Sensing by bacterial regulatory systems in host and non-host environments

Free-living organisms have the ability to gauge their surroundings and modify their gene expression patterns in ways that help them cope with new environments. Here we discuss the physiological significance of recent reports describing the ability of the Salmonella typhimurium PhoP/PhoQ two-component system to recognize and respond to host-derived antimicrobial peptides.     

Conflicting needs for a Salmonella hypervirulence gene in host and non-host environments

The Gram-negative pathogen Salmonella enterica harbours a periplasmic D-Ala-D-Ala dipeptidase (termed PcgL), which confers the ability to grow on D-Ala-D-Ala as sole carbon source. We now demonstrate that inactivation of the pcgL gene renders Salmonella hypervirulent. This phenotype results from the accumulation of peptidoglycan-derived D-Ala-D-Ala in the pcgL mutant and not from an intrinsically faster growth rate. Synthetic D-Ala-D-Ala (but not L-Ala-L-Ala or D-Ala) increased the number of wild-type Salmonella in the liver and spleen of mice within 24 h of injection, suggesting that D-Ala-D-Ala interferes with some aspect of innate immunity. However, the pcgL mutant was unable to grow on D-Ala-D-Ala as sole carbon source and was defective for survival in nutrient-poor conditions. We identified clinical isolates lacking D-Ala-D-Ala dipeptidase activity and unable to grow on D-Ala-D-Ala because of inactivation of the pcgL gene. Our data suggest that genes (such as pcgL) that, when mutated make pathogens more virulent, may be retained because their contribution to pathogen fitness in non-host environments outweighs potential advantages of the hypervirulent vari-ant in the infected host.     

The MgtC virulence factor of Salmonella enterica serovar Typhimurium activates Na(+),K(+)-ATPase

The mgtC gene of Salmonella enterica serovar Typhimurium encodes a membrane protein of unknown function that is important for full virulence in the mouse. Since mgtC is part of an operon with mgtB which encodes a Mg(2+)-transporting P-type ATPase, MgtC was hypothesized to function in ion transport, possibly in Mg(2+) transport. Consequently, MgtC was expressed in Xenopus laevis oocytes, and its effect on ion transport was evaluated using ion selective electrodes. Oocytes expressing MgtC did not exhibit altered currents or membrane potentials in response to changes in extracellular H(+), Mg(2+), or Ca(2+), thus ruling out a previously postulated function as a Mg(2+)/H(+) antiporter. However, addition of extracellular K(+) markedly hyperpolarized membrane potential instead of the expected depolarization. Addition of ouabain to block the oocyte Na(+),K(+)-ATPase completely prevented hyperpolarization and restored the normal K(+)-induced depolarization response. These results suggested that the Na(+),K(+)-ATPase was constitutively activated in the presence of MgtC resulting in a membrane potential largely dependent on Na(+),K(+)-ATPase. Consistent with the involvement of Na(+),K(+)-ATPase, oocytes expressing MgtC exhibited an increased rate of (86)Rb(+) uptake and had increased intracellular free [K(+)] and decreased free [Na(+)] and ATP. The free concentrations of Mg(2+) and Ca(2+) and cytosolic pH were unchanged, although the total intracellular Ca(2+) content was slightly elevated. These results suggest that the serovar Typhimurium MgtC protein may be involved in regulating membrane potential but does not directly transport Mg(2+) or another ion.     

The role of host population heterogeneity in the evolution of virulence

I examine here the effects of host heterogeneity in the growth of immune response on the evolution and co-evolution of virulence. The analysis is based on an extension of the 'nested model' by Gilchrist and Sasaki [Modeling host-parasite coevolution, J. Theor. Biol. 218 (2002), pp. 289-308]; the criteria for host and parasite evolution, in the paradigm of adaptive dynamics, for that model are derived in generality. Host heterogeneity is assumed to be fixed at birth according to a lognormal distribution or to the presence of two discrete types. In both cases, it is found that host heterogeneity determines a dramatic decrease in pathogen virulence, since pathogens will tune to the 'weakest' hosts. Finally we clarify how contrasting results present in the literature are due to different modelling assumptions.     

