Original Article
Brief Report
Multidrug Resistance in Yersinia pestis Mediated by a Transferable Plasmid
N Engl J Med 1997; 337:677-681September 4, 1997
- Article
Yersinia pestis is the causative agent of plague, a zoonotic disease transmitted to humans through flea bites and typically characterized by the appearance of a tender and swollen lymph node, the bubo. Human-to-human transmission can occur, through either the bite of fleas (bubonic plague) or respiratory droplets, causing an overwhelming infection called pneumonic plague.
The last plague pandemic began in Hong Kong in 1894 and spread throughout the world, establishing many endemic foci. Antibiotics and enforcement of public health measures significantly decreased the morbidity and mortality associated with the disease but did not allow its eradication. In fact, plague is now considered a reemerging disease1 for at least three reasons. First, there has been an increase in the number of cases reported to the World Health Organization.2 Second, plague reappeared in 1994 in an epidemic form in countries, including Malawi, Mozambique, and India, where it had been silent for 15 to 30 years. Third, the number of foci is gradually expanding in certain countries. In the United States for instance, the number of states reporting cases of human plague increased from 3 in the 1950s to 13 in the 1990s.3
Streptomycin, chloramphenicol, and tetracycline are used to treat plague, and tetracycline and sulfonamides are recommended for prophylaxis.4 Classically, Y. pestis isolates are uniformly susceptible to the antibiotics active against gram-negative bacteria.5-7
We report high-level resistance to multiple antibiotics, including all the drugs recommended for plague prophylaxis and therapy, in a clinical isolate of Y. pestis. The resistance genes were carried by a plasmid that could conjugate to other Y. pestis isolates. This report should serve as a warning of the risk of the spread of resistance in Y. pestis, a species previously considered universally susceptible to antibiotics.
Methods
Patient and Strains
The properties of the strains used are listed in Table 1Table 1
Properties of the Bacterial Strains Studied.. Y. pestis 17/95 biotype orientalis was isolated in 1995 in the Ambalavao district of Madagascar from a 16-year-old boy.5 The patient presented with fever, chills, and myalgia suggestive of malaria and was treated with quinine. Three days later, the appearance of a right inguinal bubo with high-grade fever (temperature, 41°C), delirium, and prostration led to the diagnosis of plague. The bubo was punctured, and the patient was treated with twice-daily intramuscular injections of streptomycin (2 g per day for 4 days) and oral trimethoprim–sulfamethoxazole (2 g per day for 10 days). The patient recovered but had severe asthenia for more than a month.Mediums and Resistance Studies
Brain–heart infusion broth and agar (Difco) were used. The minimal inhibitory concentrations of antibiotics were determined on Mueller–Hinton agar (Sanofi Diagnostics Pasteur). The cultures were incubated for 48 hours at 28°C for Y. pestis and for 18 hours at 37°C for Escherichia coli. Chloramphenicol acetyltransferase and aminoglycoside-modifying enzymes were assayed in supernatants (centrifuged at 100,000×g) after ultrasonic disintegration.12,13 Matting on filters was performed as described previously.14
Nucleic-Acid Techniques
Isolation of plasmid DNA, cleavage of restriction fragments, and purification of DNA fragments from agarose type VII (Sigma Chemical) were performed as described elsewhere.9 Purified DNA fragments to be used as probes were labeled with [α-32P]deoxycytidine triphosphate by nick translation. Hybridization was carried out under highly stringent conditions.9 The polymerase chain reaction (PCR) was performed on a DNA thermal cycler (model 2400, Perkin-Elmer Cetus). Double-stranded DNA sequencing was performed by the dideoxynucleotide chain-termination method15 with a modified T7 DNA polymerase and [α-35S]deoxyadenosine triphosphate.
Results
Antibiotic Resistance of Y. pestis 17/95
Disk-agar diffusion tests showed that Y. pestis 17/95 was resistant to ampicillin, chloramphenicol, kanamycin, streptomycin, spectinomycin, sulfonamides, tetracycline, and minocycline. Resistance to ampicillin was due to the production of a beta-lactamase, and resistance to chloramphenicol was due to the production of a chloramphenicol acetyltransferase. Resistance to kanamycin was due to synthesis of a type I 3'-aminoglycoside phosphotransferase. The strain was also resistant to high levels of streptomycin–spectinomycin as a result of the production of 3
-9-aminoglycoside adenylyltransferase. Y. pestis 17/95 was resistant to sulfonamides6 but remained susceptible to trimethoprim (Table 2Table 2
Minimal Inhibitory Concentrations of Various Antibiotics against the Bacterial Strains Studied.), and no synergism was detected between the two drugs by the checkerboard method.16 A small percentage of Y. pestis 17/95 spontaneously lost the resistance determinants en bloc (1 of 100 colonies tested after 10 days of incubation in the absence of antibiotics), and this clone, 17/95-I, was studied further.
