OXA-46, a New Class D β-Lactamase of Narrow Substrate Specificity Encoded by a bla(VIM-1)-Containing Integron from a Pseudomonas aeruginosa Clinical Isolate

A novel OXA-type enzyme, named OXA-46, was found to be encoded by a gene cassette inserted into a class 1 integron from a multidrug-resistant Pseudomonas aeruginosa clinical isolate. The variable region of the integron also contained a bla(VIM-1) metallo-β-lactamase cassette and a duplicated aacA4 aminoglycoside acetyltransferase cassette. OXA-46 belongs to the OXA-2 lineage of class D β-lactamases. It exhibits 78% sequence identity with OXA-2 and the highest similarity (around 92% identity) with another OXA-type enzyme detected in clinical isolates of Burkholderia cepacia and in unidentified bacteria from a wastewater plant. Expression of bla(OXA-46) in Escherichia coli decreased susceptibility to penicillins and narrow-spectrum cephalosporins but not to extended-spectrum cephalosporins, cefsulodin, aztreonam, or carbapenems. The enzyme was overproduced in E. coli and purified by two anion-exchange chromatography steps (approximate yield, 6 mg/liter). OXA-46 was made of a 28.5-kDa polypeptide and exhibited an alkaline pI (7.8). In its native form OXA-46 appeared to be dimeric, and the oligomerization state was not affected by EDTA. Kinetic analysis of OXA-46 revealed a specificity for narrow-spectrum substrates, including oxacillin, other penicillins (but not temocillin), and narrow-spectrum cephalosporins. The enzyme apparently did not interact with temocillin, oxyimino-cephalosporins, or aztreonam. OXA-46 was inactivated by tazobactam and carbapenems and, although less efficiently, also by clavulanic acid. Enzyme activity was not affected either by EDTA or by divalent cations and exhibited low susceptibility to NaCl. These findings underscore the functional and structural diversity that can be encountered among class D β-lactamases

Novel 3-N-Aminoglycoside Acetyltransferase Gene, aac(3)-Ic, from a Pseudomonas aeruginosa Integron

A novel gene, aac(3)-Ic, encoding an AAC(3)-I aminoglycoside 3-N-acetyltransferase, was identified on a gene cassette inserted into a Pseudomonas aeruginosa integron that also carries a bla(VIM-2) and a cmlA7 gene cassette. The aac(3)-Ic gene product is 59 and 57% identical to AAC(3)-Ia and AAC(3)-Ib, respectively, and confers resistance to gentamicin and sisomicin

Structure of In31, a bla(IMP)-Containing Pseudomonas aeruginosa Integron Phyletically Related to In5, Which Carries an Unusual Array of Gene Cassettes

The location and environment of the acquired bla(IMP) gene, which encodes the IMP-1 metallo-β-lactamase, were investigated in a Japanese Pseudomonas aeruginosa clinical isolate (isolate 101/1477) that produced the enzyme. In this isolate, bla(IMP) was carried on a 36-kb plasmid, and similar to the identical alleles found in Serratia marcescens and Klebsiella pneumoniae clinical isolates, it was located on a mobile gene cassette inserted into an integron. The entire structure of this integron, named In31, was determined. In31 is a class 1 element belonging to the same group of defective transposon derivatives that originated from Tn402-like ancestors such as In0, In2, and In5. The general structure of In31 appeared to be most closely related to that of In5 from pSCH884, suggesting a recent common phylogeny for these two elements. In In31, the bla(IMP) cassette is the first of an array of five gene cassettes that also includes an aacA4 cassette and three original cassettes that have never been described in other integrons. The novel cassettes carry, respectively, (i) a new chloramphenicol acetyltransferase-encoding allele of the catB family, (ii) a qac allele encoding a new member of the small multidrug resistance family of proteins, and (iii) an open reading frame encoding a protein of unknown function. All the resistance genes carried on cassettes inserted in In31 were found to be functional in decreasing the in vitro susceptibilities of host strains to the corresponding antimicrobial agents

The Newborn's Reaction to Light as the Determinant of the Brain's Activation at Human Birth

Developmental neuroscience research has not yet fully unveiled the dynamics involved in human birth. The trigger of the first breath, often assumed to be the marker of human life, has not been characterized nor has the process entailing brain modification and activation at birth been clarified yet. To date, few researchers only have investigated the impact of the extrauterine environment, with its strong stimuli, on birth. This 'hypothesis and theory' article assumes the role of a specific stimulus activating the central nervous system (CNS) at human birth. This stimulus must have specific features though, such as novelty, efficacy, ubiquity, and immediacy. We propose light as a robust candidate for the CNS activation via the retina. Available data on fetal and neonatal neurodevelopment, in particular with reference to retinal light-responsive pathways, will be examined together with the GABA functional switch, and the subplate disappearance, which, at an experimental level, differentiate the neonatal brain from the fetal brain. In this study, we assume how a very rapid activation of retinal photoreceptors at birth initiates a sudden brain shift from the prenatal pattern of functions to the neonatal setup. Our assumption implies the presence of a photoreceptor capable of capturing and transducing light/photon stimulus, transforming it into an effective signal for the activation of new brain functions at birth. Opsin photoreception or, more specifically, melanopsin-dependent photoreception, which is provided by intrinsically photosensitive retinal ganglion cells (ipRGCs), is considered as a valid candidate. Although what is assumed herein cannot be verified in humans based on knowledge available so far, proposing an important and novel function can trigger a broad range of diversified research in different domains, from neurophysiology to neurology and psychiatry

Molecular Characterization of Integrons in Epidemiologically Unrelated Clinical Isolates of Acinetobacter baumannii from Italian Hospitals Reveals a Limited Diversity of Gene Cassette Arrays

Integron carriage by 36 epidemiologically unrelated Acinetobacter baumannii isolates collected over an 11-year period from patients in six different Italian hospitals was investigated. Sixteen type 1 integron-positive isolates (44%) were found, 13 of which carried the same array of cassettes, i.e., aacC1, orfX, orfX′, and aadA1a. As ribotype analysis of the isolates demonstrated a notable genetic diversity, horizontal transfer of the entire integron structure or ancient acquisition was hypothesized