Evolution of pathogen virulence: the role of variation in host phenotype

Selection on pathogens tends to favour the evolution of growth and reproductive rates and a concomitant level of virulence (damage done to the host) that maximizes pathogen fitness. Yet, because hosts often pose varying selective environments to pathogens, one level of virulence may not be appropriate for all host types. Indeed, if a level of virulence confers high fitness to the pathogen in one host phenotype but low fitness in another host phenotype, alternative virulence strategies may be maintained in the pathogen population. Such strategies can occur either as polymorphism, where different strains of pathogen evolve specialized virulence strategies in different host phenotypes or as polyphenism, where pathogens facultatively express alternative virulence strategies depending on host phenotype. Polymorphism potentially leads to specialist pathogens capable of infecting a limited range of host phenotypes, whereas polyphenism potentially leads to generalist pathogens capable of infecting a wider range of hosts. Evaluating how variation among hosts affects virulence evolution can provide insight into pathogen diversity and is critical in determining how host pathogen interactions affect the phenotypic evolution of both hosts and pathogens.     

Dual RNA regulatory control of a Staphylococcus aureus virulence factor

In pathogens, the accurate programming of virulence gene expression is essential for infection. It is achieved by sophisticated arrays of regulatory proteins and ribonucleic acids (sRNAs), but in many cases their contributions and connections are not yet known. Based on genetic, biochemical and structural evidence, we report that the expression pattern of a Staphylococcus aureus host immune evasion protein is enabled by the collaborative actions of RNAIII and small pathogenicity island RNA D (SprD). Their combined expression profiles during bacterial growth permit early and transient synthesis of Sbi to avoid host immune responses. Together, these two sRNAs use antisense mechanisms to monitor Sbi expression at the translational level. Deletion analysis combined with structural analysis of RNAIII in complex with its novel messenger RNA (mRNA) target indicate that three distant RNAIII domains interact with distinct sites of the sbi mRNA and that two locations are deep in the sbi coding region. Through distinct domains, RNAIII lowers production of two proteins required for avoiding innate host immunity, staphylococcal protein A and Sbi. Toeprints and in vivo mutational analysis reveal a novel regulatory module within RNAIII essential for attenuation of Sbi translation. The sophisticated translational control of mRNA by two differentially expressed sRNAs ensures supervision of host immune escape by a major pathogen.     

The role of Streptococcus pneumoniae virulence factors in host respiratory colonization and disease

Streptococcus pneumoniae is a Gram-positive bacterial pathogen that colonizes the mucosal surfaces of the host nasopharynx and upper airway. Through a combination of virulence-factor activity and an ability to evade the early components of the host immune response, this organism can spread from the upper respiratory tract to the sterile regions of the lower respiratory tract, which leads to pneumonia. In this Review, we describe how S. pneumoniae uses its armamentarium of virulence factors to colonize the upper and lower respiratory tracts of the host and cause disease.     

Performance of leaf beetle larvae on sympatric host and non-host plants

Studies asking the ability of insects to utilize novel host plants often use novel hosts that are allopatric with the insect population under investigation. However, since the outcomes of species interactions are often site-specific, such studies cannot tell us whether a plant would actually be used by a given insect population if the plant grew sympatrically with it. We therefore performed a quantitative genetics experiment to analyse the performance of larvae of the leaf beetle Oreina elongata Suffrian (Coleoptera: Chrysomelidae, Chrysomelinae) on two host and three non-host plants, collected from a site where insects and plants co-occur in the Western Alps. When raised on the non-host Petasites albus (L.), larvae were able to survive equally well as on the two hosts, Adenostyles alliariae (Gouan) and Cirsium spinosissimum (L.), whereas they did not survive on the two other non-hosts, Peucedanum ostruthium (L.) and Rumex alpinus L. On P. albus, growth rate was slightly lower and development time slightly longer than on the two hosts. We found a genotype by environment interaction only for growth rate but not for development time and survival. However, the shape of the reaction norms of growth rates suggests that it is unlikely that selection could favour the inclusion of P. albus into the host range of the study population.     

