Showing papers in "Annual Review of Microbiology in 2004"
TL;DR: Recent genetic, biochemical, and crystallographic studies have allowed substantial progress in describing molecular mechanisms of siderophore and hemophore interactions with the outer membrane receptors, transport through the inner membrane, iron storage, and regulation of genes encoding biosynthesis and uptake proteins.
Abstract: Iron is an essential element for most organisms, including bacteria. The oxidized form is insoluble, and the reduced form is highly toxic for most macromolecules and, in biological systems, is generally sequestrated by iron- and heme-carrier proteins. Thus, despite its abundance on earth, there is practically no free iron available for bacteria whatever biotope they colonize. To fulfill their iron needs, bacteria have multiple iron acquisition systems, reflecting the diversity of their potential biotopes. The iron/heme acquisition systems in bacteria have one of two general mechanisms. The first involves direct contact between the bacterium and the exogenous iron/heme sources. The second mechanism relies on molecules (siderophores and hemophores) synthesized and released by bacteria into the extracellular medium; these molecules scavenge iron or heme from various sources. Recent genetic, biochemical, and crystallographic studies have allowed substantial progress in describing molecular mechanisms of siderophore and hemophore interactions with the outer membrane receptors, transport through the inner membrane, iron storage, and regulation of genes encoding biosynthesis and uptake proteins.
984 citations
TL;DR: The recently described three-dimensional crystal structure of the cohesin-dockerin heterodimer sheds light on the critical amino acids that contribute to this high-affinity protein-protein interaction.
Abstract: The discrete multicomponent, multienzyme cellulosome complex of anaerobic cellulolytic bacteria provides enhanced synergistic activity among the different resident enzymes to efficiently hydrolyze intractable cellulosic and hemicellulosic substrates of the plant cell wall. A pivotal noncatalytic subunit called scaffoldin secures the various enzymatic subunits into the complex via the cohesin-dockerin interaction. The specificity characteristics and tenacious binding between the scaffoldin-based cohesin modules and the enzyme-borne dockerin domains dictate the supramolecular architecture of the cellulosome. The diversity in cellulosome architecture among the known cellulosome-producing bacteria is manifest in the arrangement of their genes in either multiple-scaffoldin or enzyme-linked clusters on the genome. The recently described three-dimensional crystal structure of the cohesin-dockerin heterodimer sheds light on the critical amino acids that contribute to this high-affinity protein-protein interaction. In addition, new information regarding the regulation of cellulosome-related genes, budding genetic tools, and emerging genomics of cellulosome-producing bacteria promises new insight into the assembly and consequences of the multienzyme complex.
883 citations
TL;DR: The most exhaustive searches have taken place in E. coli, resulting in identification of more than 50 small RNAs, or 1%-2% of the number of protein-coding genes.
Abstract: Small noncoding RNAs have been found in all organisms, primarily as regulators of translation and message stability. The most exhaustive searches have taken place in E. coli, resulting in identification of more than 50 small RNAs, or 1%-2% of the number of protein-coding genes. One large class of these small RNAs uses the RNA chaperone Hfq; members of this class act by pairing to target messenger RNAs. Among the members of this class are DsrA and RprA, which positively regulate rpoS translation, OxyS, which negatively regulates rpoS translation and fhlA translation, RyhB, which reapportions iron use in the cell by downregulating translation of many genes that encode Fe-containing proteins, and Spot 42, which changes the polarity of translation in the gal operon. The promoters of these small RNAs are tightly regulated, frequently as part of well-understood regulons. Lessons learned from the study of small RNAs in E. coli can be applied to finding these important regulators in other organisms.
601 citations
TL;DR: Because both anaerobic methane and ammonium oxidation have been separately and excellently reviewed elsewhere, the added value of reviewing these two processes in one place is explored.