All the resistance genes were transferred by conjugation from Y. pestis 17/95 to avirulent Y. pestis 6/69cN at a frequency of 1.5×10-2 per donor colony-forming unit. Selection for transfer of one of these resistance characters revealed the transfer of all six. The minimal inhibitory concentrations of antibiotics for the parent strain, the clone that had lost the resistance determinants, strain 6/69cN, and a strain obtained by the conjugation of 17/95 with 6/69cN are shown in Table 2.
Plasmid DNA from Y. pestis 6/69, 17/95, and 17/95-I was extracted and digested with EcoRV (Figure 1AFigure 1
Analysis of Plasmid DNA by Agarose-Gel Electrophoresis (Panel A) and Hybridization (Panel B)., lanes 1, 2, and 3). Comparison of the restriction profiles indicated that strain 17/95 contained fragments corresponding to an additional plasmid, designated pIP1202, of approximately 150,000 bp, as estimated by pulsed-field gel electrophoresis (data not shown).Characterization of Plasmid pIP1202
Plasmid pIP1202 was transferred by conjugation from Y. pestis 17/95 to E. coli K802N and RR1 at frequencies of approximately 1 ×10-2. The minimal inhibitory concentrations of antibiotics for E. coli K802N and strain BM4354, obtained by conjugation of Y. pestis 17/95 with E. coli K802N, are shown in Table 2. The retransfer of pIP1202 from E. coli BM4359 to Y. pestis 6/69cN and E. coli K802N occurred at frequencies of 1.1 × 10-4 and 5.7 × 10-5, respectively.
Approximately 5 percent of E. coli BM4354 did not contain plasmid pIP1202. Approximately 1 percent had lost part of the resistant determinants, generating plasmids pIP1202-1, -2, -3, and -4 (in Table 1), which were used to assess the incompatibility of the plasmids in experiments performed by reciprocal conjugation. Plasmid pIP1202-2 exhibited strong incompatibility with pIP55-1, which belongs to the Inc6-C group.17 Hybridization with a probe specific for Inc6-C replicons18 was detected only with plasmid DNA from the parental strain 17/95 and the E. coli strain that had acquired pIP1202 by conjugation from 17/95, confirming that this plasmid belongs to incompatibility group Inc6-C (data not shown).
Analysis of Plasmid DNA
Partial sequencing of an 864-bp PCR product obtained with oligodeoxynucleotides specific for bla TEM-1 indicated the presence of a cytosine at position 317 (numbering according to Sutcliffe19), confirming that resistance to ampicillin was due to the presence of the gene for TEM-1 penicillinase. The probe corresponding to catI hybridized to pIP1202 DNA, and the plasmid conferred to E. coli DB10 resistance to fusidic acid,20 indicating that resistance to chloramphenicol was due to the production of a type I chloramphenicol acetyltransferase. Probes internal to the aph(3')-I and aad(3
Discussion
Y. pestis is considered universally susceptible to antibiotics recommended and widely used for prophylaxis and treatment of plague.4 In recent studies the isolates tested were susceptible in vitro to all antibiotics active against gram-negative bacteria,6,7 with the exception of tetracycline in rare cases.22
Multidrug-resistant Y. pestis 17/95 was isolated in 1995 in the Ambalavao district of Madagascar from a patient who presented with symptoms of bubonic plague.5 Despite extensive surveillance of strains of Y. pestis isolated between 1926 and 1995 in Madagascar, no multidrug-resistant strain was detected.5,22 Strain 17/95 was resistant not only to all the antibiotics recommended for therapy (chloramphenicol, streptomycin, and tetracycline) and prophylaxis (sulfonamides and tetracycline) of plague4 but also to drugs that may represent alternatives to classic therapy, such as ampicillin, kanamycin, spectinomycin, and minocycline. The isolate remained susceptible to cephalosporins, other aminoglycosides, quinolones, and trimethoprim, and treatment with trimethoprim, despite its lack of synergism with sulfonamides, most likely led to the patient's recovery.
