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Julian I. Rood

Bio: Julian I. Rood is an academic researcher from Monash University, Clayton campus. The author has contributed to research in topics: Clostridium perfringens & Plasmid. The author has an hindex of 69, co-authored 272 publications receiving 16922 citations. Previous affiliations of Julian I. Rood include Australian National University & Cornell University.


Papers
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Book
01 Jan 2006
TL;DR: The final three chapters deal with principles of safe practice, including the role of clinical cytology in patient management, medicolegal considerations, and the contentious issue of the relative merits of fine needle aspiration and core biopsy.
Abstract: specimen handling is emphasised but exact descriptions of smear preparation are not provided.) The final three chapters deal with principles of safe practice, including the role of clinical cytology in patient management, medicolegal considerations, and the contentious issue of the relative merits of fine needle aspiration and core biopsy. The intervening chapters are about specific areas of concern in practice, such as cystic lesions, lymphoid infiltrates and small round cell tumors. It should be apparent that I like this book very much, and it does succeed in its purpose of restating the potential and problems of clinical cytopathology in a way that provides both orientation for the neophyte and advice for the practicing pathologist. Having said that, there are occasional jarring things about it. An inexplicable number of spelling errors are present, including one on the first page! A few sub-standard photomicrographs appear to have been gleaned from other sources, and other photomicrographs seem to be a ‘‘poor fit’’ with the findings described in the text. But these are minor considerations. I intend to have trainees in my institution read the first few chapters several times during their time with the cytology service, and would certainly highly recommend this book to all practicing pathologists having any involvement with cytopathology.

867 citations

Journal ArticleDOI
TL;DR: The usage of the newer macrolides has increased dramatically over the last few years, which has led to increased exposure of bacterial populations to macrolide resistance, and the nomenclature for these genes has varied and has been inconsistent.
Abstract: Macrolides are composed of 14 (erythromycin and clarithromycin)-, 15 (azithromycin)-, or 16 (josamycin, spiramycin, and tylosin)-membered lactones to which are attached amino and/or neutral sugars via glycosidic bonds. Erythromycin was introduced in 1952 as the first macrolide antibiotic. Unfortunately, within a year, erythromycin-resistant (Emr) staphylococci from the United States, Europe, and Japan were described (101). Erythromycin is produced by Saccharopolyspora erythraea, while the newer macrolides are semisynthetic molecules with substitutions on the lactone. The newer derivatives, such as clarithromycin and azithromycin, have improved intracellular and tissue penetration, are more stable, are better absorbed, have a lower incidence of gastrointestinal side effects, and are less likely to interact with other drugs. They are useable against a wider range of infectious bacteria, such as Legionella, Chlamydia, Haemophilus, and some Mycobacterium species (not M. tuberculosis), and their pharmacokinetics provide for less frequent dosing than erythromycin (21, 47, 96, 97). As a result, the usage of the newer macrolides has increased dramatically over the last few years, which has led to increased exposure of bacterial populations to macrolides (101–103, 107). Macrolides inhibit protein synthesis by stimulating dissociation of the peptidyl-tRNA molecule from the ribosomes during elongation (101, 103). This results in chain termination and a reversible stoppage of protein synthesis. The first mechanism of macrolide resistance described was due to posttranscriptional modification of the 23S rRNA by the adenine-N6 methyltransferase (101–103). These enzymes add one or two methyl groups to a single adenine (A2058 in Escherichia coli) in the 23S rRNA moiety. Over the last 30 years, a number of adenine-N6-methyltransferases from different species, genera, and isolates have been described. In general, genes encoding these methylases have been designated erm (erythromycin ribosome methylation), although there are exceptions, especially in the antibiotic-producing organisms (see Tables ​Tables11 and ​and3)3) (103). As the number of erm genes described has grown, the nomenclature for these genes has varied and has been inconsistent (Table ​(Table1).1). In some cases, unrelated genes have been given the same letter designation, while in other cases, highly related genes (>90% identity) have been given different names. TABLE 1 rRNA methylase genes involved in MLSB resistance TABLE 3 Location of antibiotic resistance genesa The binding site in the 50S ribosomal subunit for erythromycin overlaps the binding site of the newer macrolides, as well as the structurally unrelated lincosamides and streptogramin B antibiotics. The modification by methylase(s) reduces the binding of all three classes of antibiotics, which results in resistance against macrolides, lincosamides, and streptogramin B antibiotics (MLSB). The rRNA methylases are the best studied among macrolide resistance mechanisms (47, 101–103). However, a variety of other mechanisms have been described which also confer resistance (Table ​(Table2).2). Many of these alternative mechanisms of resistance confer resistance to only one or two of the antibiotic classes of the MLSB complex. TABLE 2 Efflux and inactivating genes In this review, we suggest a new nomenclature for naming MLS genes and propose to use the rules developed for identifying and naming new tetracycline resistance genes (51, 52). This system, with a few recent modifications, was originally designed because of the ability of two genes to be distinguished uniquely by DNA-DNA probe methodology (51). It was generally found that two genes with <80% amino acid sequence identity provided enough variability in nucleotide sequence to permit distinct probes to be designed. Although many investigators are likely to sequence new genes, the use of probe technology allows rapid identification of isolates containing potentially new genes, as well as a reliable way to screen populations and determine the frequency of any one resistant determinant. Therefore, we continued this paradigm by assigning two genes of ≥80% amino acid identity to the same class and same letter designation, while two genes that show ≤79% amino acid identity are given a different letter designation. Table ​Table11 shows the results of the classification, with some classes having members with little variability, while others, like classes A and O, show a greater range of homology at both the DNA and amino acid levels. As new gene sequences emerge, ideally they will need to be compared by oligonucleotide probe hybridization and/or sequence analysis against the bank of known genes before a new designation is assigned. If multiple genes are available in any one class, especially when there is a range as in class A, then all representative members of the class should be examined, not just one. To confirm that the proposed name or number for the newly discovered resistance determinant has not been used by another investigator, please contact M. C. Roberts for this information. A similar request has been made for new tet genes (52).