Abstract: Anaerobic oxidation of methane and ammonium are two different processes catalyzed by completely unrelated microorganisms. Still, the two processes do have many interesting aspects in common. First, both of them were once deemed biochemically impossible and nonexistent in nature, but have now been identified as major factors in global carbon and nitrogen cycling. Second, the microorganisms responsible for both processes cannot be grown in pure culture yet; their detection and identification were based on molecular ecology, tracer studies, use of lipid biomarkers, and enrichment cultures. Third, these microorganisms grow extremely slowly (doubling time from weeks to months). Fourth, both processes have a good potential for application in biotechnology. Because both anaerobic methane and ammonium oxidation have been separately and excellently reviewed elsewhere, we focus on aspects of interest in the context of current developments in microbiology and explore the added value of reviewing these two processes in one place.
298 citations
TL;DR: This review covers both well-established and recent advances in the characterization of L. monocytogenes virulence determinants and their role in the pathophysiology of listeriosis.
Abstract: ▪ Abstract Listeria monocytogenes is the etiological agent of listeriosis, a severe human foodborne infection characterized by gastroenteritis, meningitis, encephalitis, abortions, and perinatal infections. This gram-positive bacterium is a facultative intracellular pathogen that induces its own uptake into nonphagocytic cells and spreads from cell to cell using an actin-based motility process. This review covers both well-established and recent advances in the characterization of L. monocytogenes virulence determinants and their role in the pathophysiology of listeriosis.
275 citations
TL;DR: The experimental evidence defining MAP as the cause of Johne's disease and the issues and controversies surrounding its potential pathogenic role in humans are discussed.
Abstract: Johne's disease is a chronic diarrhea affecting all ruminants. Mycobacterium avium subsp. paratuberculosis (MAP), a slowly growing mycobacteria, is the etiologic agent. There is also a concern that MAP might be a causative agent of some cases of inflammatory bowel disease in humans, especially Crohn's disease. Food products including pasteurized bovine milk have been suggested as potential sources of human infection. This review addresses microbial factors that may contribute to its pathogenicity. In addition, the experimental evidence defining MAP as the cause of Johne's disease and the issues and controversies surrounding its potential pathogenic role in humans are discussed.
252 citations
TL;DR: The viral dynamics involved in the formation of a quasispecies, the choice of mutagenic nucleoside analogs, and the studies that have demonstrated the feasibility of lethal mutagenesis are considered.
Abstract: Riboviruses and retroviruses have the highest rates of mutations of any known organism. Increasing the mutation rate of these viruses could exceed the error threshold for viability of a viral population within a host. Recent experiments with mutagenic nucleoside analogs validate this new approach to treating infection of RNA viruses. Lethal mutagenesis with HIV-infected cells in culture has been documented and has been postulated to be the mechanism for treatment of hepatitis C with ribavirin. We consider the viral dynamics involved in the formation of a quasispecies, the choice of mutagenic nucleoside analogs, and the studies that have demonstrated the feasibility of lethal mutagenesis.
225 citations
TL;DR: In this article, the authors consider the origin and fate of diversity in an explicitly ecological context and highlight the importance of environmental structure in governing the fate of the diversity and shed light on the genetic mechanisms generating diversity.
Abstract: ▪ Abstract Natural communities of microbes are often diverse, a fact that is difficult to reconcile with the action of natural selection in simple, uniform environments. We suggest that this apparent paradox may be resolved by considering the origin and fate of diversity in an explicitly ecological context. Here, we review insights into the ecological and genetic causes of diversity that stem from experiments with microbial populations evolving in the defined conditions of the laboratory environment. These studies highlight the importance of environmental structure in governing the fate of diversity and shed light on the genetic mechanisms generating diversity. We conclude by emphasizing the importance of placing detailed molecular-level studies within the context of a sound ecological and evolutionary framework.
220 citations
TL;DR: This review focuses on the recent advances in understanding mechanisms of protective immunity and why they fail in most infected individuals and the distinct yet complementary role of CD4+ and CD8+ T lymphocytes in this process.
