bluuebunny/crossref_metadata_2025_split huggingface dataset:
Global Regulation of
Staphylococcus aureus
Genes by Rot
Authors: Saïd-Salim B. , Dunman P. M. , McAleese F. M. , Macapagal D. , Murphy E. , McNamara P. J. , Arvidson S. , Foster T. J. , Projan S. J. , Kreiswirth B. N. 
Published: January 2003

ABSTRACT

Staphylococcus aureus
produces a wide array of cell surface and extracellular proteins involved in virulence. Expression of these virulence factors is tightly controlled by numerous regulatory loci, including
agr
,
sar
,
sigB
,
sae
, and
arl
, as well as by a number of proteins with homology to SarA. Rot (repressor of toxins), a SarA homologue, was previously identified in a library of transposon-induced mutants created in an
agr-
negative strain by screening for restored protease and alpha-toxin. To date, all of the SarA homologues have been shown to act as global regulators of virulence genes. Therefore, we investigated the extent of transcriptional regulation of staphylococcal genes by Rot. We compared the transcriptional profile of a
rot agr
double mutant to that of its
agr
parental strain by using custom-made Affymetrix GeneChips. Our findings indicate that Rot is not only a repressor but a global regulator with both positive and negative effects on the expression of
S. aureus
genes. Our data also indicate that Rot and
agr
have opposing effects on select target genes. These results provide further insight into the role of Rot in the regulatory cascade of
S. aureus
virulence gene expression.
A
cka-gfp
Transcriptional Fusion Reveals that the Colicin K Activity Gene Is Induced in Only 3 Percent of the Population
Authors: Mulec Janez , Podlesek Zdravko , Mrak Peter , Kopitar Andreja , Ihan Alojz , Žgur-Bertok Darja 
Published: January 2003

ABSTRACT

In prokaryotes, only a few examples of differential gene expression in cell populations have been described. Colicin production in natural populations of
Escherichia coli
, while providing a competitive advantage in the natural habitat, also leads to lysis of the toxin-producing cell. Colicin K synthesis has been found to be induced due to an increase in ppGpp (I. Kuhar, J. P. van Putten, D. Žgur-Bertok, W. Gaastra, and B. J. Jordi, Mol. Microbiol.
41:
207-216). Using two transcriptional fusions,
cka-gfp
and
cki-gfp
, we show that at the single-cell level, the colicin K activity gene
cka
is expressed in only 3% of the bacterial population upon induction by nutrient starvation. In contrast, the immunity gene
cki
is expressed in the large majority of the cells. Expression of the
cka-gfp
fusion in a
lexA
-defective strain and in a
relA spoT
mutant strain indicates that differential expression of
cka
is established primarily at the level of transcription.
Isolation of a Negative Control Mutant of the Nitrogen Assimilation Control Protein, NAC, in
Klebsiella aerogenes
Authors: Janes Brian K. , Rosario Christopher J. , Bender Robert A. 
Published: January 2003

ABSTRACT

A negative control mutant of the nitrogen assimilation control protein, NAC, has been isolated. Mutants with the leucine at position 111 changed to a nonhydrophobic residue activate transcription from
hut
and
ure
promoters, but fail to repress
gdhA
expression. This failure does not result from failure to bind to either of the two sites required for
gdhA
repression, but the binding at those sites is altered in the mutant. It appears that the NAC negative control mutants fail to form the complex structures (probably tetramers) formed by wild-type NAC at the
gdhA
promoter.
PIISignal Transduction Proteins, Pivotal Players in Microbial Nitrogen Control
Authors: Arcondéguy Tania , Jack Rachael , Merrick Mike 
Published: January 2003

SUMMARYThe PIIfamily of signal transduction proteins are among the most widely distributed signal proteins in the bacterial world. First identified in 1969 as a component of the glutamine synthetase regulatory apparatus, PIIproteins have since been recognized as playing a pivotal role in control of prokaryotic nitrogen metabolism. More recently, members of the family have been found in higher plants, where they also potentially play a role in nitrogen control. The PIIproteins can function in the regulation of both gene transcription, by modulating the activity of regulatory proteins, and the catalytic activity of enzymes involved in nitrogen metabolism. There is also emerging evidence that they may regulate the activity of proteins required for transport of nitrogen compounds into the cell. In this review we discuss the history of the PIIproteins, their structures and biochemistry, and their distribution and functions in prokaryotes. We survey data emerging from bacterial genome sequences and consider other likely or potential targets for control by PIIproteins.
Pneumococcal Virulence Factors: Structure and Function
Authors: Jedrzejas Mark J. 
Published: January 2003

