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The Enterobacter cloacae complex (ECC) is highly diverse; its many species and subspecies can be distinguished by using phenotypic methods or matrix-assisted laser desorption/ionization time-offlight mass spectrometry. Whole-genome sequencing enables [...]

Few last-line antimicrobial agents effectively treat infections caused by New Delhi metallo-[beta]-lactamase (NDM)-producing Enterobacterales (1). Cefiderocol is a novel synthetic conjugate siderophore cephalosporin that is more stable against [beta]-lactamase hydrolysis [...]

The massive dissemination of carbapenemase-producing Enterobacterales poses a global threat to public health. Carbapenem antibiotics remain the last line of defense against highly resistant Enterobacterales. Carbapenemases have been identified in [...]

Severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) has spread globally and strained health systems with an exponentially increasing number of acute respiratory failures (1). Because severe cases of respiratory distress [...]

Carbapenems are the last line antimicrobial drugs for treating infections caused by multidrug-resistant Enterobacterales. The global dissemination of carbapenemase-producing Enterobacterales (CPE; formerly known as carbapenemase-producing Enterobacteriaceae) pose a serious threat [...]

In Klebsiella pneumoniae bacteria, resistance to carbapenems results in 2 main mechanisms: the production of an extended spectrum [beta]-lactamase or plasmid-borne cephalosporinase associated with a decrease in permeability of the [...]

In Europe, evidence for the spread of extended-spectrum [beta]-lactamase (ESBL)-producing Escherichia coli from animals to humans via food is unclear (1). Few studies have been conducted in low- and middle-income [...]

Enterobacteriaceae are inhabitants of the intestinal flora J-J and are among the most common human pathogens, causing infections such as cystitis and pyelonephritis with fever, septicemia, pneumonia, peritonitis, meningitis, and [...]

Resistance of Klebsiella pneumoniae to carbapenems is mainly associated with acquired carbapenem-hydrolyzing β-lactamases (1). These β-lactamases can be metallo β-lactamases (IMP, VIM), expanded-spectrum oxacillinases (OXA-48), or Ambler class A enzymes [...]

Acinetobacter baumannii is a gram-negative organism that is increasingly recognized as a major pathogen causing nosocomial infections, including bacteremia and ventilator-associated pneumonia, particularly in patients admitted to intensive care units [...]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/S1473-3099(09)70054-4 Byline: Patrice Nordmann (a), Gaelle Cuzon (a), Thierry Naas (a) Abstract: From early this decade, Enterobacteriaceae that produce Klebsiella pneumoniae carbapenemases (KPC) were reported in the USA and subsequently worldwide. These KPC-producing bacteria are predominantly involved in nosocomial and systemic infections; although they are mostly Enterobacteriaceae, they can also be, rarely, Pseudomonas aeruginosa isolates. KPC [beta] lactamases (KPC-1 to KPC-7) confer decreased susceptibility or resistance to virtually all [beta] lactams. Carbapenems (imipenem, meropenem, and ertapenem) may thus become inefficient for treating enterobacterial infections with KPC-producing bacteria, which are, in addition, resistant to many other non-[beta]-lactam molecules, leaving few available therapeutic options. Detection of KPC-producing bacteria may be difficult based on routine antibiotic susceptibility testing. It is therefore crucial to implement efficient infection control measures to limit the spread of these pathogens. Author Affiliation: (a) Service de Bacteriologie-Virologie-Hygiene, INSERM U914 'Emerging Resistance to Antibiotics', Hopital de Bicetre, Assistance Publique/Hopitaux de Paris, Faculte de Medecine and Universite Paris Sud, K -Bicetre, France

Ralstonia pickettii, an environmental bacterium that may also be responsible for human infections, produces two unrelated, inducible and chromosomally encoded oxacillinases, OXA-22 and OXA-60. In order to study the molecular basis of the induction process of these oxacillinase genes, the induction kinetics, the promoter/operator regions necessary for expression and induction, and the role of several ORFs located upstream and downstream of the [bla.su.b.OXA] genes were investigated. The [beta]-lactamase production reached a maximal level after 1 h induction, returned to its basal level within the following 3 h and was then again inducible. Using 5'RACE experiments, the promoter sequences of both oxacillinases were determined. These sequences showed weak promoter activities, which could, however, be increased approximately 200-fold by mutating the -35 promoter sequence. Deletion of the sequences located upstream of the promoter regions did not modify the basal [beta]-lactamase expression in R. pickettii, but resulted in the lack of induction. A minimum of 240 and 270 bp upstream of the transcription initiation sites was required for inducible expression of the [bla.sub.OXA-22] and [bla.sub.OXA-60] genes, respectively. Analysis of the genetic environment of both [bla.sub.OXA] genes revealed several ORFs that were inactivated by homologous recombination. Disruption of ORF-RP3, located 190 bp upstream of [bla.sub.OXA-60] and divergently transcribed, abolished induction of both [beta]-lactamases. ORF-RP3, which encoded a polypeptide of 532 aa with an estimated molecular mass of 58.7 kDa, displayed no obvious sequence homology with known regulatory proteins. Trans-complementation of ORF-RP3 restored the basal and inducible expression of both oxacillinase genes, indicating that the induction of both enzymes was related to the presence of ORF-RP3. In addition to the loss of induction, inactivation of the ORFRP3 in R. pickettii resulted in a complex pleiotropic phenotype, with increased lag phase and reduced survival after heat exposure, suggesting that ORF-RP3 might be a global regulator involved in unrelated regulatory pathways.

