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New Insights into Mechanisms of Human-Bovine Host Jump of Staphylococcus aureus Clonal Cluster CC8

English title New Insights into Mechanisms of Human-Bovine Host Jump of Staphylococcus aureus Clonal Cluster CC8
Applicant Moreillon Philippe
Number 143650
Funding scheme Project funding
Research institution Département de Microbiologie Fondamentale Faculté de Biologie et de Médecine Université de Lausanne
Institution of higher education University of Lausanne - LA
Main discipline Medical Microbiology
Start/End 01.11.2012 - 31.07.2017
Approved amount 430'000.00
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Keywords (1)

Staphylococcal human-to-bovine jump

Lay Summary (English)

Lead
Lay summary

Understanding cross-species jump of bacterial pathogens – in this case Staphylococcus aureus – is a nagging question that has precedents in human and poultry and human and pigs. We recently described a human-bovine host jump of S. aureus CC8, a lineage that contains the notoriously virulent methicillin-resistant S. aureus (MRSA) USA300. Here we propose to study in depth the genomic and mechanistic correlates underlying this jump. The opportunity is unique for at least two reasons. First, it occurred rather recently and therefore the microbial genomes are not biased by prolonged divergent evolution. Second, the genetic differences between bovine and human isolates are still relatively circumscribed. They implicate two main Mobile Genetic Elements (MGEs), i.e. (i) the gain of a new MGE carrying a new surface protein that might promote S. aureus establishment in cows, and (ii) the loss of prophage phiSA3, which is important for S. aureus colonization of humans. Understanding the CC8 human-bovine jump is very attractive from both the veterinary and human medicine points of view. Indeed, bovine S. aureus CC8 appeared more aggressive than typical bovine S. aureus in herds. Thus, the detection of CC8 clones in mastitis should warn veterinarians for scrutiny. Moreover, the new MGE of bovine CC8 isolates may convey important antibiotic-resistance determinants (e.g. methicillin-resistance) back into humans. Thus, studying the CC8 human-to-bovine host jump does not only represent an academic opportunity to understand biology, but also to learn more on veterinary and human epidemiology in order to prevent the spread of infectious diseases and antibiotic-resistance.

Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Development of a new real-time quantitative PCR assay for the detection of Staphylococcus aureus genotype B in cow milk, targeting the new gene adlb.
Sartori C, Boss R, Ivanovic I, Graber H U (2017), Development of a new real-time quantitative PCR assay for the detection of Staphylococcus aureus genotype B in cow milk, targeting the new gene adlb., in Journal of dairy science, 100(10), 7834-7845.
Human-to-bovine jump of Staphylococcus aureus CC8 is associated with the loss of a β-hemolysin converting prophage and the acquisition of a new staphylococcal cassette chromosome.
Resch Grégory, François Patrice, Morisset Delphine, Stojanov Milos, Bonetti Eve J, Schrenzel Jacques, Sakwinska Olga, Moreillon Philippe (2013), Human-to-bovine jump of Staphylococcus aureus CC8 is associated with the loss of a β-hemolysin converting prophage and the acquisition of a new staphylococcal cassette chromosome., in PloS one, 8(3), 58187-58187.

Collaboration

Group / person Country
Types of collaboration
Dr. Olga Sakwinska, Nestlé Research Centre, Vers-chez-les-Blanc Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Dr. HDR Marisa Haenni, Agence Nationale de Sécurité Alimentaire (AFFSA), Lyon France (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Dr. Ruth Heying, University of Leuven, Leuven Belgium (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
SYMPOSTAPH, Société française de microbiologie Individual talk Host jump of human Staphylococcus aureus CC8 to cows is associated with the acquisition of a non-mecA staphylococcal cassette chromosome (SCC) 26.10.2016 Lyon, France Moreillon Philippe; Steiner Théodora;
ISSSI (International Symposium on Staphylococci and Staphylococcal Diseases) Poster Host jump of human S. aureus CC8 to cows is associated with the acquisition of a non-mecA staphylococcal cassette chromosome (SCC). 30.08.2016 Seoul, Korean Republic (South Korea) Moreillon Philippe;
ISSSI (International Symposium on Staphylococci and Staphylococcal Diseases) Individual talk The rate of excision of staphylococcal cassette chromosome (SCC) is regulated by the presence of integrated prophages 30.08.2016 Seoul, Korean Republic (South Korea) Moreillon Philippe;
ISSSI (International Symposium on Staphylococci and Staphylococcal Diseases) Poster A new surface protein possibly involved in adaptation of human Staphylococcus aureus CC8 to the bovine environment 30.08.2016 Seoul, Korean Republic (South Korea) Moreillon Philippe;
ISSSI (International Symposium on Staphylococci and Staphylococcal Diseases) Poster The rate of excision of staphylococcal cassette chromosome (SCC) is regulated by the presence of integrated prophages 30.08.2016 Seoul, Korean Republic (South Korea) Moreillon Philippe;
Nutztierabend, Wiederkäuerklinik Vetsuisse-Fakultät Bern Poster Genotypen von Staphylococcus aureus: Ihr Vorkommen auf Milchkühen und deren Umgebung 14.05.2015 Bern, Switzerland Spycher Anita; Graber Hans Uldrich;
SYMPOSTAPH, Société française de microbiologie Talk given at a conference Nouvelle protéine possiblement de Staphylococcus aureus possiblement impliquée dans le transfert inter-espèce de l’homme à la vache 20.10.2014 Lyon, France Moreillon Philippe;
SSM (Swiss society for microbiology) annual meeting Poster A new surface protein possibly involved in bovine adaptation of Staphylococcus aureus CC8 strains originating from human 27.05.2014 Lugano, Switzerland Moreillon Philippe;


