Polymorphisms of agr locus correspond to distinct genetic patterns of virulence in Staphylococcus aureus clinical isolates from orthopedic implant infections.
ABSTRACT Staphylococcus aureus is the leading etiologic agent of orthopedic implant infections. It is endowed with the accessory gene regulator (agr) locus that modulates expression of many virulence genes. Four allelic groups of agr have been recognized within this bacterial species. Here, 200 S. aureus isolates from orthopedic implant infections, typed at the start depending on their agr group, were screened for the presence of adhesin and leukotoxin genes. Interestingly, specific virulence gene patterns emerged in association with agr groups. The most frequently observed agr groups, agr I and agr II, were associated with the presence of sdrE, fib (agr II more than agr I), fnbB (agr I more than agr II), and lukE/lukD (agr II more than agr I). The third more frequent agr group, agr III, differed clearly from agr I and II, exhibiting high prevalence of bbp, generally not harbored by agr I and II, and copresence of bbp with cna, whereas high prevalence of the tandem sdrE/fib marked definitely agr II (91% of agr II isolates), and, though less strictly, agr I, in which prevailed the peculiar fib/fnbB pattern. The only four isolates belonging to agr IV showed full copresence of bbp with fib. Results point out distinct patterns of virulence genes, which underlie distinct evolutive strategies associated to agr groups in S. aureus causing orthopedic implant infections.
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ABSTRACT: The sdr locus was found in all 497 investigated Staphylococcus aureus strains, although in 29 strains it contained only the sdrC gene (sdrD negative, sdrE negative). The sdrC-positive, sdrD-negative, sdrE-negative gene profile was exclusive to methicillin-sensitive S. aureus (MSSA) strains (Fisher's exact test; P = 0.0005) and was not found in the strains collected from bone infections (P = 0.0019). We also found a strong association between the presence of the sdrD gene and methicillin-resistant S. aureus strains (P < 0.0001). Our findings suggest that MSSA strains with the newly uncovered sdrC-positive, sdrD-negative, sdrE-negative gene profile have a substantially decreased potential to establish bone infection.Journal of Clinical Microbiology 03/2006; 44(3):1135-8. · 4.07 Impact Factor
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ABSTRACT: The impact of bacterial genetic characteristics on the outcome of patients with Staphylococcus aureus infections is uncertain. This investigation evaluated potential associations between bacterial genotype and clinical outcome using isolates collected as part of an international phase 2 clinical trial (FAST II) evaluating telavancin for the treatment of complicated skin and skin structure infections (cSSSI). Ninety S. aureus isolates from microbiologically evaluable patients with cSSSI enrolled in the FAST II trial from 11 sites in the United States (56 isolates, or 62%) and 7 sites in South Africa (34 isolates, or 38%) were examined for staphylococcal cassette chromosome mec, agr, and the presence of 31 virulence genes and subjected to pulsed-field gel electrophoresis (PFGE). South African methicillin-susceptible S. aureus (MSSA) isolates were more likely to carry certain virulence genes, including sdrD (P = 0.01), sea (P < 0.01), and pvl (P = 0.01). All 44 (49%) methicillin-resistant S. aureus (MRSA) isolates were from the United States; 37 (84%) were strain USA 300 by PFGE. In the United States, MRSA isolates were more likely than MSSA isolates to carry genes for sdrC (P = 0.03), map/eap (P = 0.05), fnbB (P = 0.11), tst (P = 0.02), sea (P = 0.04), sed (P = 0.04), seg (P = 0.11), sej (P = 0.11), agr (P = 0.09), V8 (P = 0.06), sdrD, sdrE, eta, etb, and see (P < 0.01 for all). MRSA isolates were more often clonal than MSSA isolates by PFGE. Isolates from patients who were cured were significantly more likely to contain the pvl gene than isolates from patients that failed or had indeterminate outcomes (79/84 [94%] versus 3/6 [50%]; P = 0.01). S. aureus strains from different geographic regions have different distributions of virulence genes.Journal of clinical microbiology 02/2008; 46(2):678-84. · 4.16 Impact Factor
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ABSTRACT: TraP is a triply phosphorylated staphylococcal protein that has been hypothesized to be the mediator of a second Staphylococcus aureus quorum-sensing system, "SQS1," that controls expression of the agr system and therefore is essential for the organism's virulence. This hypothesis was based on the loss of agr expression and virulence by a traP mutant of strain 8325-4 and was supported by full complementation of both phenotypic defects by the cloned traP gene in strain NB8 (Y. Gov, I. Borovok, M. Korem, V. K. Singh, R. K. Jayaswal, B. J. Wilkinson, S. M. Rich, and N. Balaban, J. Biol. Chem. 279:14665-14672, 2004), in which the wild-type traP gene was expressed in trans in the 8325-4 traP mutant. We initiated a study of the mechanism by which TraP activates agr and found that the traP mutant strain used for this and other recently published studies has a second mutation, an adventitious stop codon in the middle of agrA, the agr response regulator. The traP mutation, once separated from the agrA defect by outcrossing, had no effect on agr expression or virulence, indicating that the agrA defect accounts fully for the lack of agr expression and for the loss of virulence attributed to the traP mutation. In addition, DNA sequencing showed that the agrA gene in strain NB8 (Gov et al., J. Biol. Chem., 2004), in contrast to that in the agr-defective 8325-4 traP mutant strain, had the wild-type sequence; further, the traP mutation in that strain, when outcrossed, also had no effect on agr expression.Infection and Immunity 10/2007; 75(9):4534-40. · 4.07 Impact Factor