The Prevalence of Sequences Homologous to IS256 in Clinical Enterococcal Isolates

Rice, Louis B.; Þórisdóttir, Anna Sesselja

doi:10.1006/plas.1994.1076

Cited by 30 publications

(22 citation statements)

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“…The presence of IS256 in two of the methicillin-resistant natural isolates was surprising, since this insertion sequence has not been detected before in S. sciuri isolates and our own data indicate that it is rarely carried by this species (I. Couto, unpublished data). Therefore, it seems reasonable to hypothesize that S. sciuri strains carrying IS256, in particular strain SS-37, which carries several copies of IS256, must have acquired this insertion sequence from an exogenous source, possibly from some human species of staphylococci (8,14) or other bacteria (18,19) known to carry multiple copies of IS256.…”

Section: Discussionmentioning

confidence: 99%

Development of Methicillin Resistance in Clinical Isolates of Staphylococcus sciuri by Transcriptional Activation of the mecA Homologue Native to the Species

Couto

Tomasz

et al. 2003

J Bacteriol

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The ␤-lactam resistance gene mecA was acquired by Staphylococcus aureus from an extraspecies source. The search for the possible origin of this gene has led to the identification of a close structural homologue of mecA as a native gene in the animal species Staphylococcus sciuri. Surprisingly, the overwhelming majority of S. sciuri isolates were fully susceptible to ␤-lactam antibiotics in spite of the ubiquitous presence of the mecA homologue in the bacteria. We now describe two unusual S. sciuri strains isolated from humans-SS-37 and SS-41-that showed resistance to methicillin associated with high rates of transcription of the mecA homologue and production of a protein resembling penicillin binding protein 2a, the gene product of S. aureus mecA. In strain SS-37 increased transcription of the mecA homologue was related to insertion of an IS256 element upstream of the structural gene, and strain SS-41 had single nucleotide alterations in the promoter region of the mecA homologue which appear to be related to up-regulation of the rate of transcription. A third methicillin-resistant human isolate of S. sciuri that carries both the native mecA homologue and a methicillin-resistant S. aureus (MRSA) type mecA, strain K3, was now shown to be unstable in the absence of drug selection, causing the segregation of antibiotic-susceptible cells accompanied by the loss of the MRSA type mecA. These observations illustrate the remarkable variety of strategies available to bacteria for acquiring mechanisms of drug resistance in the in vivo environment.The cellular mechanism of broad-spectrum ␤-lactam antibiotic resistance, by which Staphylococcus aureus and other staphylococcal species are capable of withstanding the inhibitory effects of all ␤-lactam antibiotics, including the semisynthetic ones such as methicillin, is based on acquisition of the mecA gene, the product of which is penicillin binding protein 2a (PBP2a), a protein with greatly reduced affinity to this class of antibiotics (10). The resistance mechanism conferred by mecA has been studied extensively not only because of the importance of resistant strains in the clinical setting but also because of the intriguing features of the mechanism itself, which still holds many unanswered questions. One such question is the origin of the mecA determinant, known for a long time to be exogenous to S. aureus and to other clinically relevant staphylococci (1,5,9). In a search for the possible original source of mecA, we identified a genetic element closely related to the S. aureus mecA gene in the animal commensal species Staphylococcus sciuri, which is one of the most abundant staphylococcal species on our planet (12) and is only distantly related to S. aureus along taxonomic lines (21, 24). The broad range of S. sciuri biochemical activities, including the ability to use inorganic nitrogen salts as the sole source of nitrogen, is usually considered the reason for the wide range of host organisms and habitats of this bacterium, which include the skins of several animals as we...

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Section: Discussionmentioning

confidence: 99%

Development of Methicillin Resistance in Clinical Isolates of Staphylococcus sciuri by Transcriptional Activation of the mecA Homologue Native to the Species

Couto

Tomasz

et al. 2003

J Bacteriol

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“…IS256 has been detected in the genome of several clinical isolates of enterococci and staphylococci (5,6), e.g., in the clinical methicillin-resistant S. aureus (MRSA) isolates of sequence type 228 (ST228) (1 copy), ST239 (8 to 21 copies), and ST247 (at least 14 copies) (7)(8)(9)(10)(11). The accumulation of multiple IS256 copies in the genomes is due to its transposition process, which is mediated by a copy-and-paste mechanism (12).…”

