1,721,259 research outputs found
Novel infectious diseases and emerging Gram-positive multi-resistant pathogens in hospital and community acquired infections
No full textReports on the emergence and prevalence of resistant bacterial infections in hospitals and communities raise concerns that we may soon no longer be able to rely on antibiotics as a way to control infectious diseases. Effective medical care would require the constant introduction of novel antibiotics to keep up in the "arms race" with resistant pathogens. This book closely examines the latest developments in the field of antibacterial research and development. It starts with an overview of the growing prevalence of resistant Gram-positive and Gram-negative pathogens, including their various resistance mechanisms, prevalence, risk factors and therapeutic options. The focus then shifts to a comprehensive description of all major chemical classes with antibacterial properties, their chemistry, mode of action, and the generation of analogs; information that provides the basis for the design of improved molecules to defeat microbial infections and combat the emerging resistances. In closing, recently developed compounds already in clinical use, those in preclinical or first clinical studies, and a number of promising targets to be exploited in the discovery stage are discussed
Gestione Diagnostico-Terapeutica del Paziente di Area Critica con Infezione Grave da Patogeni Batterici Multiresistenti
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Functional diversity among metallo-β-lactamases: characterization of the CAR-1 enzyme of Erwinia Carotovora
No full textMetallo-β-lactamases (MBLs) are zinc-dependent bacterial enzymes characterized by an efficient hydrolysis of carbapenems and a lack of sensitivity to commercially available β-lactamase inactivators. Apart from the acquired subclass B1 enzymes, which exhibit increasing clinical importance and whose evolutionary origin remains unclear, most MBLs are encoded by resident genes found in the genomes of organisms belonging to at least three distinct phyla. Using genome database mining, we identified an open reading frame (ORF) (ECA2849) encoding an MBL-like protein in the sequenced genome of Erwinia carotovora, an important plant pathogen. Although no detectable β-lactamase activity could be found in E. carotovora, a recombinant Escherichia coli strain in which the ECA2849 ORF was cloned showed decreased susceptibility to several β-lactams, while carbapenem MICs were surprisingly poorly affected. The enzyme, named CAR-1, was purified by means of ion-exchange chromatography steps, and its characterization revealed unique structural and functional features. This new MBL was able to efficiently hydrolyze cephalothin, cefuroxime, and cefotaxime and, to a lesser extent, penicillins and the other cephalosporins but only poorly hydrolyzed meropenem, while imipenem was not recognized. CAR-1 is the first example of a functional naturally occurring MBL in the family Enterobacteriaceae (order Enterobacteriales) and highlights the extraordinary structural and functional diversity exhibited by MBLs. Copyright © 2008, American Society for Microbiology. All Rights Reserved
Editorial: Exploiting Novel Combined Host- and Pathogen-Directed Therapies for Combating Bacterial Multidrug Resistance
Full text linkEditorial on the Research Topic "Exploiting Novel Combined Host- and Pathogen-Directed Therapies for Combating Bacterial
Multidrug Resistance
Genetic and biochemical characterization of FUS-1 (OXA-85), a narrow-spectrum class D beta-lactamase from Fusobacterium nucleatum subsp. polymorphum
No full textPrevious studies have reported β-lactamase-mediated penicillin resistance in Fusobacterium nucleatum, but no β-lactamase gene has yet been identified in this species. An F. nucleatum subsp. polymorphum strain resistant to penicillin and amoxicillin was isolated from a human periodontitis sample. DNA cloning and sequencing revealed a 765-bp open reading frame encoding a new class D β-lactamase named FUS-1 (OXA-85). A recombinant Escherichia coli strain carrying the blaFUS-1 gene exhibited resistance to amoxicillin with a moderate decrease in the MICs with clavulanic acid. The bla FUS-1 gene was found in two additional clonally unrelated F. nucleatum subsp. polymorphum isolates. It was located on the chromosome in a peculiar genetic environment where a gene encoding a putative transposase-like protein is found, suggesting a possible acquisition of this class D β-lactamase gene. The FUS-1 enzyme showed the closest ancestral relationship with OXA-63 from Brachyspira pilosicoli (53% identity) and with putative chromosomal β-lactamases of Campylobacter spp. (40 to 42% identity). FUS-1 presents all of the conserved structural motifs of class D β-lactamases. Kinetic analysis revealed that FUS-1 exhibits a narrow substrate profile, efficiently hydrolyzing benzylpenicillin and oxacillin. FUS-1 was poorly inactivated by clavulanate and NaC1. FUS-1 is the first example of a class D β-lactamase produced by a gram-negative, anaerobic, rod-shaped bacterium to be characterized. Copyright © 2006, American Society for Microbiology. All Rights Reserved
AmpC -lactamase-producing Enterobacterales: what a clinician should know
No full textBackgroundEnterobacterales are among the most common causes of bacterial infections in the community and among hospitalized patients, and multidrug-resistant (MDR) strains have emerged as a major threat to human health. Resistance to third-generation cephalosporins is typical of MDRs, being mainly due to the production of extended spectrum -lactamases or AmpC-type -lactamases.ObjectiveThe objective of this paper is to review the epidemiological impact, diagnostic issues and treatment options with AmpC producers.FindingsAmpC enzymes encoded by resident chromosomal genes (cAmpCs) are produced by some species (e.g., Enterobacter spp., Citrobacter freundii, Serratia marcescens), while plasmid-encoded AmpCs (pAmpCs) can be encountered also in species that normally do not produce cAmpCs (e.g., Salmonella enterica, Proteus mirabilis, Klebsiella pneumoniae and Klebsiella oxytoca) or produce them at negligible levels (e.g., Escherichia coli). Production of AmpCs can be either inducible or constitutive, resulting in different resistance phenotypes. Strains producing cAmpCs in an inducible manner (e.g., Enterobacter spp.) usually appear susceptible to third-generation cephalosporins, which are poor inducers, but can easily yield mutants constitutively producing the enzyme which are resistant to these drugs (which are good substrates), resulting in treatment failures. pAmpCs are usually constitutively expressed. Production of pAmpCs is common in community-acquired infections, while cAmpC producers are mainly involved in healthcare-associated infections.ConclusionsTo date, there is no conclusive evidence about the most appropriate treatment for AmpC-producing Enterobacterales. Carbapenems are often the preferred option, especially for severe infections in which adequate source control is not achieved, but cefepime is also supported by substantial clinical evidences as an effective carbapenem-sparing option
A NEW PLASMID CLONING VECTOR FOR DIRECT-DETECTION OF RECOMBINANT CLONES, BASED ON INACTIVATION OF A BACTERIAL ACID PHOSPHATASE-ENCODING GENE
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