The resistance determinants were carried by the conjugative plasmid pIP1202. Several observations strongly argue for an origin of this plasmid in a member of the Enterobacteriaceae family. The resistance genes carried by pIP1202 were closely related in structure to plasmid-borne determinants commonly found in enterobacteria. The Inc6-C origin of replication of pIP1202 was typical of plasmids of this group of bacteria with a broad range of hosts, and the plasmid was easily transferred in vitro from E. coli to Y. pestis.
The site of the putative genetic transfer remains unknown. Enterobacteria are usually confined to the intestinal lumen of the host, whereas Y. pestis circulates in lymphatic vessels, the spleen, the liver, blood, and sometimes the lungs. However, intestinal enterobacteria and Y. pestis may come into contact when gut bacteria invade the bloodstream. Alternatively, if pIP1202 originated in an invasive pathogen, the contact between the two microorganisms may have occurred in the blood or in deep tissues. A third possibility is that intimate contact between Y. pestis and the donor was achieved outside the mammalian host, perhaps in the gut of a flea that ingested blood infected with both microorganisms.
The fact that the multidrug-resistant plasmid was highly transferable in vitro to other strains of Y. pestis, where it was stable, is of great concern. It is likely that this type of replicon can also be transferred among strains of Y. pestis in their natural environment and, therefore, that resistance may spread locally in this species. Even more alarming, the observation that Y. pestis is able to acquire, under natural conditions, a resistance plasmid, regardless of its true origin, indicates that such a clinically ominous event may occur again.
Supported in part by a grant from Actions Concertées du Réseau International des Instituts Pasteur et Instituts Associés and by the Madagascar Ministry of Health.
We are indebted to Carmen Buchrieser for performing the pulsed-field gel electrophoresis.
Source Information
From the National Reference Center for Antibiotics and the Unité des Agents Antibactériens (M.G., G.G., P.C.) and the National Reference Laboratory–World Health Organization Collaborating Center for Yersinia (A.G., E.C.), Institut Pasteur, Paris; and the Plague Central Laboratory, Institut Pasteur, Antananarivo, Madagascar (B.R., S.C.).
Address reprint requests to Dr. Carniel at the National Reference Laboratory–WHO Collaborating Center for Yersinia, Institut Pasteur, 28 rue du Dr. Roux, 75724 Paris CEDEX 15, France.
- References
References
1
Schrag SJ ,Wiener P . Emerging infectious disease: what are the relative roles of ecology and evolution? TREE 1995;10:319-324
Web of Science | Medline2
Human plague in 1994Wkly Epidemiol Rec 1996;71:165-168
Medline3
Human plague -- United States, 1993-1994
Medline4
Barnes AM, Quan TJ. Plague. In: Gorbach SL, Bartlett JG, Blacklow NR, eds. Infectious diseases. Philadelphia: W.B. Saunders, 1992:1285-91.
5
Rasoamanana B ,Leroy F ,Raharimanana C ,Chanteau S . Surveillance de la sensibilité aux antibiotiques des souches de Yersinia pestis à Madagascar de 1989 à 1995. Arch Inst Pasteur Madagascar 1995;62:108-1106
Smith MD ,Vinh DX ,Hoa NTT ,Wain J ,Thung D ,White NJ . In vitro antimicrobial susceptibilities of strains of Yersinia pestis. Antimicrob Agents Chemother 1995;39:2153-2154
Web of Science | Medline7
Frean JA ,Arntzen L ,Capper T ,Bryskier A ,Klugman P . In vitro activities of 14 antibiotics against 100 human isolates of Yersinia pestis from a southern African plague focus. Antimicrob Agents Chemother 1996;40:2646-2647
Web of Science | Medline8
Wood WB . Host specificity of DNA produced by Escherichia coli: bacterial mutations affecting the restriction and modification of DNA. J Mol Biol 1966;16:118-133
CrossRef | Web of Science | Medline9
Sambrook J, Fritsch EF, Maniatis T. Molecular cloning: a laboratory manual. 2nd ed. Plainview, N.Y.: Cold Spring Harbor Laboratory Press, 1989.