Abstract: The hepatitis C virus (HCV) infects approximately three percent of the world's population. Some individuals resolve the infection spontaneously, but the majority develop persistent viremia that often causes progressive liver disease. There is an emerging consensus that cellular immune responses are essential for spontaneous resolution of acute hepatitis C and long-term protection from persistent infection. This review focuses on the recent advances in understanding mechanisms of protective immunity and why they fail in most infected individuals. The distinct yet complementary role of CD4+ and CD8+ T lymphocytes in this process is highlighted.
210 citations
TL;DR: Traveling waves, streams, and sporulation have increasing thresholds for C-signal activity, and this progression ensures that spores form inside fruiting bodies.
Abstract: Myxobacteria use soluble and cell-contact signals during their starvation-induced formation of fruiting bodies. These signals coordinate developmental gene expression with the cell movements that build fruiting bodies. Early in development, the quorum-sensing A-signal in Myxococcus xanthus helps to assess starvation and induce the first stage of aggregation. Later, the morphogenetic C-signal helps to pattern cell movement and shape the fruiting body. C-signal is a 17-kDa cell surface protein that signals by contact between the ends of two cells. The number of C-signal molecules per cell rises 100-fold from the beginning of fruiting body development to the end, when spores are formed. Traveling waves, streams, and sporulation have increasing thresholds for C-signal activity, and this progression ensures that spores form inside fruiting bodies.
208 citations
TL;DR: The understanding of Bartonella-host cell interactions and the molecular mechanisms of bacterial virulence and persistence are summarized and current controversies and unanswered questions are highlighted.
Abstract: The genus Bartonella comprises several important human pathogens that cause a wide range of clinical manifestations: cat-scratch disease, trench fever, Carrion's disease, bacteremia with fever, bacillary angiomatosis and peliosis, endocarditis, and neuroretinitis. Common features of bartonellae include transmission by blood-sucking arthropods and the specific interaction with endothelial cells and erythrocytes of their mammalian hosts. For each Bartonella species, the invasion and persistent intracellular colonization of erythrocytes are limited to a specific human or animal reservoir host. In contrast, endothelial cells are target host cells in probably all mammals, including humans. Bartonellae subvert multiple cellular functions of human endothelial cells, resulting in cell invasion, proinflammatory activation, suppression of apoptosis, and stimulation of proliferation, which may cumulate in vasoproliferative tumor growth. This review summarizes our understanding of Bartonella-host cell interactions and the molecular mechanisms of bacterial virulence and persistence. In addition, current controversies and unanswered questions in this area are highlighted.
TL;DR: The generality of the bacterial hypothesis of coral bleaching is discussed and several of the virulence factors, such as adhesin, toxin, and superoxide dismutase, are produced only at the elevated summer seawater temperatures.
Abstract: ▪ Abstract The scleractinian coral Oculina patagonica undergoes bleaching (loss of its endosymbiotic zooxanthellae) every summer in the eastern Mediterranean Sea when seawater temperatures rise. The causative agent of the disease is Vibrio shiloi. The pathogen adheres to a β-galactoside-containing receptor in the coral mucus, penetrates into epithelial cells, differentiates into a viable-but-not-culturable form, multiplies, and produces a proline-rich peptide toxin that inhibits photosynthesis of the zooxanthellae in the presence of ammonia. Several of the virulence factors, such as adhesin, toxin, and superoxide dismutase, are produced only at the elevated summer seawater temperatures. The fireworm Hermodice carunculata is a winter reservoir and spring/summer vector for V. shiloi. The generality of the bacterial hypothesis of coral bleaching is discussed.
TL;DR: The Antarctic continent harbors a range of specialized and sometimes highly localized microbial biotopes, and the consequences of some direct human impacts, such as physical disruption of microbial soil communities, are obvious if not yet quantitated.
