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      Multiple Antimicrobial Resistance in Plague: An Emerging Public Health Risk

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          Abstract

          Antimicrobial resistance in Yersinia pestis is rare, yet constitutes a significant international public health and biodefense threat. In 1995, the first multidrug resistant (MDR) isolate of Y. pestis (strain IP275) was identified, and was shown to contain a self-transmissible plasmid (pIP1202) that conferred resistance to many of the antimicrobials recommended for plague treatment and prophylaxis. Comparative analysis of the DNA sequence of Y. pestis plasmid pIP1202 revealed a near identical IncA/C plasmid backbone that is shared by MDR plasmids isolated from Salmonella enterica serotype Newport SL254 and the fish pathogen Yersinia ruckeri YR71. The high degree of sequence identity and gene synteny between the plasmid backbones suggests recent acquisition of these plasmids from a common ancestor. In addition, the Y. pestis pIP1202-like plasmid backbone was detected in numerous MDR enterobacterial pathogens isolated from retail meat samples collected between 2002 and 2005 in the United States. Plasmid-positive strains were isolated from beef, chicken, turkey and pork, and were found in samples from the following states: California, Colorado, Connecticut, Georgia, Maryland, Minnesota, New Mexico, New York and Oregon. Our studies reveal that this common plasmid backbone is broadly disseminated among MDR zoonotic pathogens associated with agriculture. This reservoir of mobile resistance determinants has the potential to disseminate to Y. pestis and other human and zoonotic bacterial pathogens and therefore represents a significant public health concern.

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          Most cited references 18

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          Complete genome sequence of a multiple drug resistant Salmonella enterica serovar Typhi CT18.

          Salmonella enterica serovar Typhi (S. typhi) is the aetiological agent of typhoid fever, a serious invasive bacterial disease of humans with an annual global burden of approximately 16 million cases, leading to 600,000 fatalities. Many S. enterica serovars actively invade the mucosal surface of the intestine but are normally contained in healthy individuals by the local immune defence mechanisms. However, S. typhi has evolved the ability to spread to the deeper tissues of humans, including liver, spleen and bone marrow. Here we have sequenced the 4,809,037-base pair (bp) genome of a S. typhi (CT18) that is resistant to multiple drugs, revealing the presence of hundreds of insertions and deletions compared with the Escherichia coli genome, ranging in size from single genes to large islands. Notably, the genome sequence identifies over two hundred pseudogenes, several corresponding to genes that are known to contribute to virulence in Salmonella typhimurium. This genetic degradation may contribute to the human-restricted host range for S. typhi. CT18 harbours a 218,150-bp multiple-drug-resistance incH1 plasmid (pHCM1), and a 106,516-bp cryptic plasmid (pHCM2), which shows recent common ancestry with a virulence plasmid of Yersinia pestis.
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            Yersinia pestis--etiologic agent of plague.

            Plague is a widespread zoonotic disease that is caused by Yersinia pestis and has had devastating effects on the human population throughout history. Disappearance of the disease is unlikely due to the wide range of mammalian hosts and their attendant fleas. The flea/rodent life cycle of Y. pestis, a gram-negative obligate pathogen, exposes it to very different environmental conditions and has resulted in some novel traits facilitating transmission and infection. Studies characterizing virulence determinants of Y. pestis have identified novel mechanisms for overcoming host defenses. Regulatory systems controlling the expression of some of these virulence factors have proven quite complex. These areas of research have provide new insights into the host-parasite relationship. This review will update our present understanding of the history, etiology, epidemiology, clinical aspects, and public health issues of plague.
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              Plague as a biological weapon: medical and public health management. Working Group on Civilian Biodefense.

              The Working Group on Civilian Biodefense has developed consensus-based recommendations for measures to be taken by medical and public health professionals following the use of plague as a biological weapon against a civilian population. The working group included 25 representatives from major academic medical centers and research, government, military, public health, and emergency management institutions and agencies. MEDLINE databases were searched from January 1966 to June 1998 for the Medical Subject Headings plague, Yersinia pestis, biological weapon, biological terrorism, biological warfare, and biowarfare. Review of the bibliographies of the references identified by this search led to subsequent identification of relevant references published prior to 1966. In addition, participants identified other unpublished references and sources. Additional MEDLINE searches were conducted through January 2000. The first draft of the consensus statement was a synthesis of information obtained in the formal evidence-gathering process. The working group was convened to review drafts of the document in October 1998 and May 1999. The final statement incorporates all relevant evidence obtained by the literature search in conjunction with final consensus recommendations supported by all working group members. An aerosolized plague weapon could cause fever, cough, chest pain, and hemoptysis with signs consistent with severe pneumonia 1 to 6 days after exposure. Rapid evolution of disease would occur in the 2 to 4 days after symptom onset and would lead to septic shock with high mortality without early treatment. Early treatment and prophylaxis with streptomycin or gentamicin or the tetracycline or fluoroquinolone classes of antimicrobials would be advised.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                PLoS ONE
                plos
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2007
                21 March 2007
                : 2
                : 3
                Affiliations
                [1 ]National Center for Cool and Cold Water Aquaculture, Agricultural Research Service, United States Department of Agriculture (USDA), Kearneysville, West Virginia, United States of America
                [2 ]The Institute for Genomic Research, Rockville, Maryland, United States of America
                [3 ]Office of Research, Center for Veterinary Medicine-Food and Drug Administration (CVM-FDA), Laurel, Maryland, United States of America
                [4 ]Institut Pasteur, Yersinia Research Unit, Paris, France
                [5 ]University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, United States of America
                [6 ]Office of Applied Research and Safety Assessment, Center for Food Safety and Applied Nutrition-Food and Drug Administration (CFSAN-FDA), Laurel, Maryland, United States of America
                [7 ]Northern Arizona University, Flagstaff, Arizona, United States of America
                [8 ]Institut Pasteur, Antananarivo, Madagascar
                [9 ]Department of Zoology, North Carolina State University, Fletcher, North Carolina, United States of America
                [10 ]Public Health Laboratory Services, DoD-GEIS, Silver Spring, Maryland, United States of America
                Baylor College of Medicine, United States of America
                Author notes
                * To whom correspondence should be addressed. E-mail: jravel@ 123456tigr.org

                Conceived and designed the experiments: JR TW. Performed the experiments: JR EC TW WF PM DW MR. Analyzed the data: JR MR DR TW WF ME PM DW. Contributed reagents/materials/analysis tools: JR EC LR DW TW PM DW MM JL TC MR LL JH. Wrote the paper: JR TW WF. Other: Edited Manuscript: EC TC DW PM.

                Article
                07-PONE-RA-00761
                10.1371/journal.pone.0000309
                1819562
                17375195
                This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
                Page count
                Pages: 6
                Categories
                Research Article
                Genetics and Genomics/Microbial Evolution and Genomics
                Microbiology/Applied Microbiology
                Infectious Diseases/Antimicrobials and Drug Resistance
                Public Health and Epidemiology/Infectious Diseases
                Genetics and Genomics/Microbial Evolution and Genomics
                Infectious Diseases/Antimicrobials and Drug Resistance
                Microbiology/Applied Microbiology
                Public Health and Epidemiology/Infectious Diseases

                Uncategorized

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