10
Datta N ,Hedges RW ,Becker D ,Davies J . Plasmid-determined fusidic acid resistance in the Enterobacteriaceae. J Gen Microbiol 1974;83:191-196
Medline11
Ferber DM ,Brubaker RR . Plasmids in Yersinia pestis. Infect Immun 1981;31:839-841
Web of Science | Medline12
Haas MJ ,Dowding JE . Aminoglycoside-modifying enzymes. Methods Enzymol 1975;43:611-628
CrossRef | Medline13
Courvalin PM ,Shaw WV ,Jacob AE . Plasmid-mediated mechanisms of resistance to aminoglycoside-aminocyclitol antibiotics and to chloramphenicol in group D streptococci. Antimicrob Agents Chemother 1978;13:716-725
Web of Science | Medline14
Poyart-Salmeron C ,Carlier C ,Trieu-Cuot P ,Courtieu AL ,Courvalin P . Transferable plasmid-mediated antibiotic resistance in Listeria monocytogenes. Lancet 1990;335:1422-1426
CrossRef | Web of Science | Medline15
Sanger F ,Nicklen S ,Coulson AR . DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A 1977;74:5463-5467
CrossRef | Web of Science | Medline16
Garrod LP ,Waterworth PM . Methods of testing combined antibiotic bactericidal action and the significance of the results. J Clin Pathol 1962;15:328-338
CrossRef | Web of Science | Medline17
Bukhari AI, Shapiro JA, Adhya SL, eds. DNA insertion elements, plasmids, and episomes. Cold Spring Harbor, N.Y.: Cold Spring Harbor Laboratory, 1977:601-38.
18
Llanes C ,Gabant P ,Couturier M ,Michel-Briand Y . Cloning and characterization of the Inc A/C plasmid RA1 replicon. J Bacteriol 1994;176:3403-3407
Web of Science | Medline19
Sutcliffe JG . Nucleotide sequence of the ampicillin resistance gene of Escherichia coli plasmid pBR322. Proc Natl Acad Sci U S A 1978;75:3737-3741
CrossRef | Web of Science | Medline20
Bennett AD ,Shaw WV . Resistance to fusidic acid in Escherichia coli mediated by the type I variant of chloramphenicol acetyltransferase. Biochem J 1983;215:29-38
Web of Science | Medline21
Bissonnette L ,Roy PH . Characterization of In0 of Pseudomonas aeruginosa plasmid pVS1, an ancestor of integrons of multiresistance plasmids and transposons of gram-negative bacteria. J Bacteriol 1992;174:1248-1257
Web of Science | Medline22
Rasoamanana B ,Coulanges P ,Michel P ,Rasolofonirina N . Sensibilité de Yersinia pestis aux antibiotiques: 277 souches isolées à Madagascar entre 1926 et 1989. Arch Inst Pasteur Madagascar 1989;56:37-53
Medline
- Citing Articles (69)
Citing Articles
1
C. E. Demeure, C. Blanchet, C. Fitting, C. Fayolle, H. Khun, M. Szatanik, G. Milon, J.-J. Panthier, J. Jaubert, X. Montagutelli, M. Huerre, J.-M. Cavaillon, E. Carniel. (2011) Early Systemic Bacterial Dissemination and a Rapid Innate Immune Response Characterize Genetic Resistance to Plague of SEG Mice. Journal of Infectious Diseases
CrossRef2
M. Clarke Miller, Edward DeMoll. 2011. Extraction, Purification, and Identification of Yersiniabactin, the Siderophore of Yersinia pestis. .
