Dataset Information

Translocation of Carbapenemase Gene blaKPC-2 both Internal and External to Transposons Occurs via Novel Structures of Tn1721 and Exhibits Distinct Movement Patterns.

ABSTRACT: The blaKPC-2 gene encodes a carbapenemase that hydrolyzes almost all ?-lactams, including carbapenems. The rapid emergence and international spread of this gene in Enterobacteriaceae seriously limit clinical treatment, posing an alarming threat for public health. Transposable elements, such as Tn4401, a proven transposon in Europe, the United States, and elsewhere, often play a role in the dissemination of the blaKPC-2 gene. In eastern China, the blaKPC-2 gene is frequently associated with several novel structures of Tn1721, but their transposition ability and mechanism of movement remain unclear. Here, we experimentally demonstrate that Tn1721-like transposons are capable of transferring blaKPC-2 both internal and external to the Tn1721 element from one strain to another and that distinct transposon structures exhibit different movement patterns and transposition frequencies. This process did not involve homologous recombination. Moreover, a 5-bp duplication of the target site, a characterized signature of transposition events in the Tn3 family, was confirmed. Tn1721-like transposons were found to insert preferentially into a 5-bp region that gradually exhibits a degenerated degree of AT-rich regions from both sides to the middle and that is immediately flanked by GC-rich regions. The observation in clinical isolates of diverse sequences flanking the transposons and a 5-bp duplication of the target site, as well as the prevalence of Tn1721-like transposons, also sustained our experimental results. This study first gives evidence about the functional role of Tn1721-like transposons in transferring the blaKPC-2 gene and provides new sight into the transposable element and the dissemination of antibiotic resistance in Enterobacteriaceae.

SUBMITTER: Tang Y

PROVIDER: S-EPMC5610484 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Translocation of Carbapenemase Gene blaKPC-2 both Internal and External to Transposons Occurs via Novel Structures of Tn1721 and Exhibits Distinct Movement Patterns.

Tang Yu Y Li Gang G Liang Wei W Shen Pinghua P Zhang Ying Y Jiang Xiaofei X

Antimicrobial agents and chemotherapy 20170922 10

The blaKPC-2 gene encodes a carbapenemase that hydrolyzes almost all β-lactams, including carbapenems. The rapid emergence and international spread of this gene in Enterobacteriaceae seriously limit clinical treatment, posing an alarming threat for public health. Transposable elements, such as Tn4401, a proven transposon in Europe, the United States, and elsewhere, often play a role in the dissemination of the blaKPC-2 gene. In eastern China, the ...[more]

PMID: 28784666

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Project description:The cell envelope of Gram-negative bacteria consists of two membranes surrounding the periplasm and peptidoglycan layer. β-Lactam antibiotics target the periplasmic penicillin-binding proteins that synthesize peptidoglycan, resulting in cell death. The primary means by which bacterial species resist the effects of β-lactam drugs is to populate the periplasmic space with β-lactamases. Resistance to β-lactam drugs is spread by lateral transfer of genes encoding β-lactamases from one species of bacteria to another. However, the resistance phenotype depends in turn on these "alien" protein sequences being recognized and exported across the cytoplasmic membrane by either the Sec or Tat protein translocation machinery of the new bacterial host. Here, we examine BKC-1, a carbapenemase from an unknown bacterial source that has been identified in a single clinical isolate of Klebsiella pneumoniae. BKC-1 was shown to be located in the periplasm, and functional in both K. pneumoniae and Escherichia coli. Sequence analysis revealed the presence of an unusual signal peptide with a twin arginine motif and a duplicated hydrophobic region. Biochemical assays showed this signal peptide directs BKC-1 for translocation by both Sec and Tat translocons. This is one of the few descriptions of a periplasmic protein that is functionally translocated by both export pathways in the same organism, and we suggest it represents a snapshot of evolution for a β-lactamase adapting to functionality in a new host. IMPORTANCE Bacteria can readily acquire plasmids via lateral gene transfer (LGT). These plasmids can carry genes for virulence and antimicrobial resistance (AMR). Of growing concern are LGT events that spread β-lactamases, particularly carbapenemases, and it is important to understand what limits this spread. This study provides insight into the sequence features of BKC-1 that exemplify the limitations on the successful biogenesis of β-lactamases, which is one factor limiting the spread of AMR phenotypes by LGT. With a very simple evolutionary adaptation, BKC-1 could become a more effective carbapenemase, underscoring the need to understand the evolution, adaptability, and functional assessment of newly reported β-lactamases rapidly and thoroughly.

Project description:Dual-task performance is often impaired after stroke. This may be resolved by enhancing patients' automaticity of movement. This study sets out to test the constrained action hypothesis, which holds that automaticity of movement is enhanced by triggering an external focus (on movement effects), rather than an internal focus (on movement execution). Thirty-nine individuals with chronic, unilateral stroke performed a one-leg-stepping task with both legs in single- and dual-task conditions. Attentional focus was manipulated with instructions. Motor performance (movement speed), movement automaticity (fluency of movement), and dual-task performance (dual-task costs) were assessed. The effects of focus on movement speed, single- and dual-task movement fluency, and dual-task costs were analysed with generalized estimating equations. Results showed that, overall, single-task performance was unaffected by focus (p = .341). Regarding movement fluency, no main effects of focus were found in single- or dual-task conditions (p's ≥ .13). However, focus by leg interactions suggested that an external focus reduced movement fluency of the paretic leg compared to an internal focus (single-task conditions: p = .068; dual-task conditions: p = .084). An external focus also tended to result in inferior dual-task performance (β = -2.38, p = .065). Finally, a near-significant interaction (β = 2.36, p = .055) suggested that dual-task performance was more constrained by patients' attentional capacity in external focus conditions. We conclude that, compared to an internal focus, an external focus did not result in more automated movements in chronic stroke patients. Contrary to expectations, trends were found for enhanced automaticity with an internal focus. These findings might be due to patients' strong preference to use an internal focus in daily life. Future work needs to establish the more permanent effects of learning with different attentional foci on re-automating motor control after stroke.

Dataset Information

Translocation of Carbapenemase Gene blaKPC-2 both Internal and External to Transposons Occurs via Novel Structures of Tn1721 and Exhibits Distinct Movement Patterns.

Publications

Translocation of Carbapenemase Gene <i>bla</i><sub>KPC-2</sub> both Internal and External to Transposons Occurs via Novel Structures of Tn<i>1721</i> and Exhibits Distinct Movement Patterns.

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