SUMMARY
The overall goal for this review is to summarize the current body of knowledge about the structure and function of major known antigens of Streptococcus pneumoniae, a major gram-positive bacterial pathogen of humans. This information is then related to the role of these proteins in pneumococcal pathogenesis and in the development of new vaccines and/or other antimicrobial agents. S. pneumoniae is the most common cause of fatal community-acquired pneumonia in the elderly and is also one of the most common causes of middle ear infections and meningitis in children. The present vaccine for the pneumococcus consists of a mixture of 23 different capsular polysaccharides. While this vaccine is very effective in young adults, who are normally at low risk of serious disease, it is only about 60% effective in the elderly. In children younger than 2 years the vaccine is ineffective and is not recommended due to the inability of this age group to mount an antibody response to the pneumococcal polysaccharides. Antimicrobial drugs such as penicillin have diminished the risk from pneumococcal disease. Several pneumococcal proteins including pneumococcal surface proteins A and C, hyaluronate lyase, pneumolysin, autolysin, pneumococcal surface antigen A, choline binding protein A, and two neuraminidase enzymes are being investigated as potential vaccine or drug targets. Essentially all of these antigens have been or are being investigated on a structural level in addition to being characterized biochemically. Recently, three-dimensional structures for hyaluronate lyase and pneumococcal surface antigen A became available from X-ray crystallography determinations. Also, modeling studies based on biophysical measurements provided more information about the structures of pneumolysin and pneumococcal surface protein A. Structural and biochemical studies of these pneumococcal virulence factors have facilitated the development of novel antibiotics or protein antigen-based vaccines as an alternative to polysaccharide-based vaccines for the treatment of pneumococcal disease.
Tetracycline Antibiotics: Mode of Action, Applications, Molecular Biology, and Epidemiology of Bacterial Resistance
Authors: Chopra Ian , Roberts Marilyn 
Published: January 2003

SUMMARY
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.
Autophagy in Yeast: Mechanistic Insights and Physiological Function
Authors: Abeliovich Hagai , Klionsky Daniel J. 
Published: January 2003

SUMMARY
Unicellular eukaryotic organisms must be capable of rapid adaptation to changing environments. While such changes do not normally occur in the tissues of multicellular organisms, developmental and pathological changes in the environment of cells often require adaptation mechanisms not dissimilar from those found in simpler cells. Autophagy is a catabolic membrane-trafficking phenomenon that occurs in response to dramatic changes in the nutrients available to yeast cells, for example during starvation or after challenge with rapamycin, a macrolide antibiotic whose effects mimic starvation. Autophagy also occurs in animal cells that are serum starved or challenged with specific hormonal stimuli. In macroautophagy, the form of autophagy commonly observed, cytoplasmic material is sequestered in double-membrane vesicles called autophagosomes and is then delivered to a lytic compartment such as the yeast vacuole or mammalian lysosome. In this fashion, autophagy allows the degradation and recycling of a wide spectrum of biological macromolecules. While autophagy is induced only under specific conditions, salient mechanistic aspects of autophagy are functional in a constitutive fashion. In Saccharomyces cerevisiae, induction of autophagy subverts a constitutive membrane-trafficking mechanism called the cytoplasm-to-vacuole targeting pathway from a specific mode, in which it carries the resident vacuolar hydrolase, aminopeptidase I, to a nonspecific bulk mode in which significant amounts of cytoplasmic material are also sequestered and recycled in the vacuole. The general aim of this review is to focus on insights gained into the mechanism of autophagy in yeast and also to review our understanding of the physiological significance of autophagy in both yeast and higher organisms.
Secretory Pathway of Trypanosomatid Parasites
Authors: McConville Malcolm J. , Mullin Kylie A. , Ilgoutz Steven C. , Teasdale Rohan D. 
Published: January 2003

SUMMARYThe Trypanosomatidae comprise a large group of parasitic protozoa, some of which cause important diseases in humans. These include Trypanosoma brucei (the causative agent of African sleeping sickness and nagana in cattle), Trypanosoma cruzi (the causative agent of Chagas' disease in Central and South America), and Leishmania spp. (the causative agent of visceral and [muco]cutaneous leishmaniasis throughout the tropics and subtropics). The cell surfaces of these parasites are covered in complex protein- or carbohydrate-rich coats that are required for parasite survival and infectivity in their respective insect vectors and mammalian hosts. These molecules are assembled in the secretory pathway. Recent advances in the genetic manipulation of these parasites as well as progress with the parasite genome projects has greatly advanced our understanding of processes that underlie secretory transport in trypanosomatids. This article provides an overview of the organization of the trypanosomatid secretory pathway and connections that exist with endocytic organelles and multiple lytic and storage vacuoles. A number of the molecular components that are required for vesicular transport have been identified, as have some of the sorting signals that direct proteins to the cell surface or organelles in the endosome-vacuole system. Finally, the subcellular organization of the major glycosylation pathways in these parasites is reviewed. Studies on these highly divergent eukaryotes provide important insights into the molecular processes underlying secretory transport that arose very early in eukaryotic evolution. They also reveal unusual or novel aspects of secretory transport and protein glycosylation that may be exploited in developing new antiparasite drugs.
Regulation of Cellular Differentiation in Filamentous Cyanobacteria in Free-Living and Plant-Associated Symbiotic Growth States
Authors: Meeks John C. , Elhai Jeff 
Published: January 2003