CrossRef3
Julian A. Ferreras, Akash Gupta, Neal D. Amin, Arijit Basu, Barij N. Sinha, Stefan Worgall, Venkatesan Jayaprakash, Luis E.N. Quadri. (2011) Chemical scaffolds with structural similarities to siderophores of nonribosomal peptide–polyketide origin as novel antimicrobials against Mycobacterium tuberculosis and Yersinia pestis. Bioorganic & Medicinal Chemistry Letters 21:21, 6533-6537
CrossRef4
E. Boothby, J. C. Shako, E. Bertherat. (2011) Can sputum collection practices for tuberculosis improve laboratory diagnosis of pneumonic plague in developing countries?. Tropical Medicine & International Healthno-no
CrossRef5
Yinon Levy, Yehuda Flashner, Avital Tidhar, Ayelet Zauberman, Moshe Aftalion, Shirley Lazar, David Gur, Avigdor Shafferman, Emanuelle Mamroud. (2011) T cells play an essential role in anti-F1 mediated rapid protection against bubonic plague. Vaccine 29:40, 6866-6873
CrossRef6
Jason A. Rosenzweig, Olufisayo Jejelowo, Jian Sha, Tatiana E. Erova, Sheri M. Brackman, Michelle L. Kirtley, Cristina J. Lier, Ashok K. Chopra. (2011) Progress on plague vaccine development. Applied Microbiology and Biotechnology 91:2, 265-286
CrossRef7
Mitali Sarkar-Tyson, Helen S Atkins. (2011) Antimicrobials for bacterial bioterrorism agents. Future Microbiology 6:6, 667-676
CrossRef8
Anne Derbise, Elisabeth Carniel. (2011) Le diagnostic de la peste. Revue Francophone des Laboratoires 2011:431, 43-50
CrossRef9
C Blanchet, J Jaubert, E Carniel, C Fayolle, G Milon, M Szatanik, J-J Panthier, X Montagutelli. (2011) Mus spretus SEG/Pas mice resist virulent Yersinia pestis, under multigenic control. Genes and Immunity 12:1, 23-30
CrossRef10
Saumya Bhaduri, James L. Smith. (2011) Virulence Plasmid (pYV)-Associated Expression of Phenotypic Virulent Determinants in Pathogenic Yersinia Species: A Convenient Method for Monitoring the Presence of pYV under Culture Conditions and Its Application for Isolation/Detection of Yersinia pestis in Food. Journal of Pathogens 2011, 1-9
CrossRef11
Pep Charusanti, Sadhana Chauhan, Kathleen McAteer, Joshua A Lerman, Daniel R Hyduke, Vladimir L Motin, Charles Ansong, Joshua N Adkins, Bernhard O Palsson. (2011) An experimentally-supported genome-scale metabolic network reconstruction for Yersinia pestis CO92. BMC Systems Biology 5:1, 163
CrossRef12
Giovanna Morelli, Yajun Song, Camila J Mazzoni, Mark Eppinger, Philippe Roumagnac, David M Wagner, Mirjam Feldkamp, Barica Kusecek, Amy J Vogler, Yanjun Li, Yujun Cui, Nicholas R Thomson, Thibaut Jombart, Raphael Leblois, Peter Lichtner, Lila Rahalison, Jeannine M Petersen, Francois Balloux, Paul Keim, Thierry Wirth, Jacques Ravel, Ruifu Yang, Elisabeth Carniel, Mark Achtman. (2010) Yersinia pestis genome sequencing identifies patterns of global phylogenetic diversity. Nature Genetics 42:12, 1140-1143
CrossRef13
Joseph N. Brewoo, Tim D. Powell, Dan T. Stinchcomb, Jorge E. Osorio. (2010) Efficacy and safety of a modified vaccinia Ankara (MVA) vectored plague vaccine in mice. Vaccine 28:36, 5891-5899
CrossRef14
Zunnan Huang, Yantao He, Xian Zhang, Andrea Gunawan, Li Wu, Zhong-Yin Zhang, Chung F. Wong. (2010) Derivatives of Salicylic Acid as Inhibitors of YopH in Yersinia pestis. Chemical Biology & Drug Design 76:2, 85-99
CrossRef15
Julie L. Boyer, Carolina Sofer-Podesta, John Ang, Neil R. Hackett, Maria J. Chiuchiolo, Svetlana Senina, David Perlin, Ronald G. Crystal. (2010) Protective Immunity Against a Lethal Respiratory Yersinia pestis Challenge Induced by V Antigen or the F1 Capsular Antigen Incorporated into Adenovirus Capsid. Human Gene Therapy 21:7, 891-901