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confidence: 99%

Antibiotic-Induced Autoactivation of IS 256 in Staphylococcus aureus

Schreiber

Szekat

Josten

et al. 2013

Antimicrob Agents Chemother

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The 3= end of rsbU, encoding the positive regulator of the stress factor sigma B, was identified as a hot spot for spontaneous IS256 insertion in Staphylococcus aureus SA137/93G. Interestingly, subinhibitory concentrations of chloramphenicol in combination with heat stress, as well as linezolid and spectinomycin at physiological temperatures, selected for such rsbU:: IS256 insertion mutants. In consequence of the inactivation of rsbU, the IS256 transposition frequency was increased 4-fold in S. aureus HG001. Staphylococcus aureus is a major human pathogen and has been able to acquire resistance to nearly all clinically used antibiotics. Insertion sequences (IS elements) have been instrumental in the development of resistance, since they represent the active component of transposons and, thus, mobilize resistance genes for horizontal gene transfer (1) or modulate the expression of resistance-conferring genes (2). Therefore, investigation of the transposition process of IS elements, especially in the presence of subinhibitory concentrations of antibiotics, will help us to understand and ultimately, perhaps, interfere with resistance development.IS256 is a highly active insertion sequence that, as a component of the composite transposon Tn4001, has played a pivotal role in the development of aminoglycoside resistance in S. aureus (3, 4). IS256 has been detected in the genome of several clinical isolates of enterococci and staphylococci (5, 6), e.g., in the clinical methicillin-resistant S. aureus (MRSA) isolates of sequence type 228 (ST228) (1 copy), ST239 (8 to 21 copies), and ST247 (at least 14 copies) (7-11). The accumulation of multiple IS256 copies in the genomes is due to its transposition process, which is mediated by a copy-and-paste mechanism (12). The effect of multiple IS256 elements on genomic flexibility and resistance development is exemplified by S. aureus SA137/93G (more than 14 copies), an ST247 strain that displays homogeneous vancomycin-intermediate resistance (vancomycin-intermediate S. aureus [VISA] phenotype) (13), which is mainly caused by the insertion of IS256 into the tcaA gene (11,14). A variety of intrinsic and extrinsic mechanisms regulate the transposition activity of mobile elements in bacteria (15). Whereas subinhibitory concentrations of ciprofloxacin and vancomycin lead to the activation of IS256 transposition (16), the alternative sigma factor B, which controls the expression of genes involved in stress response (17), is a negative regulator of IS256 transposition in S. aureus (18). In the present study, we demonstrate that frequent insertion of IS256 into the rsbU gene, which encodes a positive regulator of SigB (19), resulted in the autoactivation of IS256 transposition in S. aureus. rsbU is a hot spot for spontaneous IS256 insertions. All strains, plasmids, and oligonucleotides are shown in Tables 1 and 2. Spontaneous insertion of IS256 into rsbU was first detected during attempts to integrate temperature-sensitive plasmids harboring a chloramphenicol resistance gene into the...

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“…Sequences homologous to IS256 are present in many strains of enterococci which express antibiotic resistance, including strains which do not express resistance to high levels of gentamicin (23,25). The presence of these elements in multiple copies raises the possibility that new IS256-based composite transposons will emerge.…”

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confidence: 99%

Tn5384, a composite enterococcal mobile element conferring resistance to erythromycin and gentamicin whose ends are directly repeated copies of IS256

Rice¹,

Carias²,

Marshall³

1995

Antimicrob Agents Chemother

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We have identified a 26-kb mobile element from Enterococcus faecalis CH116, designated Tn5384, which confers resistance to erythromycin and to high levels of gentamicin. Tn5384 is a composite element containing three copies of insertion element IS256. Two of the IS256 copies flank the aac6-aph2؆ bifunctional aminoglycoside-modifying-enzyme gene in the inverted orientation, forming a structure similar to staphylococcal gentamicin resistance transposon Tn4001. One of the IS256 elements involved in the Tn4001-like structure also forms the left end of Tn5384, the right end of which is a directly repeated insertion of IS256 approximately 23 kb downstream of the leftmost insertion. Insertions of Tn5384 into enterococcal plasmid pLRM1 have been found associated with 8-and 9-bp duplications of the target sequence.

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The Prevalence of Sequences Homologous to IS256 in Clinical Enterococcal Isolates

Cited by 30 publications

References 0 publications

Development of Methicillin Resistance in Clinical Isolates of Staphylococcus sciuri by Transcriptional Activation of the mecA Homologue Native to the Species

Development of Methicillin Resistance in Clinical Isolates of Staphylococcus sciuri by Transcriptional Activation of the mecA Homologue Native to the Species

Antibiotic-Induced Autoactivation of IS 256 in Staphylococcus aureus

Tn5384, a composite enterococcal mobile element conferring resistance to erythromycin and gentamicin whose ends are directly repeated copies of IS256

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