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Paris, August 3, 2011

The troubling emergence of multi-drug resistant Salmonella

As part of a vast international study, researchers from the Institut Pasteur, the INRA and the French Institute for Public Health Surveillance have tracked the sudden and worrying emergence of a Salmonella strain that has developed resistance to almost every possible antibiotic treatment. The study has retraced the evolution of the bacteria throughout the last 50 years. It has notably determined the chronology for the appearance of different resistances, decrypted the bacteria’s mechanisms, and identified poultry to be the main vector of the strain. This work, published in the Journal of Infectious Diseases, underlines the importance of closely monitoring these bacteria responsible for food-borne infections and the need to rationalize the use of antibiotics in farming at the international level.

Salmonella bacteria represent one of the primary causes of food-borne infections in humans. Microbiological monitoring of human infections in France is run by the French National Reference Center (CNR) for Salmonella, at the Institut Pasteur, in collaboration with the epidemiologists of the French Institute for Public Health Surveillance. The CNR had recently detected the very early emergence, from 2002, of a type of Salmonella affecting a small number of travelers returning from Egypt, Kenya, and Tanzania. This bacteria, called “Salmonella Kentucky” showed resistance to numerable antibiotics, notably fluoroquinolone, currently one of the key treatments in severe Salmonella infections.

In order to measure and follow the spread of the phenomenon on a larger scale, the CNR team from the Institut Pasteur, headed by François-Xavier Weill and Simon Le Hello, undertook a vast international study uniting a dozen different public health and research institutions in Europe, the United States, and Africa.

The epidemiological data collected has enabled researchers to track the spectacular explosion of this bacteria in real-time starting from 2006. Between 2002 and 2008, 500 cases over all were recorded in France, the United Kingdom, and Denmark. For France alone, between 2009 and 2010, 270 cases were confirmed. Furthermore, the contamination zone, initially limited to East and North-East Africa, has progressively spread to North and West Africa, as well as to the Middle East.

In collaboration with an INRA team from Tours, France, headed by Axel Cloeckaert of the “Animal Infectious Diseases and Veterinary Public Health” research unit, CNR for Salmonella researchers have also focused on studying the genetics of the original bacteria strains from the different geographical regions as well as those that have been preserved for several Press release. decades in collections at the Institut Pasteur. They have thus decrypted the antibiotic resistance mechanisms and used them to retrace the chronology. At the beginning of the 1990’s a DNA fragment containing genes resistant to six molecules, some of which were already widely used at the time, was integrated into a Salmonella Kentucky chromosome. In the mid 1990’s mutations in different genes led to quinolone resistance and then at the beginning of the 2000s to fluoroquinolone resistance.

The researchers’ observations seem to indicate that Egypt may be the geographical birthplace of the three steps of emergence of antibiotic resistance. It is there that all of the genetic modifications at the source of these resistances were identified for the first time.

Researchers consider that Salmonella Kentucky probably acquired the DNA fragment responsible for the first resistances via aquaculture systems. The widespread use of antibiotics in farming in Egypt since the early 1990’s appears to have favored the natural selection of bacteria strains with this antibiotic resistance. The recent explosion of cases would then be linked to the spread of the bacteria in Africa within the poultry industry, a major consumer of fluoroquinolones. The accumulation of all these resistances on the same strain of Salmonella Kentucky would therefore appear to be the source of the current epidemic.

The emergence of such a multidrug-resistant Salmonella Kentucky strain worries scientists. Today, in over 10% of cases, patients have not declared stays abroad. According to these signs, the bacteria is beginning to take root in Europe, therefore multiplying the risk of contamination in farmed poultry and threatening its spread on a large scale. Moreover, researchers at the Institut Pasteur have recently shown the existence of several Salmonella Kentucky isolates resistant to third generation cephalosporins and carbapenems in North Africa. These antibiotics constitute the last therapeutic protection against the bacteria. As such, the spread of resistance to the epidemic Salmonella Kentucky strain would represent an impasse in the treatment of these infections.

The results of this study underline the importance of microbiological monitoring on both national and international levels, in particular for southern countries. They are a reminder of the public health risks of non-regulated use of antibiotics in the farming industry which promotes the appearance and spread of resistant genes in bacteria responsible for foodborne infections.

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Picture: Salmonella bacteria © Institut Pasteur.


For more information


Source

International spread of an epidemic population of Salmonella enterica serotype Kentucky ST198 resistant to ciprofloxacin, Journal of Infectious Diseases, August 4, 2011.
Simon Le Hello, Pharm.D, M.Sc (1), Rene S. Hendriksen Ph.D (2), Benoît Doublet Ph.D (3), Ian Fisher (4), Eva Møller Nielsen Ph.D (5), Jean M. Whichard, D.V.M, Ph.D (6), Brahim Bouchrif Ph.D (7), Kayode Fashae M.Sc (8), Sophie A.Granier Ph.D (9), Nathalie Jourdan-Da Silva, M.D, M.P.H (10), Axel Cloeckaert, Ph.D (3), E. John Threlfall Ph.D (4), Frederick. J. Angulo, D.V.M, Ph.D (6), Frank M. Aarestrup D.V.M, Ph.D (2), John Wain, Ph.D (4), François-Xavier Weill, M.D, Ph.D (1).

(1) Institut Pasteur, Enteric Bacterial Pathogens Unit, French National Reference Center for Salmonella, WHO Collaborating Centre for Reference and Research on Salmonella, Paris 75015, France.
(2) WHO Collaborating Centre for Antimicrobial Resistance in Food-Borne pathogens and EU Community Reference Laboratory for Antimicrobial Resistance, National Food Institute, Technical University of Denmark, Copenhagen V DK-1790, Denmark.
(3) INRA, UR1282, Animal Infectious Diseases and Veterinary Public Health, Nouzilly F-37380, France.
(4) Health Protection Agency, Laboratory for Gastrointestinal Infections, Centre for Infections, London NW9 5EQ, United Kingdom. (5) Statens Serum Institute, Dept. Microbiological Surveillance and Research, Copenhagen DK-2300, Denmark.
(6) Division of Foodborne, Bacterial and Mycotic Diseases, Centers for Disease Control and Prevention, Atlanta GA 30033, USA. 18 Institut Pasteur in Morocco, Casablanca, Morocco.
(7) Institut Pasteur of Marocco, Casablanca, Morocco.
(8) University of Ibadan, Department of Microbiology, Nigeria.
(9) French Agency for Food, Environmental and Occupational Health and Safety, Laboratory for Study and Research on Food Quality and Processing (LERQAP), Bacterial Characterization and Epidemiology Unit, Maisons-Alfort F-94706, France. Source For more information
(10) French Institute for Public Health Surveillance (InVS) Department of Infectious diseases, Saint-Maurice F-94415, France.

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