Associated projects

Number Title Start Funding scheme
65371 Studying Staphylococcus aureus pathogenic determinants by trans- fer and expression in less virulent bacteria. Molecular analysis and relevance in the model of experimental endocarditis in vivo. 01.10.2001 Project funding
113854 Pathogenesis of Staphylococcus aureus Experimental Infection: Diversity and Function of Virulence Genes in Bacterial Isolates form human and Animal Origin 01.01.2007 Project funding

Abstract

1. SUMMARYThe present proposal aims to understand the fascinating ability of S. aureus to colonize and adapt successively to different hosts, using the recent human-bovine jump of S. aureus clonal cluster CC8 as a model system. Understanding cross-species jump of S. aureus is a nagging question that has recent precedents in human and poultry and human and pigs. During host jump, S. aureus may acquire movable genetic elements (MGEs) that confer it indispensable features to survive in the new host, or lose elements that are indispensable to colonize the first host but became deleterious in the new one. This is exemplified by the acquisition of prophage phiSAB during the passage from human to poultry, and the loss of phiSA3 - which is important to colonize humans but not animals - during the passage from human to poultry or human to pigs. Moreover, along its journey from one host to another, S. aureus may also acquire additional genes, such antibiotic-resistance genes or toxin genes. These more generalist genes may become problematic for the whole human and veterinary medical community. We recently described a human-bovine host jump of S. aureus CC8, a lineage that contains the notoriously virulent methicillin-resistant S. aureus (MRSA) USA300. Here we propose to study in depth the genomic and mechanistic correlates underlying this jump. The opportunity is unique for several reasons. First, it occurred rather recently and therefore the microbial genomes are not biased by prolonged divergent evolution. Second, the genetic differences between bovine and human isolates are still relatively circumscribed. They implicate two main MGEs, i.e. a new staphylococcal chromosome cassette (SCC) devoid of mecA but carrying a new LPXTG protein, and the loss of phiSA3. Third, we have the genetic and molecular tools to test the implications of these elements for host specificity as a whole. Fourth, the event is apparently predominant in Switzerland, and we have acquired a large collection of CC8 isolates from both bovine and human origin.We plan a four-step experimental schedule. First by generalizing genomic comparison (for SCC, phiSA3 and other differences) to a whole collection of bovine and human CC8 isolates via microarray-analysis and total genome sequencing. Second, by comparing phenotypes of bovine and human CC8 isolates, including gene expression at the mRNA and proteomic levels, and comparing in vitro and ex vivo colonization and invasion properties in tissue cultures. Third, by constructing recombinant S. aureus deleted or complemented in SCC or phiSA3, and expressing relevant genes heterologously in L. lactis to clarify their function in phenotypic tests. Fourth by completing a new field study to learn more on the epidemiological makeup of bovine and human CC8 in the farm environment, especially regarding to the reservoir of strains and the reservoir of the SCC cassette.Understanding the CC8 human-bovine jump is very attractive from both the biology and veterinary and human medicine points of view. Indeed, bovine CC8 appear more aggressive than typical bovine CCs in herds. Thus, the detection of CC8 clones in mastitis should warn veterinarians for scrutiny. Moreover, bovine CC8 carry a SCC cassette, which may pose three additional problems. First, it is a close homolog of SCCmec cassettes found in human MRSA (e.g. USA300 and COL), and could very well acquire the mecA element or other antibiotic resistance or virulence genes along evolution, which could then lead to a bovine-MRSA epidemic. Second, because SCC is mobile, it could be passed to other bovine CCs. Finally, because CC8 presumably jumped from humans to cows, it could possibly make the reverse jump and carry new SCCmec cassette into human medicine, similarly to well-known swine CC398. For all these reasons, studying the CC8 human-to-bovine host jump does not only represent an academic opportunity to understand biology, but also to learn more on human and veterinary epidemiology in order to prevent the spread of infectious diseases and antibiotic-resistance.
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