846 citations

Journal ArticleDOI
30 Apr 2009-Nature
TL;DR: The construction of isogenic tcdA and tcdB mutants of a virulent C. difficile strain are described and their use in the hamster disease model is used to show that toxin B is a key virulence determinant.
Abstract: Clostridium difficile is the leading cause of infectious diarrhoea in hospitals worldwide, because of its virulence, spore-forming ability and persistence. C. difficile-associated diseases are induced by antibiotic treatment or disruption of the normal gastrointestinal flora. Recently, morbidity and mortality resulting from C. difficile-associated diseases have increased significantly due to changes in the virulence of the causative strains and antibiotic usage patterns. Since 2002, epidemic toxinotype III NAP1/027 strains, which produce high levels of the major virulence factors, toxin A and toxin B, have emerged. These toxins have 63% amino acid sequence similarity and are members of the large clostridial glucosylating toxin family, which are monoglucosyltransferases that are pro-inflammatory, cytotoxic and enterotoxic in the human colon. Inside host cells, both toxins catalyse the transfer of glucose onto the Rho family of GTPases, leading to cell death. However, the role of these toxins in the context of a C. difficile infection is unknown. Here we describe the construction of isogenic tcdA and tcdB (encoding toxin A and B, respectively) mutants of a virulent C. difficile strain and their use in the hamster disease model to show that toxin B is a key virulence determinant. Previous studies showed that purified toxin A alone can induce most of the pathology observed after infection of hamsters with C. difficile and that toxin B is not toxic in animals unless it is co-administered with toxin A, suggesting that the toxins act synergistically. Our work provides evidence that toxin B, not toxin A, is essential for virulence. Furthermore, it is clear that the importance of these toxins in the context of infection cannot be predicted exclusively from studies using purified toxins, reinforcing the importance of using the natural infection process to dissect the role of toxins in disease.

718 citations

Journal ArticleDOI
TL;DR: Data show unequivocally that in this isolate a functional NetB toxin is critical for the ability of C. perfringens to cause NE in chickens, and the netB mutant is the first rationally attenuated strain obtained in an NE-causing isolate ofC.
Abstract: For over 30 years a phospholipase C enzyme called alpha-toxin was thought to be the key virulence factor in necrotic enteritis caused by Clostridium perfringens. However, using a gene knockout mutant we have recently shown that alpha-toxin is not essential for pathogenesis. We have now discovered a key virulence determinant. A novel toxin (NetB) was identified in a C. perfringens strain isolated from a chicken suffering from necrotic enteritis (NE). The toxin displayed limited amino acid sequence similarity to several pore forming toxins including beta-toxin from C. perfringens (38% identity) and alpha-toxin from Staphylococcus aureus (31% identity). NetB was only identified in C. perfringens type A strains isolated from chickens suffering NE. Both purified native NetB and recombinant NetB displayed cytotoxic activity against the chicken leghorn male hepatoma cell line LMH; inducing cell rounding and lysis. To determine the role of NetB in NE a netB mutant of a virulent C. perfringens chicken isolate was constructed by homologous recombination, and its virulence assessed in a chicken disease model. The netB mutant was unable to cause disease whereas the wild-type parent strain and the netB mutant complemented with a wild-type netB gene caused significant levels of NE. These data show unequivocally that in this isolate a functional NetB toxin is critical for the ability of C. perfringens to cause NE in chickens. This novel toxin is the first definitive virulence factor to be identified in avian C. perfringens strains capable of causing NE. Furthermore, the netB mutant is the first rationally attenuated strain obtained in an NE-causing isolate of C. perfringens; as such it has considerable vaccine potential.

560 citations

Journal ArticleDOI
TL;DR: Now that it is possible to freely move genetic information back and forth between C. perfringens and Escherichia coli, it will be possible to apply modern molecular methods to studies on the pathogenesis of C. perfumeens infections.