Olfactory sensitivity of gomphocerine grasshoppers to the odours of host and non-host plants

Antennal responses to host and non-host odours were recorded, using the electroantennogram technique, from four gomphocerine grasshoppers with different feeding habits: Bootettix argentatus (monophagous on Larrea, a dicotyledonous plant), Ligurotettix coquilletti (oligophagous on dicotyledonous plants), Cibolacris parviceps (polyphagous) and Chorthippus curtipennis (graminivorous). The patterns of responses across the plant odours were similar for all four grasshopper species, but there was a relatively greater response to the odour of Larrea in B. argentatus and L. coquilletti which specialise on this plant. This suggests that there is considerable overall similarity in the make up of the olfactory receptor populations of these four grasshoppers species, but that some specificity for hostplant odour does exist at the antennal level.

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Résumé Les réponses antennaires ont été examinées par électroantennogramme aux odeurs de plantes hôtes et non hôtes d'orthoptères Gomphocerinae de comportements alimentaires différents: Bootettix argentatus, monophage sur une dicotylédone, Larrea; Ligurotettix coquilletti, oligophage de dicotylédones; Cibolacris parviceps, polyphage; Chorthippus curtipennis, graminivore.Les types de réponse des quatre espèces étaient très voisins, mais les réponses aux odeurs de Larrea de B. argentatus et L. coquilletti, spécialistes de cette plante, étaient relativement plus fortes. Ces résultats suggèrent une similarité globale considérable dans la composition des populations de récepteurs olfactifs de ces quatre espèces d'orthoptères mais aussi une certaine spécificité pour les odeurs de la plante hôte au niveau antennaire.

     

Effect of crop rotations involving host and non-host plants on vesicular-arbuscular mycorrhizal infection of host plants

Summary The effects of crop rotations involving two host (lettuce and lavender) and two non-host (cabbage and radish) plants on the development of mycorrhizal infection in host plants were studied in unsterile soil and in sterilized soil with or without rock phosphate and inoculated withGlomus mosseae. As in previous experiments, pre-cropping with non-host plants did not decrease VA infection in the host plants. On the other hand, pre-cropping with a host plant increased VA infection in the same or another host plant grown afterwards. These effects were noted irrespectively of rock phosphate additions and of soil sterilization.     

Local host competition in the evolution of virulence

The evolution of parasite life histories should usually have correlated effects on host survivorship and/or reproductive success. For example, parasites that reproduce more rapidly might be expected to cause greater reductions in host fitness. Important theoretical advances have recently been made on virulence evolution, but the results are not always consistent. Here I compare two models [ Q. Rev. Biol. 71 (1996) 37 ; Q. Rev. Biol. 75 (2000) 261 ] on the evolution of virulence that get qualitatively different results with respect to the effects of coinfection. I also construct a third model that attempts to connect these two formulations. The results suggest that parasite growth rates should increase as local host competition increases, unless relatedness is at equilibrium. In addition, the qualitative effect of adding coinfections on parasite growth rates depends critically on how the number of coinfections affects transmission success.     

Dual role of tumor necrosis factor alpha in brain injury

Brain injury (ischemia, trauma) is among the leading cause of mortality and disability in the western world. It induces increased production of tumor necrosis factor (TNF alpha) by brain resident cells. There is conflicting evidence on the role of this response in the injured brain, showing its potential effect in both processes of repair and of damage. This review presents data from clinical and experimental studies on the stimulation of TNF alpha production in brain injury and on the deleterious consequence of this acute response. Its inhibition by pharmacologic agents, neutralizing antibodies or soluble receptors has protective effects. In contrast, there are reports (from in-vitro studies or knock-out mice) on the beneficial effects of TNF alpha. To reconcile these apparently conflicting reports, the exact timing and extent of TNF alpha activation must be taken into account, as well as the presence of other mediators such as reactive oxygen species. It is suggested that the appropriate context of mediators, at any given time after brain injury may well determine whether the effect of TNF alpha is protective or toxic.