Bacterial pore-forming toxins: The (w)hole story?

Pore-forming toxins (PFTs) are the most common class of bacterial protein toxins and constitute important bacterial virulence factors. The mode of action of PFT is starting to be better understood. In contrast, little is known about the cellular response to this threat. Recent studies reveal that cells do not just swell and lyse, but are able to sense and react to pore formation, mount a defense, even repair the damaged membrane and thus survive. These responses involve a variety of signal-transduction pathways and sophisticated cellular mechanisms such as the pathway regulating lipid metabolism. In this review we discuss the different classes of bacterial PFTs and their modes of action, and provide examples of how the different bacteria use PFTs. Finally, we address the more recent field dealing with the eukaryotic cell response to PFT-induced damage. Received 19 September 2007; received after revision 18 October 2007; accepted 23 October 2007     

Lipopolysaccharide-binding molecules: transporters, blockers and sensors

Lipopolysaccharide (LPS), a major component of the outer membrane of Gram-negative bacteria, can be beneficial to the host by activating the innate immune system, or harmful, by inducing inflammation, disseminated intravascular coagulation, multiple organ failure, shock and often death. On the bacteria, and in host biological fluids and cells, LPS is never free but constantly attached to cognate-binding proteins. Understanding how LPS is transported and further recognized by sensors able to deliver a signal, or by inactivating molecules able to neutralize its biological effects, is an important goal. This review describes the large panel of peptides and proteins reported to associate with LPS, and provides information on their origin, their structure and the location of amino acid residues involved in their interaction with LPS. A better understanding of the mode of recognition of LPS by cognate proteins prompted many laboratories to design on a rational basis synthetic molecules which can be used to detect low amounts of endotoxin, or to act as efficient blockers of in vitro and in vivo responses to LPS.Received 15 January 2004; received after revision 20 February 2004; accepted 25 February 2004     

<Emphasis Type="Italic">Ascaris</Emphasis> nematodes from pig and human make three anti-bacterial peptides: isolation of cecropin P1 and two ASABF peptides

Organisms co-habiting with bacteria have developed efficient bactericidal agents to control their microbe-rich environment. The Ascaris nematode lives in its final development stages in the gut of its host and is believed to feed on bacteria. Ascaris suum survive in pig intestine while A. lumbricoides is the principal species in humans. Here we show that A. suum and A. lumbricoides both produce linear (cecropin P1) and cysteine-rich (ASABF) peptides with activity against either gram-negative or gram-positive bacteria, respectively. Thus nematodes rely in part on a peptide-based antibacterial system for digestion of bacteria, which may also confer protection against infection. Cecropin P1 was previously isolated from pig intestine but we can now conclude that was due to contaminating nematodes.     

Body size variability and water balance: A comparison between mainland and island populations ofMastomys huberti (Rodentia: Muridae) in Senegal

Generally rodents are found to be larger on islands than on the mainland. However, there are some exceptions to this rule, and the aim of this paper is to examine one of them. On the mainland of Senegal,Mastomys huberti occupies humid habitats. However, it occurs also on dry and sandy islands (Saloum delta), where its representatives are dwarf. Since water availability appeared to be the limiting factor in these islands when compared to the mainland, we studied water turnover characteristics in relation to body size, in mainland and island populations at the end of the dry season, under both field and laboratory conditions. All populations were found to be water balanced in their natural habitats. They presented similar rates of water turnover, even though island animals were subjected to stronger constraints than mainland ones. Laboratory experiments suggested that the physiological plasticity of one of the island populations may be reduced. Island populations have a higher kidney size to body weight ratio than those from the mainland. We propose that smaller size in the islands allows the maintenance of water balance with a smaller amount of water, and that a higher ratio of kidney filtration surface to body size may helpMastomys huberti to survive in dry islands. We discuss the factors responsible for body size variability and variation in water exchange characteristics and conclude that different factors could explain body size variation among island populations, depending on the species considered and the ecological constraints met within the islands.     

Natural killer cell activation by dendritic cells: balancing inhibitory and activating signals

Natural killer (NK) cells have originally been identified by their spontaneous cytolytic potential against tumor cells, which, however, might result from pre-activation due to prior pathogen exposure. Resting NK cells, on the contrary, require activation by bystander antigen-presenting cells to reach their full functional competence. In this review, we will summarize studies on how dendritic cells (DCs), the most potent type of antigen-presenting cell, communicate with human NK cells to activate them in secondary lymphoid organs and to integrate signals from activated NK cells at sites of inflammation for their own maturation. Furthermore, we will review aspects of the immunological synapse, which mediates this cross-talk. These studies provide the mechanistic understanding of how mature DCs can activate NK cells and survive to go on for the activation of adaptive immunity. This feature of DCs, to activate different waves of immune responses, could be harnessed for immunotherapies, including vaccinations.     