SUMMARY
Certain filamentous nitrogen-fixing cyanobacteria generate signals that direct their own multicellular development. They also respond to signals from plants that initiate or modulate differentiation, leading to the establishment of a symbiotic association. An objective of this review is to describe the mechanisms by which free-living cyanobacteria regulate their development and then to consider how plants may exploit cyanobacterial physiology to achieve stable symbioses. Cyanobacteria that are capable of forming plant symbioses can differentiate into motile filaments called hormogonia and into specialized nitrogen-fixing cells called heterocysts. Plant signals exert both positive and negative regulatory control on hormogonium differentiation. Heterocyst differentiation is a highly regulated process, resulting in a regularly spaced pattern of heterocysts in the filament. The evidence is most consistent with the pattern arising in two stages. First, nitrogen limitation triggers a nonrandomly spaced cluster of cells (perhaps at a critical stage of their cell cycle) to initiate differentiation. Interactions between an inhibitory peptide exported by the differentiating cells and an activator protein within them causes one cell within each cluster to fully differentiate, yielding a single mature heterocyst. In symbiosis with plants, heterocyst frequencies are increased 3- to 10-fold because, we propose, either differentation is initiated at an increased number of sites or resolution of differentiating clusters is incomplete. The physiology of symbiotically associated cyanobacteria raises the prospect that heterocyst differentiation proceeds independently of the nitrogen status of a cell and depends instead on signals produced by the plant partner.
T Antigens of Simian Virus 40: Molecular Chaperones for Viral Replication and Tumorigenesis
Authors: Sullivan Christopher S. , Pipas James M. 
Published: January 2003

SUMMARYSimian virus 40 (SV40) is a small DNA tumor virus that has been extensively characterized due to its relatively simple genetic organization and the ease with which its genome is manipulated. The large and small tumor antigens (T antigens) are the major regulatory proteins encoded by SV40. Large T antigen is responsible for both viral and cellular transcriptional regulation, virion assembly, viral DNA replication, and alteration of the cell cycle. Deciphering how a single protein can perform such numerous and diverse functions has remained elusive. Recently it was established that the SV40 T antigens, including large T antigen, are molecular chaperones, each with a functioning DnaJ domain. The molecular chaperones were originally identified as bacterial genes essential for bacteriophage growth and have since been shown to be conserved in eukaryotes, participating in an array of both viral and cellular processes. This review discusses the mechanisms of DnaJ/Hsc70 interactions and how they are used by T antigen to control viral replication and tumorigenesis. The use of the DnaJ/Hsc70 system by SV40 and other viruses suggests an important role for these molecular chaperones in the regulation of the mammalian cell cycle and sheds light on the enigmatic SV40 T antigen—a most amazing molecule.
Microbial Methylation of Metalloids: Arsenic, Antimony, and Bismuth
Authors: Bentley Ronald , Chasteen Thomas G. 
Published: January 2003

SUMMARYA significant 19th century public health problem was that the inhabitants of many houses containing wallpaper decorated with green arsenical pigments experienced illness and death. The problem was caused by certain fungi that grew in the presence of inorganic arsenic to form a toxic, garlic-odored gas. The garlic odor was actually put to use in a very delicate microbiological test for arsenic. In 1933, the gas was shown to be trimethylarsine. It was not until 1971 that arsenic methylation by bacteria was demonstrated. Further research in biomethylation has been facilitated by the development of delicate techniques for the determination of arsenic species. As described in this review, many microorganisms (bacteria, fungi, and yeasts) and animals are now known to biomethylate arsenic, forming both volatile (e.g., methylarsines) and nonvolatile (e.g., methylarsonic acid and dimethylarsinic acid) compounds. The enzymatic mechanisms for this biomethylation are discussed. The microbial conversion of sodium arsenate to trimethylarsine proceeds by alternate reduction and methylation steps, with S-adenosylmethionine as the usual methyl donor. Thiols have important roles in the reductions. In anaerobic bacteria, methylcobalamin may be the donor. The other metalloid elements of the periodic table group 15, antimony and bismuth, also undergo biomethylation to some extent. Trimethylstibine formation by microorganisms is now well established, but this process apparently does not occur in animals. Formation of trimethylbismuth by microorganisms has been reported in a few cases. Microbial methylation plays important roles in the biogeochemical cycling of these metalloid elements and possibly in their detoxification. The wheel has come full circle, and public health considerations are again important.
Signal Transduction and Regulatory Mechanisms Involved in Control of the σS(RpoS) Subunit of RNA Polymerase
Authors: Hengge-Aronis Regine 
Published: January 2003

