Chromosomal rearrangements affecting biofilm production and antibiotic resistance in a Staphylococcus epidermidis strain causing shunt-associated ventriculitis

Ziebuhr, Wilma; Dietrich, Katja; Trautmann, Matthias; Wilhelm, Martin

doi:10.1016/s1438-4221(00)80115-0

Cited by 53 publications

(37 citation statements)

References 23 publications

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“…IS256 is an insertion sequence element which is part of the aminoglycoside resistancemediating transposon Tn4001 but also occurs independently in multiple copies in the genomes of staphylococci and enterococci. IS256 has the capacity to influence expression of the ica operon and subsequent biofilm formation by reversible insertion into the ica operon and its regulatory genes as well as by chromosomal rearrangements (2,14,35,37). To investigate whether SCCmec cassettes and IS256 occur in specific STs, all isolates were tested for the presence of these genes.…”

Section: Resultsmentioning

confidence: 99%

“…The presence of multiple copies of IS256 in the ST27 genome might support this adaptation process by an ongoing generation of novel phenotypic and genotypic variants. Thus, involvement of IS256 in genome flexibility has been shown for the modulation of biofilm, resistance, and global regulatory gene expression (2,3,21,22,35,37). Therefore, the combination of biofilm formation, antibiotic resistance, and genetic flexibility may explain why ST27 has become the dominant ST within medical facilities.…”

Section: Discussionmentioning

confidence: 99%

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Clonal Analysis of Staphylococcus epidermidis Isolates Carrying or Lacking Biofilm-Mediating Genes by Multilocus Sequence Typing

et al. 2005

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Staphylococcus epidermidis is part of the normal microflora of the human skin but is also a leading cause of device-associated infections in critically ill patients. Commensal and clinical S. epidermidis isolates differ in their ability to form biofilms on medical devices; the synthesis of biofilms is mediated by the icaADBC operon. Currently, the epidemiological relatedness between ica-positive and -negative isolates is not known; neither is it known whether the ica genes can spread to biofilm-negative strains through horizontal gene transfer. In this study, multilocus sequence typing (MLST) was employed for the clonal analysis of 118 S. epidermidis icapositive and -negative strains. MLST revealed that the majority of ica-positive and -negative strains were closely related and formed a single clonal complex. Within this complex one sequence type (ST27) was identified which contained exclusively ica-positive isolates and represented the majority of clinical strains tested. ST27 and related ica-positive clones carried different SCCmec cassettes (conferring methicillin resistance) and the insertion sequence IS256. The findings suggest that the S. epidermidis infections analyzed in this report are mainly caused by a single clone (ST27) which occurs preferentially in hospitals and differs from clones in the community. It is hypothesized that the successful establishment of ST27 within nosocomial environments has been facilitated by the presence of genes encoding biofilm and resistance traits.Staphylococcus epidermidis is a bacterium that constitutes a major component of the normal skin and mucosal microfloras of humans. It is a leading cause of hospital-acquired infections, mostly associated with the use of medical devices in seriously ill or immunocompromised patients. Staphylococcus epidermidis pathogenesis relies on the ability of the bacteria to form thick multilayered biofilms on a wide variety of polymer and metal surfaces (12). In general, biofilms consist of bacteria embedded into a polysaccharide matrix which protects bacteria against hostile environments, including antibiotics and the action of the host immune system, and therefore are an important factor in the development of chronic and recurrent infections (13,30). Although the production of staphylococcal biofilm is dependent upon multiple regulatory proteins, an essential factor is the presence and expression of the four-gene icaADBC operon (15). The operon encodes enzymes necessary for production of polysaccharide intercellular adhesin (PIA), which is required for biofilm formation and is involved in hemagglutination and bacterial aggregation (7,19,20). In animal models, PIA-negative mutants were significantly less likely to cause catheter-associated infections than their PIA-positive isogenic counterparts (27). Epidemiological studies have clearly shown that the majority of commensal Staphylococcus epidermidis isolates lack the ica operon, whereas clinical strains obtained from device-associated infections harbor the genetic information for biofilm ...

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Clonal Analysis of Staphylococcus epidermidis Isolates Carrying or Lacking Biofilm-Mediating Genes by Multilocus Sequence Typing

et al. 2005

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“…Other research groups have shown that staphylococcal biofi lm formation is a highly variable factor, which is infl uenced by both regulatory processes and genetic mechanisms, such as phase variations, mutations, and chromosomal rearrangements [15][16][17][18]. The observation that some of these genetic processes are mediated by the action of insertion sequence (IS) elements prompted us to investigate the distribution of common staphylococcal IS elements among S. epidermidis strains of clinical and commensal origin.…”

Section: Introductionmentioning

confidence: 99%

Genetic determinants and biofilm formation of clinicalStaphylococcus epidermidisisolates from blood cultures and indwelling devises