Human body temperature and new approaches to constructing temperature-sensitive bacterial vaccines

Many of the live human and animal vaccines that are currently in use are attenuated by virtue of their temperature-sensitive (TS) replication. These vaccines are able to function because they can take advantage of sites in mammalian bodies that are cooler than the core temperature, where TS vaccines fail to replicate. In this article, we discuss the distribution of temperature in the human body, and relate how the temperature differential can be exploited for designing and using TS vaccines. We also examine how one of the coolest organs of the body, the skin, contains antigen-processing cells that can be targeted to provoke the desired immune response from a TS vaccine. We describe traditional approaches to making TS vaccines, and highlight new information and technologies that are being used to create a new generation of engineered TS vaccines. We pay particular attention to the recently described technology of substituting essential genes from Arctic bacteria for their homologues in mammalian pathogens as a way of creating TS vaccines.     

The starvation-survival state of microorganisms in nature and its relationship to the bioavailable energy

Summary Although one can measure the organic matter in various ecosystems in terms of organic carbon, this measurement does not indicate what portion of the organic carbon is bioavailable to the microorganisms. Most organic matter is recalcitrant and, therefore, most microorganisms do not have sufficient energy to carry on their metabolism for growth and reproduction. As a result, many species of bacteria will form ultramicrocells and enter a physiological state known as starvation-survival. This physiological state results in metabolic arrest which permits the organisms to survive for long periods of time without sufficient energy for growth and reproduction.Technical paper No. 8920, Oregon Agricultural Experiment Station.     

An overview of RNAs with regulatory functions in gram-positive bacteria

During the last decade, RNA molecules with regulatory functions on gene expression have benefited from a renewed interest. In bacteria, recent high throughput computational and experimental approaches have led to the discovery that 10–20% of all genes code for RNAs with critical regulatory roles in metabolic, physiological and pathogenic processes. The trans-acting RNAs comprise the noncoding RNAs, RNAs with a short open reading frame and antisense RNAs. Many of these RNAs act through binding to their target mRNAs while others modulate protein activity or target DNA. The cis-acting RNAs include regulatory regions of mRNAs that can respond to various signals. These RNAs often provide the missing link between sensing changing conditions in the environment and fine-tuning the subsequent biological responses. Information on their various functions and modes of action has been well documented for gram-negative bacteria. Here, we summarize the current knowledge of regulatory RNAs in gram-positive bacteria.     

Heat shock proteins in autoimmune disease. From causative antigen to specific therapy?

Heat shock proteins (hsp) are highly conserved from bacteria to man. Bacterial hsp, with approximate molecular weights of 60 kDa (hsp60), are immunodominant antigens that are immunologically cross-reactive with their mammalian counterparts. Hsp molecules are therefore useful in studies of fundamental questions concerning immune responses to foreign as opposed to self antigens. The finding that immune responses to hsp are associated with both experimentally-induced and spontaneous autoimmune diseases in animals has prompted intensive research to assess the role of bacterial hsp as the etiological agents involved in the development of autoimmune diseases. Recent evidence from animal models of autoimmune disease has clearly demonstrated the involvement of hsp in both the pathogenesis and the immunoregulation of autoimmune diseases. Studies with arthritogenic and diabetogenic T cell clones have identified immunogenic epitopes of hsp. These have been shown to ameliorate adjuvant arthritis in Lewis rats, and insulin-dependent diabetes mellitus (IDDM) in non-obese diabetic (NOD) mice. Such studies may have important therapeutic implications for the future treatment of human autoimmune disease.     

Experimental evidence of the territorial defense,hypothesis in insular Blue Tits

Many insular vertebrates have unusually high population densities and are characterized by behavioural shifts including reduced territory size and reduced situation-specific aggressiveness. Compared to their mainland counterparts, Blue Tits on the island of Corsica exhibit many traits that fit the trends observed in crowded insular populations. We demonstrate from behavioural observations in aviaries and from hormone measurements that Corsican its are less aggressive than mainland ones. These shifts, as well as changes in reproductive patterns, support the defense hypothesis.     

Genetics of toxin production and resistance in phytopathogenic bacteria

Genes for phytotoxin production have been identified and cloned from several phytopathogenic pseudomonads. These genes comprise physically linked clusters that have been located both on the chromosome and on endogenous plasmids. Contained within these genetic regions are resistance genes specific to those toxins that have a bactericidal component to their activity. DNA sequences required for toxin production are often conserved among bacteria with divergent host specificities, suggesting the ability of toxin genes to be transferred between bacteria. Toxins are usually modulators of plant pathogenicity, their production causing a significant increase in disease severity. In one case, however, toxin production appears to be a major contributor to the basic pathogenicity of a plant pathogenic bacterium.     

Heat shock proteins in autoimmune disease. From causative antigen to specific therapy?

