Toxic triplets provide clues to neurodegeneration

Cleavage, aggregation and toxicity of the expanded androgen receptor in spinal and bulbar muscular atrophyMerry, D.E. et al. (1998)Hum. Mol. Genet. 7, 693–701Truncated N-terminal fragments of huntingtin with expanded glutamine repeats form nuclear and cytoplasmic aggregates in cell cultureCooper, J.K. et al. (1998)Hum. Mol. Genet. 7, 783–790Aggregation of N-terminal huntingtin is dependent on the length of its glutamine repeatsLi, S.H. and Li, X.J. (1998)Hum. Mol. Genet. 7, 777–782     

Stretching the boundaries of elastin function

Elastin is an essential determinant of arterial morphogenesisLi, D.Y. et al. (1998)Nature 393, 276–280An elastin gene mutation producing abnormal tropoelastin and abnormal elastic fibres in a patient with autosomal dominant cutis laxaTassabehji, M. et al. (1998)Hum. Mol. Genet. 7, 1021–1028     

Vaccine evasion by pneumococci: as easy as changing a cassette

Recombinational exchanges at the capsular polysaccharide biosynthetic locus lead to frequent serotype changes among natural isolates of Streptococcus pneumoniaeCoffey, T.J. et al. (1998)Mol. Microbiol. 27, 73–83     

A candidate gene for schizophrenia and bipolar disorder

Isolation of a novel potassium channel gene hSKCa3 containing a polymorphic CAG repeat: a candidate for schizophrenia and bipolar disorder?Chandy, K.G. et al. (1998)Mol. Psychiatr. 3, 32–37     

Transduction of Porcine Enteropathogenic Escherichia coli with a Derivative of a Shiga Toxin 2-Encoding Bacteriophage in a Porcine Ligated Ileal Loop System

In this study, we have investigated the ability of detoxified Shiga toxin (Stx)-converting bacteriophages Φ3538 (Δstx₂::cat) (H. Schmidt et al., Appl. Environ. Microbiol. 65:3855-3861, 1999) and H-19B::Tn10d-bla (D. W. Acheson et al., Infect. Immun. 66:4496-4498, 1998) to lysogenize enteropathogenic Escherichia coli (EPEC) strains in vivo. We were able to transduce the porcine EPEC strain 1390 (O45) with Φ3538 (Δstx₂::cat) in porcine ligated ileal loops but not the human EPEC prototype strain E2348/69 (O127). Neither strain 1390 nor strain E2348/69 was lysogenized under these in vivo conditions when E. coli K-12 containing H-19B::Tn10d-bla was used as the stx1 phage donor. The repeated success in the in vivo transduction of an Stx2-encoding phage to a porcine EPEC strain in pig loops was in contrast to failures in the in vitro trials with these and other EPEC strains. These results indicate that in vivo conditions are more effective for transduction of Stx2-encoding phages than in vitro conditions.     

Making an impression on X-linked mental retardation

Oligophrenin-1 encodes a rhoGAP protein involved in X-linked mental retardationBilluart, P. (1998)Nature 392, 923–926PAK3 mutation in nonsyndromic X-linked mental retardationAllen, K.M. et al. (1998)Nat. Genet. 20, 25–30Mutations in GDI1 are responsible for X-linked non-specific mental retardationD'Adamo, P. et al. (1998)Nat. Genet. 19, 134–139Non-specific X-linked semidominant mental retardation by mutations in a Rab GDP-dissociation inhibitorBienvenu, T. et al. (1998)Hum. Mol. Genet. 7, 1311–1315     

A reconstruction of the gene for ribulose bisphosphate carboxylase from Rhodospirillum rubrum that expresses the authentic enzyme in Escherichia coli

Escherichia coli plasmid pRR36, which expresses Rhodospirillum rubrum ribulose bisphosphate carboxylase/oxygenase (EC 4.1.1.39) as a fusion protein [Nargang et al., Mol. Gen. Genet. 193 (1984) 220–224], was used to construct a new clone of the carboxylase gene (rbc) whose expression product is the wild-type enzyme. This construction entailed removing all lacZ-coding sequences and a portion of the 5'-noncoding leader of the R. rubrum rbc gene. The highest specific activity of carboxylase was observed with an expression vector which juxtaposed the trp-lac (tac) hybrid promoter with the R. rubrum ribosome binding site and the rbc structural gene. The carboxylase expressed in E. coli JM107 was purified to near homogeneity and, based on subunit M_r and specific enzymic activity, the isolated protein appeared indistinguishable from authentic ribulose bisphosphate carboxylase from R. rubrum. N-terminal sequence analyses of the cloned enzyme verified that the cloned and wild-type enzymes are the same.     

