Molecular characterization of blaNDM-1 in an Acinetobacter baumannii strain isolated in Germany in 2007

Pfeifer, Yvonne; Wilharm, Gottfried; Zander, Esther; Wichelhaus, Thomas A.; Göttig, Stefan; Hunfeld, Klaus-Peter; Seifert, Harald; Witte, Wolfgang; Higgins, Paul G.

doi:10.1093/jac/dkr256

Cited by 180 publications

(156 citation statements)

References 19 publications

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“…Mussi et al (2005) have proved that ISAba125 causes insertional inactivation of the CarO OMP in A. baumannii strains, leading to a carbapenem-resistant profile. The insertion element ISAba125, first identified in A. baumannii, is widely distributed and has also been associated with gene variants of the bla NDM carbapenemase in the family Enterobacteriaceae (Hornsey et al, 2011;Nordmann et al, 2012;Pfeifer et al, 2011). The results obtained in this study show that IS elements such as ISAba125 could modulate antibiotic resistance depending on the antibiotic treatment of the patient as the isolates used in this study were of clinical origin.…”

Section: Discussionmentioning

confidence: 65%

Role of ISAba1 and ISAba125 in governing the expression of bla ADC in clinically relevant Acinetobacter baumannii strains resistant to cephalosporins

Lopes

Amyes

2012

Journal of Medical Microbiology

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Acinetobacter baumannii is a multi-resistant opportunistic nosocomial pathogen responsible for several outbreaks worldwide. It can cause several infections at various sites of the body. One of the main infections caused by this bacterium is ventilator-associated pneumonia in patients in intensive care units. Treating these infections is becoming difficult because of the high resistance to antimicrobial agents. This study compared the expression of the chromosomally encoded bla ADC gene in isolates having ISAba1, ISAba125 and no insertion upstream of the bla ADC gene in A. baumannii clinical isolates. It showed that the expression of bla ADC was six times greater when ISAba125 was present upstream of the gene in comparison with the constitutively expressed bla ADC gene with no insertion present upstream. The study indicated that ISAba125 has better promoters than ISAba1 and this is responsible for the overexpression of the bla ADC gene as they share considerable homology to the well-established Escherichia coli promoters. The "10 box of ISAba125 formed a fusion promoter with the "35 box of the bla ADC gene causing the bla ADC gene to be significantly overexpressed. The ability to upregulate the expression of bla ADC with the assistance of different insertion elements such as ISAba1 and ISAba125 has become an important factor in A. baumannii resistance to cephalosporins. INTRODUCTIONThe predominant mechanism of b-lactam resistance in Gram-negative bacteria is the synthesis of b-lactamases (Philippon et al., 2002). Following the introduction of highly stable cephalosporins, the carbapenems and monobactams, resistance initially appeared in organisms such as Enterobacter cloacae, Citrobacter freundii, Serratia marcescens and Pseudomonas aeruginosa, where mutations in the chromosome lead to the overproduction of the AmpC blactamase. This confers resistance to oxyimino-and 7-alphamethoxy-cephalosporins and monobactams (Sanders, 1987). Class C b-lactamases produced by Gram-negative bacteria can hydrolyse many b-lactam antibiotics including the cephamycins and oxyimino-cephalosporins (Philippon et al., 2002;Sanders, 1987;Caroff et al., 2000). These enzymes can also hydrolyse monobactams, such as aztreonam, to a lesser extent (Bush et al., 1995;Mammeri & Nordmann, 2007). Acinetobacter baumannii is a Gramnegative, non-fermenting coccobacillus, which is associated with serious nosocomial infections (Cisneros & Rodríguez-Baño, 2002;Levin et al., 2003). Antimicrobial treatment of such infections is difficult due to their multidrug resistance profile (Corvec et al., 2003). The AmpC enzyme from multiresistant A. baumannii was first sequenced from a Spanish isolate (Bou & Martínez-Beltrán, 2000). This constitutively expressed AmpC enzyme shares low similarity with Enterobacteriaceae AmpC cephalosporinases (Corvec et al., 2003). High-level expression of AmpC b-lactamase is a mechanism of chromosomally mediated resistance to cephalosporins in A. baumannii (Bou & Martínez-Beltrán, 2000). Transposable elements are important motors...