428 citations


Cited by
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28 Jul 2005
TL;DR: PfPMP1)与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1(PfPMP1)与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员,通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

18,940 citations

01 Jun 2012
TL;DR: SPAdes as mentioned in this paper is a new assembler for both single-cell and standard (multicell) assembly, and demonstrate that it improves on the recently released E+V-SC assembler and on popular assemblers Velvet and SoapDeNovo (for multicell data).
Abstract: The lion's share of bacteria in various environments cannot be cloned in the laboratory and thus cannot be sequenced using existing technologies. A major goal of single-cell genomics is to complement gene-centric metagenomic data with whole-genome assemblies of uncultivated organisms. Assembly of single-cell data is challenging because of highly non-uniform read coverage as well as elevated levels of sequencing errors and chimeric reads. We describe SPAdes, a new assembler for both single-cell and standard (multicell) assembly, and demonstrate that it improves on the recently released E+V-SC assembler (specialized for single-cell data) and on popular assemblers Velvet and SoapDeNovo (for multicell data). SPAdes generates single-cell assemblies, providing information about genomes of uncultivatable bacteria that vastly exceeds what may be obtained via traditional metagenomics studies. SPAdes is available online ( http://bioinf.spbau.ru/spades ). It is distributed as open source software.

10,124 citations

Journal ArticleDOI
TL;DR: A concluding discussion identifies unresolved issues pertaining to microbial cellulose utilization, suggests approaches by which such issues might be resolved, and contrasts a microbially oriented cellulose hydrolysis paradigm to the more conventional enzymatically oriented paradigm in both fundamental and applied contexts.
Abstract: Fundamental features of microbial cellulose utilization are examined at successively higher levels of aggregation encompassing the structure and composition of cellulosic biomass, taxonomic diversity, cellulase enzyme systems, molecular biology of cellulase enzymes, physiology of cellulolytic microorganisms, ecological aspects of cellulase-degrading communities, and rate-limiting factors in nature. The methodological basis for studying microbial cellulose utilization is considered relative to quantification of cells and enzymes in the presence of solid substrates as well as apparatus and analysis for cellulose-grown continuous cultures. Quantitative description of cellulose hydrolysis is addressed with respect to adsorption of cellulase enzymes, rates of enzymatic hydrolysis, bioenergetics of microbial cellulose utilization, kinetics of microbial cellulose utilization, and contrasting features compared to soluble substrate kinetics. A biological perspective on processing cellulosic biomass is presented, including features of pretreated substrates and alternative process configurations. Organism development is considered for "consolidated bioprocessing" (CBP), in which the production of cellulolytic enzymes, hydrolysis of biomass, and fermentation of resulting sugars to desired products occur in one step. Two organism development strategies for CBP are examined: (i) improve product yield and tolerance in microorganisms able to utilize cellulose, or (ii) express a heterologous system for cellulose hydrolysis and utilization in microorganisms that exhibit high product yield and tolerance. A concluding discussion identifies unresolved issues pertaining to microbial cellulose utilization, suggests approaches by which such issues might be resolved, and contrasts a microbially oriented cellulose hydrolysis paradigm to the more conventional enzymatically oriented paradigm in both fundamental and applied contexts.

4,769 citations

Journal ArticleDOI
TL;DR: Changing the use of tetracyclines in human and animal health as well as in food production is needed if this class of broad-spectrum antimicrobials through the present century is to continue to be used.
Abstract: Tetracyclines were discovered in the 1940s and exhibited activity against a wide range of microorganisms including gram-positive and gram-negative bacteria, chlamydiae, mycoplasmas, rickettsiae, and protozoan parasites. They are inexpensive antibiotics, which have been used extensively in the prophlylaxis and therapy of human and animal infections and also at subtherapeutic levels in animal feed as growth promoters. The first tetracycline-resistant bacterium, Shigella dysenteriae, was isolated in 1953. Tetracycline resistance now occurs in an increasing number of pathogenic, opportunistic, and commensal bacteria. The presence of tetracycline-resistant pathogens limits the use of these agents in treatment of disease. Tetracycline resistance is often due to the acquisition of new genes, which code for energy-dependent efflux of tetracyclines or for a protein that protects bacterial ribosomes from the action of tetracyclines. Many of these genes are associated with mobile plasmids or transposons and can be distinguished from each other using molecular methods including DNA-DNA hybridization with oligonucleotide probes and DNA sequencing. A limited number of bacteria acquire resistance by mutations, which alter the permeability of the outer membrane porins and/or lipopolysaccharides in the outer membrane, change the regulation of innate efflux systems, or alter the 16S rRNA. New tetracycline derivatives are being examined, although their role in treatment is not clear. Changing the use of tetracyclines in human and animal health as well as in food production is needed if we are to continue to use this class of broad-spectrum antimicrobials through the present century.

3,647 citations

Journal ArticleDOI
TL;DR: The optimism of the early period of antimicrobial discovery has been tempered by the emergence of bacterial strains with resistance to these therapeutics, and today, clinically important bacteria are characterized not only by single drug resistance but also by multiple antibiotic resistance.
Abstract: The optimism of the early period of antimicrobial discovery has been tempered by the emergence of bacterial strains with resistance to these therapeutics. Today, clinically important bacteria are characterized not only by single drug resistance but also by multiple antibiotic resistance--the legacy of past decades of antimicrobial use and misuse. Drug resistance presents an ever-increasing global public health threat that involves all major microbial pathogens and antimicrobial drugs.

3,526 citations