CrossRef16
Saumya Bhaduri. (2010) Effect of fat in ground beef on the growth and virulence plasmid (pYV) stability in Yersinia pestis. International Journal of Food Microbiology 136:3, 372-375
CrossRef17
E. P. Savostina, Yu. A. Popov, T. N. Kashtanova, N. A. Vinogradova, O. P. Plotnikova, S. V. Balakhonov. (2009) Genomic polymorphism of strains of basic subspecies of plague causative agent. Molecular Genetics, Microbiology and Virology 24:4, 189-193
CrossRef18
Valentina A Feodorova, Michael J Corbel. (2009) Prospects for new plague vaccines. Expert Review of Vaccines 8:12, 1721-1738
CrossRef19
Deborah M. Anderson, Nancy A. Ciletti, Hanni Lee-Lewis, Derek Elli, Joshua Segal, Kristin L. DeBord, Katie A. Overheim, Maria Tretiakova, Robert R. Brubaker, Olaf Schneewind. (2009) Pneumonic Plague Pathogenesis and Immunity in Brown Norway Rats. The American Journal of Pathology 174:3, 910-921
CrossRef20
Ali Navid, Eivind Almaas. (2009) Genome-scale reconstruction of the metabolic network in Yersinia pestis, strain 91001. Molecular BioSystems 5:4, 368
CrossRef21
Anasuya Chattopadhyay, Steven Park, Guillaume Delmas, Rema Suresh, Svetlana Senina, David S. Perlin, John K. Rose. (2008) Single-dose, virus-vectored vaccine protection against Yersinia pestis challenge: CD4+ cells are required at the time of challenge for optimal protection. Vaccine 26:50, 6329-6337
CrossRef22
Jingfu Qiu, Zhaobiao Guo, Haihong Liu, Dongsheng Zhou, Yanping Han, Ruifu Yang. (2008) DNA microarray-based global transcriptional profiling of Yersinia pestis in multicellularity. The Journal of Microbiology 46:5, 557-563
CrossRef23
SAUMYA BHADURI, CHRISTOPHER H. SOMMERS. (2008) DETECTION OF YERSINIA PESTIS BY COMPARISON OF VIRULENCE PLASMID (PYV/PCD)-ASSOCIATED PHENOTYPES IN YERSINIA SPECIES*. Journal of Food Safety 28:3, 453-466
CrossRef24
Jeremy Leggoe, Chia-bo Chang, Stephen Cox, Steven Presley, Richard Zartman, Tom Gill. 2008. Predicting and Characterizing Threat Transport. , 29-104.
CrossRef25
Karen L. Stirrett, Julian A. Ferreras, Venkatesan Jayaprakash, Barij N. Sinha, Tao Ren, Luis E.N. Quadri. (2008) Small molecules with structural similarities to siderophores as novel antimicrobials against Mycobacterium tuberculosis and Yersinia pestis. Bioorganic & Medicinal Chemistry Letters 18:8, 2662-2668
CrossRef26
Stephen T Smiley. (2008) Current challenges in the development of vaccines for pneumonic plague. Expert Review of Vaccines 7:2, 209-221
CrossRef27
T. Snäll, R. B. O’Hara, C. Ray, S. K. Collinge. (2008) Climate‐Driven Spatial Dynamics of Plague among Prairie Dog Colonies. The American Naturalist 171:2, 238-248
CrossRef28
Nafsika Georgopapadakou. 2007. Antibiotic Resistance in Enterobacteria. , 343-362.
CrossRef29
Michael B Prentice, Lila Rahalison. (2007) Plague. The Lancet 369:9568, 1196-1207
CrossRef30
Amy Palin, Anasuya Chattopadhyay, Steven Park, Guillaume Delmas, Rema Suresh, Svetlana Senina, David S. Perlin, John K. Rose. (2007) An optimized vaccine vector based on recombinant vesicular stomatitis virus gives high-level, long-term protection against Yersinia pestis challenge. Vaccine 25:4, 741-750
CrossRef31
Jonathan N. Lawson, C. Rick Lyons, Stephen Albert Johnston. (2006) Expression Profiling of Yersinia pestis During Mouse Pulmonary Infection. DNA and Cell Biology 25:11, 608-616
CrossRef32
Gerd Prehna, Maya I. Ivanov, James B. Bliska, C. Erec Stebbins. (2006) Yersinia Virulence Depends on Mimicry of Host Rho-Family Nucleotide Dissociation Inhibitors. Cell 126:5, 869-880
CrossRef33