Heat shock proteins (hsp) are highly conserved from bacteria to man. Bacterial hsp, with approximate molecular weights of 60 kDa (hsp60), are immunodominant antigens that are immunologically cross-reactive with their mammalian counterparts. Hsp molecules are therefore useful in studies of fundamental questions concerning immune responses to foreign as opposed to self antigens. The finding that immune responses to hsp are associated with both experimentally-induced and spontaneous autoimmune diseases in animals has prompted intensive research to assess the role of bacterial hsp as the etiological agents involved in the development of autoimmune diseases. Recent evidence from animal models of autoimmune disease has clearly demonstrated the involvement of hsp in both the pathogenesis and the immunoregulation of autoimmune diseases. Studies with arthritogenic and diabetogenic T cell clones have identified immunogenic epitopes of hsp. These have been shown to ameliorate adjuvant arthritis in Lewis rats, and insulin-dependent diabetes mellitus (IDDM) in non-obese diabetic (NOD) mice. Such studies may have important therapeutic implications for the future treatment of human autoimmune disease.Dedicated to Professor Hermann A. Moser on the occasion of his 71st birthday.     

The peptidoglycan recognition proteins LCa and LCx

Infection of bacteria triggers innate immune defense reactions in Drosophila. So far, the only bacterial component known to be recognized by the insect innate immune system is peptidoglycan, one of the most abundant constituents of the bacterial cell wall. Insects use peptidoglycan recognition proteins to detect peptidoglycan and to activate innate immune responses. Such specialized peptidoglycan receptors appear to have evolved from phage enzymes that hydrolyze bacterial cell walls. They are able to bind specific peptidoglycan molecules with distinct chemical moieties and activate innate immune pathways by interacting with other signaling proteins. Recent X-ray crystallographic studies of the peptidoglycan recognition proteins LCa, and LCx bound to peptidoglycan have provided structural insights into recognition of peptidoglycan and activation of innate immunity in insects. Received 28 December 2006; received after revision 2 February 2007; accepted 21 February 2007     

The role of muscle in determining growth and size in teleost fish

Summary Rapid growth to large size in fish results from a sustained recruitment of new fibres into their axial series of myomeres. Cessation of recruitment at a small fish size leads to slow growth and a small final size of the fish. Fibre growth dynamics of fishes evidently govern growth and size through fibres' surface area to length ratios, which control their nutrient assimilation rates.     

Feeding in infancy: Short- and long-term effects on cardiovascular function

Cardiovascular responses of adult organisms to feeding are well characterized and, in general, are understood as acute adaptations required for processing and distributing nutrients. Research over the past several years has shown that infants also have important cardiovascular responses to nutrient intake and that these are regulated by changes in autonomic activity to the heart and vasculature. Recent studies have provided results that suggest these responses in infancy may make an important contribution to the long-term development of cardiovascular function, in particular, adult blood pressure (BP). The purpose of this presentation will be to review the evidence that has led to this conclusion, offer ideas about how this potential early-life shaping of subsequent cardiovascular function may come about, and suggest further studies that will be required in order to characterize the mechanisms responsible for these effects.     

Plant growth stimulation by inoculation with symbiotic and associative rhizosphere microorganisms

SelectedRhizobium bacteria, arbuscular mycorrhiza-forming (AM) fungi and associative bacteria have been shown to stimulate the growth of legumes, gramineae and cruciferae in field experiments on different soil types in temperate regions. A combination of microorganisms with different metabolic capacities (N₂-fixation, P-mobilization; production of phytohormones and antibiotics) can partly surpass the effect of single inoculations, or can produce a positive effect where single inoculations are ineffective. Growth stimulation by inoculation requires microorganisms with phytoeffective metabolic characteristics and the ability to survive in the rhizosphere during the growth period. Another prerequisite is an adequate supply of plant assimilates for the production of microbial phytoeffective metabolites. Type of inoculum, method of inoculation and agricultural measures can influence the effect of the inoculation. Research is necessary to extend our knowledge both of basic principles, and about using microorganisms in practice.     

Redox-driven proton translocation in methanogenic Archaea

Methanogenic archaea of the genus Methanosarcina are able to utilize H2 + CO2, methylated C1 compounds or acetate as energy and carbon source, thereby producing methane as the major end product. The methanogenic pathways lead to the formation of a mixed disulfide derived from coenzyme M and coenzyme B. This disulfide is of major importance for methanogens because it is the terminal electron acceptor of a branched respiratory chain. Molecular hydrogen, reduced coenzyme F420 or reduced ferredoxin are used as electron donors. Four enzymes are involved in the membrane-bound electron transport system of Methanosarcina species, all of which are involved in the generation of an electrochemical proton gradient that is used for ATP synthesis. This review focuses on the membrane-bound electron transport chains of Methanosarcina species with respect to the biochemical and genetic characteristics of the unusual energy transducing enzymes. Furthermore, the review addresses questions concerning the relationship between methanogenic proteins and components of respiratory chains found in bacteria and eukarya.     

Etude comparative des besoins minima en oxygène chez différentes espèces de Téléostéens

Summary The lowest levels of oxygen tension tolerated by 3 Teleost fishes were determined.Aequidens latifrons is able to survive at very low O₂ tensions which are lethal for the other species. This particularity can be correlated with ecological and physiological characters of this species.