Abstract: The Antarctic continent harbors a range of specialized and sometimes highly localized microbial biotopes. These include biotopes associated with desiccated mineral soils, rich ornithogenic soils, glacial and sea ice, ice-covered lakes, translucent rocks, and geothermally heated soils. All are characterized by the imposition of one or more environmental extremes (including low temperature, wide temperature fluctuations, desiccation, hypersalinity, high periodic radiation fluxes, and low nutrient status). As our understanding of the true microbial diversity in these biotopes expands from the application of molecular phylogenetic methods, we come closer to the point where we can make an accurate assessment of the impacts of environmental change, human intervention, and other natural and unnatural impositions. At present, it is possible to make reasonable predictions about the physical effects of local climate change, but only general predictions on possible changes in microbial community structure. The consequences of some direct human impacts, such as physical disruption of microbial soil communities, are obvious if not yet quantitated. Others, such as the dissemination of nonindigenous microorganisms into indigenous microbial communities, are not yet understood.
TL;DR: The most recent findings on the transcriptional regulatory system in fungi that enables genes to be expressed only when the ambient pH is conducive to their ultimate functions are discussed.
Abstract: All microorganisms must adapt to the pH of their environment. One aspect of this adaptation, particularly important for organisms that grow over a wide pH range, is the ability to express appropriately genes whose roles ultimately involve functions at the cell surface or in the environment. Genes encoding permeases, secreted enzymes, enzymes involved in synthesis of exported metabolites such as toxins and antibiotics, and probably enzymes modifying secreted proteins posttranslationally all fall into this category. Here we discuss the most recent findings on the transcriptional regulatory system in fungi that enables such genes to be expressed only when the ambient pH is conducive to their ultimate functions. The intriguing issue of how pH is sensed and how the resulting signal is transmitted to the transcription factor involves at least one late endosome component. Proper functioning of the regulatory system responding to ambient pH is essential for fungal pathogenicity of both animals and plants.
TL;DR: Subcutaneous inoculation of the HSV vectors can be used to transduce neurons of the dorsal root ganglion to provide a therapeutic effect in models of polyneuropathy and chronic regional pain, and human trials of nonreplicating HSV gene transfer by direct inoculation for treatment of glioblastoma and HSVGene transfer by subcutaneous vaccines for the treatment of chronic intractable pain should commence soon.
Abstract: Vectors constructed from recombinant herpes simplex virus (HSV) have special utility for gene transfer to the nervous system. Nonreplicating vectors created by deletion of essential immediate early genes can be propagated to high titers on complementing cell lines that provide the missing gene product(s) in trans. Direct inoculation of these vectors into neural parenchyma is effective in rodent models of brain tumor, Parkinson disease, spinal cord injury, and spinal root trauma. Subcutaneous inoculation of the HSV vectors can be used to transduce neurons of the dorsal root ganglion to provide a therapeutic effect in models of polyneuropathy and chronic regional pain. In human trials, direct injection of replication-competent HSV into brain tumors has proven safe. Human trials of nonreplicating HSV gene transfer by direct inoculation for treatment of glioblastoma and HSV gene transfer by subcutaneous inoculation for the treatment of chronic intractable pain should commence soon.
TL;DR: This review examines the influence of molecular investigation on lichenology during this first 15 years by examining the phylogenetic placement of the individual symbiotic partners with their free-living relatives, refining their nomenclature and classification.
Abstract: From the mid-1980s the symbionts in lichen associations, heterotrophic fungi and photosynthetic algae or cyanobacteria, were the subject of increasing numbers of molecular investigations Many of the studies examined the phylogenetic placement of the individual symbiotic partners with their free-living relatives, refining their nomenclature and classification Resulting phylogenies permitted the mapping of transitions to and from lichenization and stimulated discussion of the relative ease of gaining and losing symbiotic lifestyles Comparing symbiont phylogenies both rejected strict cospeciation and mirrored phylogenies and hinted at more complex forces of coevolution, including symbiont switching and selection Studies at the species and population levels examined patterns of species delimitation and geographic dispersion and processes such as gene flow, self-fertilization, and founder effect Significant genetic variation often was associated with mobile elements, group I and spliceosomal introns This review examines the influence of molecular investigation on lichenology during this first 15 years
TL;DR: New posttranscriptional features of the frq/white-collar oscillator (FWC) of Neurospora are described, including protein phosphorylation and degradation, dimerization, and complex formation.