M. Clarke Miller, Sean Parkin, Jacqueline D. Fetherston, Robert D. Perry, Edward DeMoll. (2006) Crystal structure of ferric-yersiniabactin, a virulence factor of Yersinia pestis. Journal of Inorganic Biochemistry 100:9, 1495-1500
CrossRef34
Janak Koirala. (2006) Plague: Disease, Management, and Recognition of Act of Terrorism. Infectious Disease Clinics of North America 20:2, 273-287
CrossRef35
Stephen J. Elvin, James E. Eyles, Kenneth A. Howard, Easwaran Ravichandran, Satyanarayan Somavarappu, H. Oya Alpar, E. Diane Williamson. (2006) Protection against bubonic and pneumonic plague with a single dose microencapsulated sub-unit vaccine. Vaccine 24:20, 4433-4439
CrossRef36
F. Marcos Sánchez, M.I. Albo Castaño, P. del Valle Loarte, D. Joya Seijo. (2006) Infecciones por Yersinia. Medicine - Programa de Formación Médica Continuada Acreditado 9:53, 3449-3455
CrossRef37
W. Mwengee, T. Butler, S. Mgema, G. Mhina, Y. Almasi, C. Bradley, J. B. Formanik, C. G. Rochester. (2006) Treatment of Plague with Gentamicin or Doxycycline in a Randomized Clinical Trial in Tanzania. Clinical Infectious Diseases 42:5, 614-621
CrossRef38
M DAYA, Y NAKAMURA. (2005) Pulmonary Disease from Biological Agents: Anthrax, Plague, Q Fever, and Tularemia. Critical Care Clinics 21:4, 747-763
CrossRef39
J SORABJEE. (2005) Plague. Medicine 33:7, 30-31
CrossRef40
Jingfu Qiu, Dongsheng Zhou, Yanping Han, Ling Zhang, Zongzhong Tong, Yajun Song, Erhei Dai, Bei Li, Jin Wang, Zhaobiao Guo, Junhui Zhai, Zongmin Du, Xiaoyi Wang, Ruifu Yang. (2005) Global gene expression profile of Yersinia pestis induced by streptomycin. FEMS Microbiology Letters 243:2, 489-496
CrossRef41
Johna C. B. DeNap, Paul J. Hergenrother. (2005) Bacterial death comes full circle: targeting plasmid replication in drug-resistant bacteria. Organic & Biomolecular Chemistry 3:6, 959
CrossRef42
J. Steward, M.S. Lever, P. Russell, R.J. Beedham, A.J. Stagg, R.R. Taylor, T.J.G. Brooks. (2004) Efficacy of the latest fluoroquinolones against experimental Yersinia pestis. International Journal of Antimicrobial Agents 24:6, 609-612
CrossRef43
Lyu Jin Jun, Joon Bum Jeong, Min-Do Huh, Joon-Ki Chung, Dong-lim Choi, Chang-Hoon Lee, Hyun Do Jeong. (2004) Detection of tetracycline-resistance determinants by multiplex polymerase chain reaction in Edwardsiella tarda isolated from fish farms in Korea. Aquaculture 240:1-4, 89-100
CrossRef44
Dongsheng Zhou, Yanping Han, Erhei Dai, Yajun Song, Decui Pei, Junhui Zhai, Zongmin Du, Jin Wang, Zhaobiao Guo, Ruifu Yang. (2004) Defining the genome content of live plague vaccines by use of whole-genome DNA microarray. Vaccine 22:25-26, 3367-3374
CrossRef45
Wolf D. Splettstoesser, Lila Rahalison, Roland Grunow, Heinrich Neubauer, Suzanne Chanteau. (2004) Evaluation of a standardized F1 capsular antigen capture ELISA test kit for the rapid diagnosis of plague. FEMS Immunology & Medical Microbiology 41:2, 149-155
CrossRef46
Morad Hassani, Mahesh C Patel, Liise-anne Pirofski. (2004) Vaccines for the prevention of diseases caused by potential bioweapons. Clinical Immunology 111:1, 1-15
CrossRef47
Ronald A Greenfield, Michael S Bronze. (2003) Prevention and treatment of bacterial diseases caused by bacterial bioterrorism threat agents. Drug Discovery Today 8:19, 881-888
CrossRef48
Brendan W. Wren. (2003) The Yersiniae — a model genus to study the rapid evolution of bacterial pathogens. Nature Reviews Microbiology 1:1, 55-64
CrossRef49
Anton V Zavialov, Jenny Berglund, Alexander F Pudney, Laura J Fooks, Tara M Ibrahim, Sheila MacIntyre, Stefan D Knight. (2003) Structure and Biogenesis of the Capsular F1 Antigen from Yersinia pestis. Cell 113:5, 587-596