A new type of tumour suppressor gene: a serine/threonine kinase joins the list

Peutz–Jeghers syndrome is caused by mutations in a novel serine threonine kinaseJenne, D.E. et al. (1998)Nat. Genet. 18, 38–43A serine/threonine kinase gene defective in Peutz–Jeghers syndromeHemminki, A. et al. (1998)Nature 391, 184–187     

Attraction and the single cell

Selective expression of the eotaxin receptor CCR3 by human T helper 2 cellsSallusto, F. et al. (1997)Science 277, 2005–2007Functional expression of the eotaxin receptor CCR3 in T lymphocytes co-localising with eosinophilsGerber, B.O. et al. (1997)Curr. Biol. 7, 836–843Differential expression of chemokine receptors and chemotactic responsiveness of type 1 T helper cells (Th1s) and Th2sBonecchi, R. et al. (1998)J. Exp. Med. 187, 129–134CCR5 is characteristic of Th1 lymphocytesLoetscher, M. et al. (1998)Nature 391, 344–345     

Identification of Potentially Diarrheagenic Atypical Enteropathogenic Escherichia coli Strains Present in Canadian Food Animals at Slaughter and in Retail Meats

This study identified and characterized enteropathogenic Escherichia coli (EPEC) in the Canadian food supply. Eighteen of 450 E. coli isolates from food animal sources were identified as atypical EPEC (aEPEC). Several of the aEPEC isolates identified in this study possessed multiple virulence genes, exhibited adherence and attaching and effacing (A/E) lesion formation, disrupted tight junctions, and were coclassified with the extraintestinal pathogenic E. coli (ExPEC) and enterotoxigenic E. coli (ETEC) pathotypes.     

New evidence for neuroprotection by estrogen

Estrogen reduces neuronal generation of Alzheimer β-amyloid peptidesXu, H. et al. (1998)Nat. Med. 4, 447–451Nuclear estrogen receptor-independent neuroprotection by estratrienes: a novel interaction with glutathioneGreen, P.S. et al. (1998)Neuroscience 84, 7–10     

Winning the war against antibiotic resistance

Antibiotic sensitization using biphenyl tetrazoles as potent inhibitors of Bacteroides fragilis metallo-β-lactamaseToney, J.H. et al. (1998)Chem. Biol. 5, 185–196Autoinducer of virulence as a target for vaccine and therapy against Staphylococcus aureusBalaban, N. et al. (1998)Science 280, 438–440     

Bacterial Macroscopic Rope-like Fibers with Cytopathic and Adhesive Properties

We present a body of ultrastructural, biochemical, and genetic evidence that demonstrates the oligomerization of virulence-associated autotransporter proteins EspC or EspP produced by deadly human pathogens enterohemorrhagic and enteropathogenic Escherichia coli into novel macroscopic rope-like structures (>1 cm long). The rope-like structures showed high aggregation and insolubility, stability to anionic detergents and high temperature, and binding to Congo Red and thioflavin T dyes. These are properties also exhibited by human amyloidogenic proteins. These macroscopic ropes were not observed in cultures of nonpathogenic Escherichia coli or isogenic espP or espC deletion mutants of enterohemorrhagic or enteropathogenic Escherichia coli but were produced by an Escherichia coli K-12 strain carrying a plasmid expressing espP. Purified recombinant EspP monomers were able to self-assemble into macroscopic ropes upon incubation, suggesting that no other protein was required for assembly. The ropes bound to and showed cytopathic effects on cultured epithelial cells, served as a substratum for bacterial adherence and biofilm formation, and protected bacteria from antimicrobial compounds. We hypothesize that these ropes play a biologically significant role in the survival and pathogenic scheme of these organisms.     

Bovine attaching and effacing Escherichia coli possess a pathogenesis island related to the LEE of the human enteropathogenic Escherichia coli strain E2348/69

Attaching and effacing Escherichia coli (AEEC) has been described as a cause of diarrhea in calves. The molecular pathogenesis of AEEC was mainly studied in human enteropathogenic E. coli strain E2348/69 in which the virulence correlated with the presence of a 35.4 kb pathogenesis island called LEE. We showed that several strains isolated from calves with diarrhea were able to produce attaching and effacing lesions in a rabbit ileal loop model and that they possess a pathogenesis island related to the LEE. Moreover, we showed that the LEE from bovine strains was inserted mainly at a different position in the chromosome compared to the human enteropathogenic E. coli strain E2348/69.     

Epidemic Enteropathogenic Escherichia Coli,Newfoundland, 1963: Autopsy Study of 16 Cases

The autopsy findings and certain other features are described in 16 fatal cases of infantile diarrhea associated with enteropathogenic Escherichia coli infection during the 1963 epidemic in Newfoundland which resulted in 100 deaths. Age is an important factor in the severity of the infection and in the outcome. Almost one-half the patients were under 4 months and a third under 2 months. Pathological changes in the gastrointestinal tract were meagre and were not pathognomonic. Other pathological findings and their possible role in the severity and fatal outcome in enteropathogenic Escherichia coli gastroenteritis are discussed. Such conditions as prematurity, congenital anomaly, trauma, neoplasm and metabolic disorders were, no doubt, also important factors in the outcome. Severe respiratory tract infection was the leading terminal cause of death. No sex, seasonal or geographic variation was found. Enteropathogenic Escherichia coli serotype 0111:B4 was the prevalent infecting organism.     