Abstract: Recent advances in understanding circadian (daily) rhythms in the genera Neurospora, Gonyaulax, and Synechococcus are reviewed and new complexities in their circadian systems are described. The previous model, consisting of a unidirectional flow of information from input to oscillator to output, has now expanded to include multiple input pathways, multiple oscillators, multiple outputs; and feedback from oscillator to input and output to oscillator. New posttranscriptional features of the frq/white-collar oscillator (FWC) of Neurospora are described, including protein phosphorylation and degradation, dimerization, and complex formation. Experimental evidence is presented for frq-less oscillator(s) (FLO) downstream of the FWC. Mathematical models of the Neurospora system are also discussed.
TL;DR: Guided by ribosomal-RNA scaffold along an exact pattern, the rotatory motion results in stereochemistry that is optimal for peptide bond formation and for nascent protein entrance into the exit tunnel, the main target of antibiotics targeting ribosomes.
Abstract: ▪ Abstract High-resolution structures of ribosomal complexes revealed that minute amounts of clinically relevant antibiotics hamper protein biosynthesis by limiting ribosomal mobility or perturbing its elaborate architecture, designed for navigating and controlling peptide bond formation and continuous amino acid polymerization. To accomplish this, the ribosome contributes positional rather than chemical catalysis, provides remote interactions governing accurate substrate alignment within the flexible peptidyl-transferase center (PTC) pocket, and ensures nascent-protein chirality through spatial limitations. Peptide bond formation is concurrent with aminoacylated-tRNA 3′ end translocation and is performed by a rotatory motion around the axis of a sizable ribosomal symmetry-related region, which is located around the PTC in all known crystal structures. Guided by ribosomal-RNA scaffold along an exact pattern, the rotatory motion results in stereochemistry that is optimal for peptide bond formation and for ...
TL;DR: A structural analysis of designed and selected mutants of these enzymes has been undertaken and the results of this analysis are reviewed on the nonheme ferric iron intradiol dioxygenase protocatechuate 3,4-dioxy genase.
Abstract: The catechol dioxygenases allow a wide variety of bacteria to use aromatic compounds as carbon sources by catalyzing the key ring-opening step. These enzymes use specifically either catechol or protocatechuate (2,3-dihydroxybenozate) as their substrates; they use a bare metal ion as the sole cofactor. To learn how this family of metalloenzymes functions, a structural analysis of designed and selected mutants of these enzymes has been undertaken. Here we review the results of this analysis on the nonheme ferric iron intradiol dioxygenase protocatechuate 3,4-dioxygenase.
TL;DR: My professional life has been devoted to the study of microbial products and their biosynthesis, regulation, and overproduction, which has included primary metabolites and secondary metabolites.
Abstract: My professional life has been devoted to the study of microbial products and their biosynthesis, regulation, and overproduction These have included primary metabolites (glutamic acid, tryptophan, inosinic acid, guanylic acid, vitamin B(12), riboflavin, pantothenic acid, ethanol, and lactic acid) and secondary metabolites (penicillin, cephalosporins, streptomycin, fosfomycin, gramicidin S, rapamycin, indolmycin, microcin B17, fumagillin, mycotoxins, Monascus pigments, and tetramethylpyrazine) Other areas included microbial nutrition, strain improvement, bioconversions of statins and beta-lactams, sporulation and germination, plasmid stability, gel microdroplets, and the production of double-stranded RNA, the polymer xanthan, and enzymes (polygalacturonase, protease, cellulase) Most of the studies were carried out with me by devoted and hardworking industrial scientists for 15 years at Merck & Co and by similarly characterized students, postdoctorals, and visiting scientists during my 32 years at the Massachusetts Institute of Technology I owe much of my success to my mentors from academia and industry My recent research activities with undergraduate students at the Charles A Dana Research Institute for Scientists Emeriti (RISE) at Drew University have been very rewarding and are allowing me to continue my career