CrossRef50
Anna M Kauppi, Roland Nordfelth, Hanna Uvell, Hans Wolf-Watz, Mikael Elofsson. (2003) Targeting Bacterial Virulence. Chemistry & Biology 10:3, 241-249
CrossRef51
Y.V.N. Cavalcanti, N.C. Leal, A.M.P. de Almeida. (2002) Typing of Yersinia pestis isolates from the state of Ceara, Brazil. Letters in Applied Microbiology 35:6, 543-547
CrossRef52
B. Joseph Hinnebusch, Marie-Laure Rosso, Tom G. Schwan, Elisabeth Carniel. (2002) High-frequency conjugative transfer of antibiotic resistance genes to Yersinia pestis in the flea midgut. Molecular Microbiology 46:2, 349-354
CrossRef53
E. Navas. (2002) Problems associated with potential massive use of antimicrobial agents as prophylaxis or therapy of a bioterrorist attack. Clinical Microbiology and Infection 8:8, 534-539
CrossRef54
E Carniel. (2002) La pesteThe plague.. Comptes Rendus Biologies 325:8, 851-853
CrossRef55
Michel Drancourt, Didier Raoult. (2002) Molecular insights into the history of plague. Microbes and Infection 4:1, 105-109
CrossRef56
Ethan Rubinstein, Itzhak Levi. (2002) Biological warfare: Implications for antimicrobial use. Current Infectious Disease Reports 4:1, 28-34
CrossRef57
Marc Lipsitch. (2001) The rise and fall of antimicrobial resistance. Trends in Microbiology 9:9, 438-444
CrossRef58
Richard W Titball, E.Diane Williamson. (2001) Vaccination against bubonic and pneumonic plague. Vaccine 19:30, 4175-4184
CrossRef59
Jehangir S Sorabjee. (2001) Plague. Medicine 29:5, 23-24
CrossRef60
Raul E. Isturiz, Claude Carbon. (2000) Antibiotic Use in Developing Countries • . Infection Control and Hospital Epidemiology 21:6, 394-397
CrossRef61
Suzanne Chanteau, Mahery Ratsitorahina, Lila Rahalison, Bruno Rasoamanana, Fabien Chan, Pascal Boisier, Dieudoné Rabeson, Jean Roux. (2000) Current epidemiology of human plague in Madagascar. Microbes and Infection 2:1, 25-31
CrossRef62
Mahery Ratsitorahina, Suzanne Chanteau, Lila Rahalison, Lala Ratsifasoamanana, Pascal Boisier. (2000) Epidemiological and diagnostic aspects of the outbreak of pneumonic plague in Madagascar. The Lancet 355:9198, 111-113
CrossRef63
Viviane Chenal-Francisque, Lise Tourneux, Elisabeth Carniel, Petya Christova, Ines Li de la Sierra, Octavian Barzu, Anne-Marie Gilles. (1999) The highly similar TMP kinases of Yersinia pestis and Escherichia coli differ markedly in their AZTMP phosphorylating activity. European Journal of Biochemistry 265:1, 112-119
CrossRef64
Marie-Anne Arcangioli, Sabine Leroy-Sétrin, Jean-Louis Martel, Elisabeth Chaslus-Dancla. (1999) A new chloramphenicol and florfenicol resistance gene flanked by two integron structures in Salmonella typhimurium DT104. FEMS Microbiology Letters 174:2, 327-332
CrossRef65
Jack A. Heinemann. (1999) How antibiotics cause antibiotic resistance. Drug Discovery Today 4:2, 72-79
CrossRef66
Janelle M. Hare, Alexandra K. Wagner, Kathleen A. McDonough. (1999) Independent acquisition and insertion into different chromosomal locations of the same pathogenicity island in Yersinia pestis and Yersinia pseudotuberculosis. Molecular Microbiology 31:1, 291-303
CrossRef67
(1998) REVIEW OF CURRENT LITERATURE. Journal of Travel Medicine 5:2, 106-106
CrossRef68
Joseph B McCormick. (1998) Epidemiology of emerging/re-emerging antimicrobial-resistant bacterial pathogens. Current Opinion in Microbiology 1:1, 125-129
CrossRef69
Dennis, David T., , Hughes, James M., . (1997) Multidrug Resistance in Plague. New England Journal of Medicine 337:10, 702-704
Full Text