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Section: Discussionmentioning

confidence: 65%

Role of ISAba1 and ISAba125 in governing the expression of bla ADC in clinically relevant Acinetobacter baumannii strains resistant to cephalosporins

Lopes

Amyes

2012

Journal of Medical Microbiology

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“…This is particularly true with respect to genetic determinants conferring antibiotic resistance which have been presumably acquired in part from distinctly related species belonging to the Enterobacteriaceae and Pseudomonas (1). The apparent formation of so-called genetic exchange communities (46) is further illustrated by the recent finding that a potent resistance determinant, the New Delhi metallo-␤-lactamase 1 (NDM-1) first discovered in Klebsiella pneumoniae and Escherichia coli (47), probably originated in Acinetobacter (48) and can be transferred among A. baumannii isolates via natural transformation competence (49). Mechanistically, conjugative transfer can only partially explain the multitude of HGT events in Acinetobacter, given that tra and mob genes required for conjugative transfer are missing on most sequenced Acinetobacter plasmids (38).…”

Section: Discussionmentioning

confidence: 99%

DNA Uptake by the Nosocomial Pathogen Acinetobacter baumannii Occurs during Movement along Wet Surfaces

Wilharm¹,

Piesker²,

Laue³

et al. 2013

Journal of Bacteriology

107

165

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bThe emergence of Acinetobacter baumannii as an increasingly multidrug-resistant nosocomial pathogen largely relies on acquisition of resistance genes via horizontal gene transfer. Here, we demonstrate that many clinical isolates of A. baumannii take up DNA while they move along wet surfaces. We show that both motility and DNA uptake are abolished after inactivation of pilT, which putatively encodes the type 4 pilus (T4P) retraction ATPase, and comEC, which putatively encodes the DNA uptake channel, respectively. Inactivation of pilT correlates with an increase in the number and length of pili with an average diameter of 7.2 nm. In the Galleria mellonella infection model, the comEC mutant is significantly attenuated, whereas the pilT mutant is not, dissecting biologically distinct roles of T4P and the DNA uptake channel. Collectively, these findings promote our understanding of the mechanisms of DNA uptake and resistance development in A. baumannii, which may also apply to other important pathogens.

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“…Multidrug-resistant A. baumannii isolates are of great concern (5,6). In Acinetobacter spp., the bla NDM-1 gene is embedded in transposon Tn125 (4,7,8). Tn125 is a 10,099-bp composite transposon bracketed by two copies of the insertion sequence (IS) ISAba125 orientated in the same direction (Fig.…”

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confidence: 99%

Transposition of Tn 125 Encoding the NDM-1 Carbapenemase in Acinetobacter baumannii

Bontron

Nordmann

Poirel

2016

Antimicrob Agents Chemother

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The bla NDM-1 gene encodes a carbapenemase that confers resistance to almost all ␤-lactams, including last-resort carbapenems. This is increasingly reported worldwide in nosocomial and community-acquired Gram-negative bacteria. Acinetobacter baumannii is an important opportunistic pathogen that is considered an intermediate reservoir for the bla NDM-1 gene. In this species, the bla NDM-1 gene is located within the Tn125 composite transposon. The mechanism driving the mobility of Tn125 has not yet been elucidated. Here we experimentally demonstrated the transposition of Tn125 in A. baumannii. Systematic 3-bp duplication of the target site, being the signature of transposition, was evidenced. The target site consensus sequence for Tn125 transposition was found to be GC enriched at the duplicated 3 bp and AT rich in the vicinity. Transposition frequency was not influenced by temperature changes or by exposure to subinhibitory concentrations of various antibiotics. This work is the first direct evidence of the functionality of a composite transposon in A. baumannii. It provides a mechanistic clue for the dissemination of the bla NDM-1 gene in Acinetobacter spp. and subsequently among Enterobacteriaceae.

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Molecular characterization of blaNDM-1 in an Acinetobacter baumannii strain isolated in Germany in 2007

Abstract: Objectives To investigate the genetic environment of the metallo-β-lactamase gene bla

Cited by 180 publications

References 19 publications

Role of ISAba1 and ISAba125 in governing the expression of bla ADC in clinically relevant Acinetobacter baumannii strains resistant to cephalosporins

Role of ISAba1 and ISAba125 in governing the expression of bla ADC in clinically relevant Acinetobacter baumannii strains resistant to cephalosporins

DNA Uptake by the Nosocomial Pathogen Acinetobacter baumannii Occurs during Movement along Wet Surfaces

Transposition of Tn 125 Encoding the NDM-1 Carbapenemase in Acinetobacter baumannii

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