Relationships between Staphylococcus aureus Genetic Background, Virulence Factors, agr Groups (Alleles), and Human Disease

ABSTRACT The expression of most Staphylococcus aureus virulence factors is controlled by the agr locus, which encodes a two-component signaling pathway whose activating ligand is an agr-encoded autoinducing peptide (AIP). A polymorphism in the amino acid sequence of the AIP and of its corresponding receptor divides S. aureus strains into four major groups. Within a given group, each strain produces a peptide that can activate the agr response in the other member strains, whereas the AIPs belonging to different groups are usually mutually inhibitory. We investigated a possible relationship between agr groups and human S. aureus disease by studying 198 S. aureus strains isolated from 14 asymptomatic carriers, 66 patients with suppurative infection, and 114 patients with acute toxemia. The agr group and the distribution of 24 toxin genes were analyzed by PCR, and the genetic background was determined by means of amplified fragment length polymorphism (AFLP) analysis. The isolates were relatively evenly distributed among the four agrgroups, with 61 strains belonging to agr group I, 49 belonging to group II, 43 belonging to group III, and 45 belonging to group IV. Principal coordinate analysis performed on the AFLP distance matrix divided the 198 strains into three main phylogenetic groups, AF1 corresponding to strains of agr group IV, AF2 corresponding to strains of agr groups I and II, and AF3 corresponding to strains of agr group III. This indicated that the agr type was linked to the genetic background. A relationship between genetic background, agr group, and disease type was observed for several toxin-mediated diseases: for instance, agr group IV strains were associated with generalized exfoliative syndromes, and phylogenetic group AF1 strains with bullous impetigo. Among the suppurative infections, endocarditis strains mainly belonged to phylogenetic group AF2 and agr groups I and II. While these results do not show a direct role of the agr type in the type of human disease caused by S. aureus, the agr group may reflect an ancient evolutionary division of S. aureus in terms of this species’ fundamental biology.

[1]  P. Desjardins,et al.  Sex in Escherichia coli does not disrupt the clonal structure of the population: evidence from random amplified polymorphic DNA and restriction-fragment-length polymorphism , 1995, Journal of Molecular Evolution.

[2]  William,et al.  Recombination and Population Structure in Escherichia coli , 2002 .

[3]  F. Vandenesch,et al.  Experimental and theoretical evaluation of typing methods based upon random amplification of genomic restriction fragments (AFLP) for bacterial population genetics , 2001, Genetics Selection Evolution.

[4]  B. Cookson Whole genome sequencing of methicillin resistant Staphylococcus aureus , 2001 .

[5]  M. Kanehisa,et al.  Whole genome sequencing of meticillin-resistant Staphylococcus aureus , 2001, The Lancet.

[6]  B. Spratt,et al.  A Link Between Virulence and Ecological Abundance in Natural Populations of Staphylococcus aureus , 2001, Science.

[7]  M. Gilmore,et al.  Michelle Various Sites of Infection Isolates from Staphylococcus aureus Clonal Associations among , 2000 .

[8]  F. Vandenesch,et al.  egc, A Highly Prevalent Operon of Enterotoxin Gene, Forms a Putative Nursery of Superantigens in Staphylococcus aureus , 2001, The Journal of Immunology.

[9]  A. van Belkum,et al.  Population Studies of Methicillin-Resistant and -Sensitive Staphylococcus aureus Strains Reveal a Lack of Variability in the agrD Gene, Encoding a Staphylococcal Autoinducer Peptide , 2000, Journal of bacteriology.

[10]  M. Tibayrenc,et al.  Prevalence of Virulence Genes and Clonality inEscherichia coli Strains That Cause Bacteremia in Cancer Patients , 2000, Infection and Immunity.

[11]  F. Vandenesch,et al.  Involvement of Panton-Valentine leukocidin-producing Staphylococcus aureus in primary skin infections and pneumonia. , 1999, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[12]  Jacques Elion,et al.  The Link between Phylogeny and Virulence inEscherichia coli Extraintestinal Infection , 1999, Infection and Immunity.

[13]  P. Desjardins,et al.  Phylogenetic analysis of Escherichia coli strains causing neonatal meningitis suggests horizontal gene transfer from a predominant pool of highly virulent B2 group strains. , 1998, The Journal of infectious diseases.

[14]  F. Vandenesch,et al.  Toxin involvement in staphylococcal scalded skin syndrome. , 1997, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[15]  R. Beavis,et al.  Bacterial interference caused by autoinducing peptide variants. , 1997, Science.

[16]  S. Falkow What is a pathogen , 1997 .

[17]  Jean Thioulouse,et al.  ADE-4: a multivariate analysis and graphical display software , 1997, Stat. Comput..

[18]  T. Whittam,et al.  Clonal relationships among bloodstream isolates of Escherichia coli , 1995, Infection and immunity.

[19]  P. Vos,et al.  AFLP: a new technique for DNA fingerprinting. , 1995, Nucleic acids research.

[20]  R. Haug New criteria for diagnosis of infective endocarditis: Utilization of specific echocardiographic findings , 1994 .

[21]  S. Dolédec,et al.  Co‐inertia analysis: an alternative method for studying species–environment relationships , 1994 .

[22]  D. Durack,et al.  New criteria for diagnosis of infective endocarditis: utilization of specific echocardiographic findings. Duke Endocarditis Service. , 1994, The American journal of medicine.

[23]  J. M. Smith,et al.  How clonal are bacteria? , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[24]  D. Coleman,et al.  Staphylococcal toxins in human disease. , 1990, Society for Applied Bacteriology symposium series.

[25]  J. Musser,et al.  A single clone of Staphylococcus aureus causes the majority of cases of toxic shock syndrome. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[26]  M. D. Buyser,et al.  Characterization of Staphylococcus species by ribosomal RNA gene restriction patterns. , 1989, Journal of general microbiology.

[27]  H. Sambrook Molecular cloning : a laboratory manual. Cold Spring Harbor, NY , 1989 .

[28]  J. Gower Some distance properties of latent root and vector methods used in multivariate analysis , 1966 .