Genomic analysis and relatedness of P2-like phages of the Burkholderia cepacia complex

<p>Abstract</p> <p>Background</p> <p>The <it>Burkholderia cepacia </it>complex (BCC) is comprised of at least seventeen Gram-negative species that cause infections in cystic fibrosis patients. Because BCC bacteria are broadly antibiotic resistant, phage therapy is currently being investigated as a possible alternative treatment for these infections. The purpose of our study was to sequence and characterize three novel BCC-specific phages: KS5 (vB_BceM-KS5 or vB_BmuZ-ATCC 17616), KS14 (vB_BceM-KS14) and KL3 (vB_BamM-KL3 or vB_BceZ-CEP511).</p> <p>Results</p> <p>KS5, KS14 and KL3 are myoviruses with the A1 morphotype. The genomes of these phages are between 32317 and 40555 base pairs in length and are predicted to encode between 44 and 52 proteins. These phages have over 50% of their proteins in common with enterobacteria phage P2 and so can be classified as members of the <it>Peduovirinae </it>subfamily and the "P2-like viruses" genus. The BCC phage proteins similar to those encoded by P2 are predominantly structural components involved in virion morphogenesis. As prophages, KS5 and KL3 integrate into an AMP nucleosidase gene and a threonine tRNA gene, respectively. Unlike other P2-like viruses, the KS14 prophage is maintained as a plasmid. The P2 <it>E+E' </it>translational frameshift site is conserved among these three phages and so they are predicted to use frameshifting for expression of two of their tail proteins. The <it>lysBC </it>genes of KS14 and KL3 are similar to those of P2, but in KS5 the organization of these genes suggests that they may have been acquired via horizontal transfer from a phage similar to λ. KS5 contains two sequence elements that are unique among these three phages: an IS<it>Bmu</it>2-like insertion sequence and a reverse transcriptase gene. KL3 encodes an EcoRII-C endonuclease/methylase pair and Vsr endonuclease that are predicted to function during the lytic cycle to cleave non-self DNA, protect the phage genome and repair methylation-induced mutations.</p> <p>Conclusions</p> <p>KS5, KS14 and KL3 are the first BCC-specific phages to be identified as P2-like. As KS14 has previously been shown to be active against <it>Burkholderia cenocepacia in vivo</it>, genomic characterization of these phages is a crucial first step in the development of these and similar phages for clinical use against the BCC.</p

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Efficacy of rifampicin plus doxycycline versus rifampicin plus quinolone in the treatment of brucellosis

Objective: The aim of this study was to compare the efficacy, tolerability and side effects of 2 treatment regimens for brucellosis

Investigation of the antibiotic susceptibility patterns of pathogens causing nosocomial infections

Objective: The aim of this study is to determine the resistance patterns of bacteria causing nosocomial infections. The outcome of this resistance was followed for 3 years

Investigation of the antibiotic susceptibility patterns of pathogens causing nosocomial infections

WOS: 000224790700018PubMed ID: 15494811Objective: The aim of this study is to determine the resistance patterns of bacteria causing nosocomial infections. The outcome of this resistance was followed for 3 years. Methods: This study was carried out during 2000 to 2002 at a university hospital in Turkey. The resistance patterns of 570 bacteria (390 Gram-negative, 180 Gram-positive) against meropenem, imipenem, ceftazidime, cefotaxime, cefepime, piperacillin/tazobactam, ciprofloxacin and tobramycin were investigated using the E-test. Extended-spectrum beta-lactamase (ESBL) production was determined using ceftazidime and ceftazidime/clavulanic acid E-test strips. Results: Meropenem was the most effective antibiotic against Gram-negative organisms (89.0%); this was followed by imipenem (87.2%) and piperacillin/tazobactam (66.4%). The most active antibiotic against Gram-positive bacteria was imipenem (87.2%) and this was followed by piperacillin/tazobactam (81.7%) and meropenem (77.8%). The rates of production of ESBL by Escherichia coli were 20.9%, Klebsiella pneumoniae 50% and Serratia marcescens were 46.7%. Extended-spectrum beta-lactamase production increased each year (21.7%, 22.1% and 45.5%). All of the ESBL producing isolates were sensitive to meropenem and 98.5% sensitive to imipenem. AmpC beta-lactamase was produced by 20.9% of the Enterobacter species spp, Citrobacter spp. and Serratia marcescens. All of these were sensitive to meropenem and 77.8% to imipenem and ciprofloxacin. Multi-drug resistance rates in Acinetobacter spp were 45.4% and 37.7% in Pseudomonas aeruginosa isolates. Conclusion: As in the entire world, resistance to antibiotics is a serious problem in our country. Solving of this problem depends primarily on prevention of the development of resistance