to Date
Killed vaccine no longer available in the USLive attenuated vaccine not licensed for humansInjected subunit vaccines show promise for futureAs a result, efforts to save human lives are
still focused on rapid diagnosis followed by treatment with antibiotics
Resistance to antibiotics could represent a serious threat to human health given high pathogenicity and ability to rapidly spread under optimal conditions
Antimicrobial Resistance in Y. pestis
Strain 17/95 16/95
Streptomycin Resistance
YES YES
Tetracycline Resistance
YES NO
Sulfonamide Resistance
YES NO
Other Resistance YES NO
Country of Origin Madagascar Madagascar
Year of Isolation 1995 1995
Resistance Plasmid pIP1202 pIP1203
Galimand et al. 1997. New England Journal of Medicine
Typical and Atypical Plasmids in Y. pestis
Three main plasmids, all associated w/ virulence: pCD1 (found in all pathogenic Yersinia) pPCP1 pMT1
pMT1 very similar to plasmid in Salmonella enterica Serovar Typhi
Several different studies have documented atypical plasmids present in Y. pestis strains
Indicates that this species readily acquires plasmids
Filippov et al. 1990; Parkhill et al. 2001 ; Prentice et al. 2001
Plasmid Acquisition Likely Occurs in Fleas
In co-infected fleas, E. coli donated pIP1202 to Y. pestis at frequency of 10-3 after three days
After four weeks, 95% of co-infected fleas contained MDR Y. pestis (Hinnebusch et al. 2002)
Y. pestis infected fleas can harbor diverse bacterial communities (Wagner et al. unpubl.)
Y. pestis infected fleas commonly co-infected with Salmonella spp. (Eskey et al. 1951)
What do we know about MDR plasmids in Y. pestis?
Plasmid pIP1202 from Y. pestis
•Similar to MDR plasmids from Y. ruckeri and S. enterica Newport
•All share the same plasmid backbone (IncA/C)
•Backbone contains gene conferring resistance to sulfonamides (sul2)
•Other resistance genes vary
Welch et al. 2007. PLoS One
Similar MDR Plasmids in US Meat Products
Plasmids with similar IncA/C backbones and varying MDR profiles found in bacteria recovered from meat
Sources: turkey, chicken, beef, porkStates: CA, CO, CT, GA, IA, MD, MN, ND, NM, NY,
TN, and ORHosts: S. enterica Typhimurium, Newport, Kentucky,
Heidelberg, Dublin, Bredeney, Klebsiella spp., E. coliMost resistant to tetracycline and many resistant to
streptomycin and others, in addition to sulfonamidesMany strains readily transferred plasmids to Y.
ruckeri
Welch et al. 2007. PLoS One
No Evidence in North American Y. pestis
State N Years
Arizona 151 1975, 1977-1984, 1986-1989, 1992-1996, 1998, 2000-2002
California 129 1943, 1962, 1970, 1977, 1979-1980, 1983-1999
Colorado 97 1963, 1968, 1989, 1992, 1995-1997, 1999-2002
Idaho 2 1987, 1997
Kansas 17 1997, 1999
Montana 11 1987, 1992-1993
North Dakota 2 1986, 1993
New Mexico 124 1950, 1976-1977, 1979-1988, 1991-1992, 1994-1995, 1997-2002
Nevada 36 1980-1985, 1987, 1992-1995
Oregon 18 1959, 1970-1971, 1977, 1979, 1981-1984, 1987
Texas 5 unknown
Utah 55 1965, 1981-1984, 1991-1995, 1999-2001
Washington 2 1984
Wyoming 64 1978, 1980, 1982-1983, 1985-1987, 1989-1990, 1997, 2000-2001
Discussion/Conclusions
No IncA/C plasmid-mediated MDR in North American Y. pestis – why?
Our isolates mostly from human plague investigations
MDR resistant plasmids in meats probably arose in Concentrated Animal Feeding Operations (CAFOs)
Plague limited to 17 westernmost states, whereas most CAFOs in the eastern states
Plausible that MDR Y. pestis could arise in fleas co-infected with MDR enteric pathogens and Y. pestis
However, no obvious selection pressure to maintain these MDR plasmids in Y. pestis
Acknowledgements
Funding: NIH-NIAID, NIH Pacific-Southwest Regional Center of Excellence, Arizona Game & Fish, NAU-Cowden Endowment
CDC-Ft. Collins: Ken Gage, Becky Eisen, Jeannine Petersen, Marty Schriefer, Michael Kosoy
Arizona Department of Health Services: Craig LevyCoconino County Health Department: Marlene
GaitherNAU Y. pestis Group: Amy Vogler, Becky Colman,
Joe Busch, Judy Lee, Adina Doyle, Roxanne Nera