SUMMARYThe σS(RpoS) subunit of RNA polymerase is the master regulator of the general stress response in Escherichia coli and related bacteria. While rapidly growing cells contain very little σS, exposure to many different stress conditions results in rapid and strong σSinduction. Consequently, transcription of numerous σS-dependent genes is activated, many of which encode gene products with stress-protective functions. Multiple signal integration in the control of the cellular σSlevel is achieved by rpoS transcriptional and translational control as well as by regulated σSproteolysis, with various stress conditions differentially affecting these levels of σScontrol. Thus, a reduced growth rate results in increased rpoS transcription whereas high osmolarity, low temperature, acidic pH, and some late-log-phase signals stimulate the translation of already present rpoS mRNA. In addition, carbon starvation, high osmolarity, acidic pH, and high temperature result in stabilization of σS, which, under nonstress conditions, is degraded with a half-life of one to several minutes. Important cis-regulatory determinants as well as trans-acting regulatory factors involved at all levels of σSregulation have been identified. rpoS translation is controlled by several proteins (Hfq and HU) and small regulatory RNAs that probably affect the secondary structure of rpoS mRNA. For σSproteolysis, the response regulator RssB is essential. RssB is a specific direct σSrecognition factor, whose affinity for σSis modulated by phosphorylation of its receiver domain. RssB delivers σSto the ClpXP protease, where σSis unfolded and completely degraded. This review summarizes our current knowledge about the molecular functions and interactions of these components and tries to establish a framework for further research on the mode of multiple signal input into this complex regulatory system.
Critical Role of Human T-Lymphotropic Virus Type 1 Accessory Proteins in Viral Replication and Pathogenesis
Authors: Albrecht Björn , Lairmore Michael D. 
Published: January 2003

SUMMARY

Human T-cell lymphotropic virus type 1 (HTLV-1) infection is associated with a diverse range of lymphoproliferative and neurodegenerative diseases, yet pathogenic mechanisms induced by the virus remain obscure. This complex retrovirus contains typical structural and enzymatic genes but also unique regulatory and accessory genes in four open reading frames (ORFs) of the pX region of the viral genome (pX ORFs I to IV). The regulatory proteins encoded by pX ORFs III and IV, Tax and Rex, respectively, have been extensively characterized. In contrast the contribution of the four accessory proteins p12
I
, p27
I
, p13
II
, and p30
II
, encoded by pX ORFs I and II, to viral replication and pathogenesis remained unclear. Proviral clones that are mutated in either pX ORF I or II, while fully competent in cell culture, are severely limited in their replicative capacity in a rabbit model. Emerging evidence indicates that the HTLV-1 accessory proteins are critical for establishment of viral infectivity, enhance T-lymphocyte activation, and potentially alter gene transcription and mitochondrial function. HTLV-1 pX ORF I expression is critical to the viral infectivity in resting primary lymphocytes, suggesting a role for p12
I
in lymphocyte activation. The endoplasmic reticulum and cis-Golgi localizing p12
I
, encoded from pX ORF I, activates NFAT, a key T-cell transcription factor, through calcium-mediated signaling pathways and may lower the threshold of lymphocyte activation via the JAK/STAT pathway. In contrast p30
II
localizes to the nucleus and represses viral promoter activity, but may regulate cellular gene expression through p300/CBP or related coactivators of transcription. p13
II
targets mitochondrial proteins, where it alters the organelle morphology and may influence energy metabolism. Collectively, studies of the molecular functions of the HTLV-1 accessory proteins provide insight into strategies used by retroviruses that are associated with lymphoproliferative diseases.
Evolutionary Conservation of Reactions in Translation
Authors: Ganoza M. Clelia , Kiel Michael C. , Aoki Hiroyuki 
Published: January 2003

SUMMARYCurrent X-ray diffraction and cryoelectron microscopic data of ribosomes of eubacteria have shed considerable light on the molecular mechanisms of translation. Structural studies of the protein factors that activate ribosomes also point to many common features in the primary sequence and tertiary structure of these proteins. The reconstitution of the complex apparatus of translation has also revealed new information important to the mechanisms. Surprisingly, the latter approach has uncovered a number of proteins whose sequence and/or structure and function are conserved in all cells, indicating that the mechanisms are indeed conserved. The possible mechanisms of a new initiation factor and two elongation factors are discussed in this context.