The Escherichia coli adherence factor plasmid of enteropathogenic Escherichia coli causes a global decrease in ubiquitylated host cell proteins by decreasing ubiquitin E1 enzyme expression through host aspartyl proteases

Ubiquitylation is a widespread post-translational global regulatory system that is essential for the proper functioning of various cellular events. Recent studies have shown that certain types of Escherichia coli can exploit specific aspects of the ubiquitylation system to influence downstream targets. Despite these findings, examination of the effects pathogenic E. coli have on the overall host ubiquitylation system remain unexplored. To study the impact that pathogenic E. coli have on the ubiquitylation levels of host proteins during infections, we analyzed the entire ubiquitylation system during enteropathogenic E. coli infections of cultured cells. We found that these microbes caused a dramatic decrease in ubiquitylated host proteins during these infections. This occurred with a concomitant reduction in the expression of essential E1 activating enzymes in the host, which are integral for the initiation of the ubiquitylation cascade. Control of host E1 enzyme levels was dependent on the E. coli adherence factor plasmid which acted on host aspartyl proteases within enteropathogenic E. coli. Hijacking of the ubiquitylation system did not require the plasmid-encoded regulator or bundle forming pilus expression, as enteropathogenic E. coli mutated in those factors did not revert the ubiquitylation of host proteins or the abundance of E1 enzyme proteins to uninfected levels. Our work shows that E. coli have developed strategies to usurp post-translational systems by targeting crucial enzymes. The ability of enteropathogenic E. coli to inactivate host protein ubiquitylation could enable more efficient effector protein functionality, providing increased bacterial control of host cells during enteropathogenic E. coli pathogenesis.     

Three New Species of Predatory Nematodes (Dorylaimida: Actinolaimoidea) from Korea

Three new species of predatory nematodes belonging to family Actinolaimidae, superfamily Actinolaimoidea, order Dorylaimida are described and illustrated. Westindicus sanaensis sp. n. has a body 1.9–2.4mm long; b = 3.7–4.3; c = 8.1–8.5; odontostyle 26.5–28.0μm long; spicules 71–74μm long; ventromedian supplements 15 and comes close to Westindicus cheongsongensis Choi et al, 1998 and Westindicus keralaensis Khan et al., 1994. Egtitus koriensis sp. n. is 1.8–2.0 mm long; b = 3.4–4.1; c = 14–18; odontostyle 20–21 μm, and comes close to Egtitus elaboratus (Cobb, 1906) Thorne, 1967; Egtitus itanagrus Khan et al., 1994 and Egtitus adhricus Khan & Jairajpuri, 1994. Stopractinca glandulus sp. n. is 2.3–2.4 mm long; b = 4.0–4.1; c = 11–12; odontostyle 26–28μm and differs from other two known species viz., Stopractincta orientalis Khan et al., 1994 and Stopractincta malnadensis Dhanam et al., 1994 in having very thick body cuticle and longer cardia, and in the presence of a gland at the base of oesophagus.     

Biofilm Modifies Expression of Ribonucleotide Reductase Genes in Escherichia coli

Ribonucleotide reductase (RNR) is an essential enzyme for all living organisms since is the responsible for the last step in the synthesis of the four deoxyribonucleotides (dNTPs) necessary for DNA replication and repair. In this work, we have investigated the expression of the three-RNR classes (Ia, Ib and III) during Escherichia coli biofilm formation. We show the temporal and spatial importance of class Ib and III RNRs during this process in two different E. coli wild-type strains, the commensal MG1655 and the enteropathogenic and virulent E2348/69, the prototype for the enteropathogenic E. coli (EPEC). We have established that class Ib RNR, so far considered cryptic, play and important role during biofilm formation. The implication of this RNR class under the specific growth conditions of biofilm formation is discussed.     

Cycle-specific replication of chromosomal and F-plasmid origins

There have been various proposals for the pattern of F-plasmid replication during the division cycle. Here we show that the recent studies of Gordon et al. (Cell 90, 1113–1121, 1997) on the duplication and segregation of green fluorescent protein (GFP) labeled replication origins of the Escherichia coli chromosome and the F plasmid during the division cycle support the proposal that the F plasmid replicates with a cell-cycle-specific (artiocyclic) pattern.     

Chemical modification studies on the tyrosyl-tRNA synthetase/tRNA complex are in agreement with an antico-operative binding scheme

Chemical modification experiments on the tyrosyl-tRNA synthetase/tRNA^tyr system of Bacillus stearothermophilus reported by Bosshard et al. (1975,1978) which have been interpreted in terms of a binding scheme with one binding site that spans two subunits have been re-evaluated by a more rigorous procedure. The results show that the experiments of Bosshard et al. are in agreement with the antico-operative binding model that has been demonstrated for the Escherichia coli system.