IS1999 and a point mutant derivative, IS1999.2, have been described inserted upstream of emerging antibiotic resistance genes [bla.sub.VEB-1] and [bla.sub.OXA-48]. 5' Rapid amplification of cDNA ends experiments revealed that expression of these [beta]-lactamase genes was driven by the outward-directed promoter, [P.sub.out], located in the IS1999 elements. These findings led us to study IS1999-mediated gene mobilization. Thus, the transposition properties of IS1999 and of IS1999-based composite transposons, made of two copies of IS1999 in different orientations, were investigated. IS1999 or IS1999-based composite transposons were capable of transposing onto the conjugative plasmid pOX38-Gen. Sequence analysis of the insertion sites revealed that IS1999 inserted preferentially into DNA targets containing the consensus sequence NGCNNNGCN. Transposition was more efficient when at least one left inverted repeat end was located at an outside end of the transposon. The transposition frequency of IS1999.2 was 10-fold lower than that of IS1999, and transposition frequencies of the putative natural transposon, Tn1999, were below detection limits of our transposition assay. This reduced transposition frequency of IS1999.2-based elements may result from a lower transcription of the transposase gene, as revealed by reverse transcription-PCR analyses.

VEB-1 extended-spectrum [beta]-lactamase-producing Acinetobacter baumannii was responsible for an outbreak in hospitals in France. A national alert was triggered in September 2003 when 4 hospitals reported clusters of A. baumannfi [...]

The integron-borne bl[a.sub.VEB-1] gene encodes an extended-spectrum [beta]-lactamase. This gene was associated mostly with IS1999 and rarely with an additional IS2000 element in Pseudomonas aeruginosa isolates from Thailand, whereas IS1999 was only very rarely associated with bl[a.sub.VEB.-1] in Enterobacteriaceae. Expression experiments and promoter study identified promoter sequences in IS1999 that increased the expression of VEB-1 in P.aeruginosa.

Research reveals that the plasmid-located class 1 integron In53 is a truncated integron and carries eight resistance gene cassette and is associated with the beta-lactamase gene environment in Escherichia coli. The integron is localized to the Tn2000 composite transposon and is bounded by two insertion sequence elements. In53 .

The high frequency autonomous retrotransposition of the human long interspersed nuclear elements (L1) L1.2 and LRE2in a cultured human cell line is demonstrated. The retrotransposed products resemble endogenous L1 insertions. Point mutations in conserved domains of L1.2-encoded proteins decreased retrotransposition by 100 to 1,000 times. L1.2 also retrotransposed in a mouse cell line, suggesting that L1-based vectors play a significant part in random insertional mutagenesis.

Hybridization studies of carbapenemase separated from the chromosome of a clinical isolate of Enterobacter cloacae NOR-1 reveal that the mature protein (NmcA) belongs to serine beta-lactamase class A. Amino acid sequence of NmcA exhibits similarity with the extended-spectrum class A beta-lactamase MEN-1 from Escherichia coli. Amino acid sequence of NmcR exhibits homology with the LysR-type transcriptional regulatory protein. Removal of NmcR reduces carbapenem resistance and loss of beta-lactamase inducibility, proving the vital function of NmcR in NmcA expression.

Genetic diversity, despite an extremely lowered rate of propagation during storage, was evident in bacterial subclones obtained from on old stab culture of Escherichia coli K-12. The examined insertion sequences (IS) influenced the genetic diversity. In several instances, IS transposition was responsible for this diversity which was due to IS5.

To the Editor: During the past decade, nosocomial infections due to multidrug-resistant Acinetobacter baumannii have been described with increasing frequency, mostly in intensive care units (ICUs), resulting in therapeutic difficulties [...]