Evaluation of Intraspecies Interference Due to agr Polymorphism in Staphylococcus Aureus during Infection and Colonization

Journal of Infectious Diseases, Jul 2003

In Staphylococcus aureus infection, intraspecies cross-inhibition mediated by the regulatory system agr may lead to the exclusion of heterologous strains at the site of infection or colonization. We analyzed consecutive and cocolonizing strains (classified as different clones by pulsed-field gel electrophoresis) from patients with cystic fibrosis (CF) and healthy individuals. Strain replacement was accompanied by a change in the agrgroup in 80% of the patients with CF and in 63% of the healthy individuals. Cocolonizing strains from patients with CF were shown to belong to interfering agr groups in 6 of 10 cases. In contrast, in healthy individuals, cocolonization of the nares with strains of interfering agr groups was rarely observed. agr polymorphism has no impact on the colonization dynamics of S. aureus in patients with CF but may influence nasal colonization in health individuals.

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Evaluation of Intraspecies Interference Due to agr Polymorphism in Staphylococcus Aureus during Infection and Colonization

Christiane Goerke Mirjam K ummel Klaus Dietz Christiane Wolz Instituts for Allgemeine Hygiene und Umwelthygiene Medizinische Biometrie Universitat Tubingen Tubingen Germany In Staphylococcus aureus infection, intraspecies cross-inhibition mediated by the regulatory system agr may lead to the exclusion of heterologous strains at the site of infection or colonization. We analyzed consecutive and cocolonizing strains (classified as different clones by pulsed-field gel electrophoresis) from patients with cystic fibrosis (CF) and healthy individuals. Strain replacement was accompanied by a change in the agr group in 80% of the patients with CF and in 63% of the healthy individuals. Cocolonizing strains from patients with CF were shown to belong to interfering agr groups in 6 of 10 cases. In contrast, in healthy individuals, cocolonization of the nares with strains of interfering agr groups was rarely observed. agr polymorphism has no impact on the colonization dynamics of S. aureus in patients with CF but may influence nasal colonization in health individuals. - The major human pathogen Staphylococcus aureus asymptomatically colonizes the anterior nares of humans but also causes a wide spectrum of diseases [1]. S. aureus infections are probably established via the coordinated synthesis of extracellular and cell-bound virulence factors [2]. The expression of most virulence factors is controlled by global regulators, such as agr. The agr locus, which consists of 5 genes (agrA, agrC, agrD, agrB, and hld), codes for 2 divergent transcripts (RNAII and RNAIII) initiated by 2 distinct promoters (P2 and P3). RNAIII is the effector molecule, exhibiting a positive regulatory effect on extracellular proteins, such as a-hemolysin, and a negative regulatory effect on protein A and fibronectin-binding proteins [36]. agrA shows sequence homology to the response regulator, whereas agrC corresponds to the histidine protein kinase signal transducer [7] of the classic 2-component regulatory system [8]. agrD encodes an extracellular octapeptide, known as the autoinducing peptide (AIP), which operates in a quorum-sensing system [9, 10], thus explaining the growth-phasedependent expression of agr-regulated genes. agrC binds the AIP [11] and may subsequently phosphorylate AgrA. P2 and P3 are both thought to be autocatalytically activated by phosphorylated AgrA [7]. The sequence of the AIP and its receptor, agrC, is highly variable, resulting in at least 4 specificity groups within S. aureus [12, 13]. AIPs activate their specific receptors while inhibiting activation of AgrC in strains of other specificity groups. This inhibition is a form of bacterial interference that does not result in mutual growth inhibition but, instead, in the blocking of virulence gene expression. This phenomenon has been discussed as a new bacterial strategy for excluding other strains of the same species from the infection or colonization site [12]. However, such intrastrain interference during colonization and infection has never been actually demonstrated in the human host. Surveys of agr group distribution in naturally occurring S. aureus strains have been done mainly with methicillin-resistant S. aureus (MRSA) [14, 15] and with strains isolated from various infections sites [16, 17]. Information on agr group distribution of nasal carrier strains in the community is limited [18]. We wanted to analyze whether intraspecies cross-inhibition of agr expression leads to the exclusion of heterologous strains at the site of colonization or infection. For this purpose, agr polymorphism in consecutive and cocolonizing S. aureus strains was assessed. We compared S. aureus isolates obtained from patients with chronic infection (lung infection in patients with cystic fibrosis [CF]) with isolates from nose colonization in healthy individuals in the community. The prevalence of agr group IIV strains also was determined in intubated patients from an intensive care unit (ICU) and in patients with chronic wounds. MATERIALS AND METHODS Strain collection. S. aureus isolates were collected from 133 individuals: 35 nonhospitalized patients with CF (sputum samples), 30 intubated patients in an ICU (tracheal secretions), 31 patients from an out-patient wound consultation clinic (wound swabs), and 37 healthy control subjects (nose swabs). Patients with CF attended the CF center in Tu bingen quarterly for regular check-ups. Antibiotics were prescribed according to the standard guidelines of the center. Patients in the ICU were admitted to this ward after major surgeries. All had received prophylactic antibiotic treatment. Tracheal secretions were obtained 25 days after intubation. The category of wound patients mainly consisted of patients with diabetes mellitus. In all but 2 cases, the S. aureuspositive wound swabs were not accompanied by inflammatory signs, and no antibiotic treatment was applied. The healthy individuals included family members from a study with CF and non-C (...truncated)


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Christiane Goerke, Mirjam Kümmel, Klaus Dietz, Christiane Wolz. Evaluation of Intraspecies Interference Due to agr Polymorphism in Staphylococcus Aureus during Infection and Colonization, Journal of Infectious Diseases, 2003, pp. 250-256, 188/2, DOI: 10.1086/376450