Mertens¹,

Ghebremedhin²

2013

European Journal of Microbiology and Immunology

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For a long time, Staphylococcus epidermidis, as a member of the coagulase-negative staphylococci, was considered as part of the physiological skin flora of the human being with no pathogenic significance. Today, we know that S. epidermidis is one of the most prevalent causes for implant-associated and nosocomial infections. We performed pheno-and genotypic analysis (ica, IS256, SCCmec types, agr groups) of biofilm formation in 200 isolates. Fifty percent were genetically ica-positive and produced biofilm. Among all studied isolates, agr II and III and SCCmec type I were the most prevalent, whereas within the selected multi-resistant isolates (29%), agr I and III and SCCmec type II dominated. SCCmec type I and mecA-negative S. epidermidis isolates were associated with agr II. The majority of the blood culture and biopsy isolates were assigned to agr III and SCCmec type I, whereas agr II was predominantly detected in mecA-negative S. epidermidis isolated from catheter and implant materials. MLST analysis revealed the major clonal lineages of ST2, ST5, ST10, and ST242 (total 13 STs). ST2 isolates from blood cultures were icaA/D-positive and harbored SCCmec types II and III and IS256, whereas the icaA/D-and IS256-positive ST23 isolates were assigned to SCCmec types I and IV.

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“…Multiresistant S. epidermidis as well as Staphylococcus aureus are the most common causes of nosocomial infections associated with implanted biomaterials. In these clinical staphylococcal isolates IS256 proved to be highly active and caused a variety of genetic aberrations, such as reversible gene inactivations, DNA rearrangements, and large chromosomal deletions that affected the expression of virulence-and resistance-associated genes (12,(27)(28)(29)(30). Specifically, biofilm formation, which is one of the major factors in S. epidermidis pathogenesis, is influenced by IS256.…”

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Transposase-Dependent Formation of Circular IS256Derivatives inStaphylococcus epidermidisandStaphylococcus aureus

Loessner¹,

Dietrich²,

Dittrich³

et al. 2002

J Bacteriol

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IS256 is a highly active insertion sequence (IS) element of multiresistant staphylococci and enterococci. Here we show that, in a Staphylococcus epidermidis clinical isolate, as well as in recombinant Staphylococcus aureus and Escherichia coli carrying a single IS256 insertion on a plasmid, IS256 excises as an extrachromosomal circular DNA molecule. First, circles were identified that contained a complete copy of IS256. In this case, the sequence connecting the left and right ends of IS256 was derived from flanking DNA sequences of the parental genetic locus. Second, circle junctions were detected in which one end of IS256 was truncated. Nucleotide sequencing of circle junctions revealed that (i) either end of IS256 can attack the opposite terminus and (ii) the circle junctions vary significantly in size. Upon deletion of the IS256 open reading frame at the 3 end and site-directed mutageneses of the putative DDE motif, circular IS256 molecules were no longer detectable, which implicates the IS256-encoded transposase protein with the circularization of the element.IS256 is an insertion sequence (IS) element of staphylococci and enterococci that was originally identified as a bordering component of the composite aminoglycoside resistance-mediating transposon Tn4001 (2,8,9). IS256, together with 32 other elements, forms a family of ISs that also includes eukaryotic relatives (3). Information about IS256 is very limited (10), despite its wide distribution. Recently, it was demonstrated that the flanking IS256 copies of Tn4001 form tandem dimers and IS circles in an Escherichia coli genetic background (17). In previous studies we have been able to show that IS256 is associated with genetic rearrangements, causing phenotypic changes in its natural host Staphylococcus epidermidis. Multiresistant S. epidermidis as well as Staphylococcus aureus are the most common causes of nosocomial infections associated with implanted biomaterials. In these clinical staphylococcal isolates IS256 proved to be highly active and caused a variety of genetic aberrations, such as reversible gene inactivations, DNA rearrangements, and large chromosomal deletions that affected the expression of virulence-and resistance-associated genes (12,(27)(28)(29)(30). Specifically, biofilm formation, which is one of the major factors in S. epidermidis pathogenesis, is influenced by IS256. The element causes phase variation of biofilm expression in S. epidermidis by inactivation of the icaADBC operon, which encodes enzymes responsible for biofilm synthesis (28). Apparently, the icaC gene represents a hot spot for IS256 insertions. It was shown that the element creates 8-and 7-bp target site duplications during transposition (28; S. H. Cho and W. Ziebuhr, unpublished data). The spontaneous ica:: IS256 insertions are reversible and, accordingly, nucleotide sequencing of biofilm-forming revertants confirmed the precise excision of the element, including the initially duplicated target sequences. In these initial studies, however, the molecular mechanisms th...

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Chromosomal rearrangements affecting biofilm production and antibiotic resistance in a Staphylococcus epidermidis strain causing shunt-associated ventriculitis

Cited by 53 publications

References 23 publications

Clonal Analysis of Staphylococcus epidermidis Isolates Carrying or Lacking Biofilm-Mediating Genes by Multilocus Sequence Typing

Clonal Analysis of Staphylococcus epidermidis Isolates Carrying or Lacking Biofilm-Mediating Genes by Multilocus Sequence Typing

Genetic determinants and biofilm formation of clinicalStaphylococcus epidermidisisolates from blood cultures and indwelling devises

Transposase-Dependent Formation of Circular IS256Derivatives inStaphylococcus epidermidisandStaphylococcus aureus

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