ABSTRACT Bacteria in their natural environments frequently exist as mixed surface-associated communities, protected by extracellular material, termed biofilms. Biofilms formed by the human pathogen Campylobacter jejuni may arise in the gastrointestinal tract of animals but also in water pipes and other industrial situations, leading to their possible transmission into the human food chain either directly or via farm animals. Bacteriophages are natural predators of bacteria that usually kill their prey by cell lysis and have potential application for the biocontrol and dispersal of target bacteria in biofilms. The effects of virulent Campylobacter specific-bacteriophages CP8 and CP30 on C. jejuni biofilms formed on glass by strains NCTC 11168 and PT14 at 37°C under microaerobic conditions were investigated. Independent bacteriophage treatments (n ≥ 3) led to 1 to 3 log10 CFU/cm2 reductions in the viable count 24 h postinfection compared with control levels. In contrast, bacteriophages applied under these conditions effected a reduction of less than 1 log10 CFU/ml in planktonic cells. Resistance to bacteriophage in bacteria surviving bacteriophage treatment of C. jejuni NCTC 11168 biofilms was 84% and 90% for CP8 and CP30, respectively, whereas bacteriophage resistance was not found in similarly recovered C. jejuni PT14 cells. Dispersal of the biofilm matrix by bacteriophage was demonstrated by crystal violet staining and transmission electron microscopy. Bacteriophage may play an important role in the control of attachment and biofilm formation by Campylobacter in situations where biofilms occur in nature, and they have the potential for application in industrial situations leading to improvements in food safety.

Many agricultural pest species occur in seasonal metapopulations with a period of asexual reproduction. We use evolutionary theory to predict timing of dispersal for such species, and identify four sequential phases: no dispersal, dispersal from initially occupied patches, dispersal from later colonized patches, and no dispersal. The third type of phase occurs only when reproductive rates are relatively high; we speculate that this could explain why among aphids there can be either one or two waves of dispersal during a season, depending on the species. Our model also explains other features of aphid biology, including a summer crash in colony size, and a decline in the number of colonies towards the end of each reproductive season. The presence of an additional surge of dispersal becomes more likely as season length increases, and does not require further evolution. This could have profound implications for pest management during future climatic warming.

The dominant metric for setting public health priorities, the disability-adjusted life year (DALY), is unsuited to parasitic infections. In particular, the current DALY framework fails to acknowledge the non-linear pathologies of infection, the community level dynamics of epidemiology and the co-morbidities of polyparasitism. Parasitologists must urgently provide a better way of accounting for the true costs of parasitic disease.

The monthly incidence of listeriosis infections in England and Wales had 2 sudden increases during April 2001 (41%) and March 2003 (48%). Although no causative association is demonstrated, these increases correspond to key dates relating to the onset and aftermath of the 2001 foot and mouth disease outbreak in the United Kingdom.

Phage therapy is the use of bacteriophages as antimicrobial agents for the control of pathogenic and other problem bacteria. It has previously been argued that successful application of phage therapy requires a good understanding of the non-linear kinetics of phage-bacteria interactions. Here we combine experimental and modelling approaches to make a detailed examination of such kinetics for the important food-borne pathogen Campylobacter jejuni and a suitable virulent phage in an in vitro system. Phage-insensitive populations of C. jejuni arise readily, and as far as we are aware this is the first phage therapy study to test, against in vitro data, models for phage-bacteria interactions incorporating phage-insensitive or resistant bacteria. We find that even an apparently simplistic model fits the data surprisingly well, and we confirm that the so-called inundation and proliferation thresholds are likely to be of considerable practical importance to phage therapy. We fit the model to time series data in order to estimate thresholds and rate constants directly. A comparison of the fit for each culture reveals density-dependent features of phage infectivity that are worthy of further investigation. Our results illustrate how insight from empirical studies can be greatly enhanced by the use of kinetic models: such combined studies of in vitro systems are likely to be an essential precursor to building a meaningful picture of the kinetic properties of in vivo phage therapy.

Background Local activation of Rho GTPases is important for many functions including cell polarity, morphology, movement, and growth. Although a number of molecules affecting Rho-of-Plants small GTPase (ROP) signalling are known, it remains unclear how ROP activity becomes spatially organised. Arabidopsis root hair cells produce patches of ROP at consistent and predictable subcellular locations, where root hair growth subsequently occurs. Methodology/Principal Findings We present a mathematical model to show how interaction of the plant hormone auxin with ROPs could spontaneously lead to localised patches of active ROP via a Turing or Turing-like mechanism. Our results suggest that correct positioning of the ROP patch depends on the cell length, low diffusion of active ROP, a gradient in auxin concentration, and ROP levels. Our theory provides a unique explanation linking the molecular biology to the root hair phenotypes of multiple mutants and transgenic lines, including OX-ROP, CA-rop, aux1, axr3, tip1, eto1, etr1, and the triple mutant aux1 ein2 gnomeb. Conclusions/Significance We show how interactions between Rho GTPases (in this case ROPs) and regulatory molecules (in this case auxin) could produce characteristic subcellular patterning that subsequently affects cell shape. This has important implications for research on the morphogenesis of plants and other eukaryotes. Our results also illustrate how gradient-regulated Turing systems provide a particularly robust and flexible mechanism for pattern formation.

We use kinetic models to investigate how to design antimicrobial phage therapies to minimize emergence of resistant bacteria. We do this by modifying the "mutant selection window" hypothesis in a way that accounts for the ongoing self-replication of the phage. We show that components of combination phage therapies need to be appropriately matched if treatment is to avoid the emergence of resistant bacteria. Matching of components is more easily achieved when phage dosages are high enough that ongoing phage replication is not needed for the clearance of the bacteria. Theoretical predictions such as ours need to be tested experimentally if applications of phage therapy are to avoid the problems of widespread resistance that have beset chemical antibiotics.

Use of bacteriophage to control bacterial infections, including antibiotic-resistant infections, shows increasing therapeutic promise. Effective bacteriophage therapy requires awareness of various novel kinetic phenomena not known in conventional drug treatments. Kinetic theory predicts that timing of treatment could be critical, with the strange possibility that inoculations given too early could be less effective or fail completely. Another paradoxical result is that adjuvant use of an antibiotic can sometimes diminish the efficacy of phage therapy. For a simple kinetic model, mathematical formulae predict the values of critical density thresholds and critical time points, given as functions of independently measurable biological parameters. Understanding such formulae is important for interpreting data and guiding experimental design. Tailoring pharmacokinetic models for specific systems needs to become standard practice in future studies.

Both experiments (5) and theory (3, 4) have suggested that for a population of phage to increase in numbers requires the host cell population to surpass a critical density termed the " replication threshold " or the " proliferation threshold. " However , recently in the Journal of Virology, Kasman et al. (1) argued that no such threshold exists. Why this discrepancy? For a population of phage to increase in numbers, not only must phage from the initial dose replicate but also progeny phage must survive long enough to sustain further replication. This in turn depends on the density of remaining uninfected cells and on the rate of loss of free phage. The proliferation threshold is that cell density above which the probability of a progeny phage replicating is greater than the probability of that phage being lost (4). From this we identify three ways to reconcile the apparent inconsistencies between Kasman et al. (1) and Wiggins and Alexander (5). First, the rate of phage loss in vitro is many times lower than in natural systems such as in sewage or in vivo. Consequently, the proliferation threshold is expected a priori to be much lower in in vitro experiments such as those of Kasman et al. (1) than in any in vivo system, maybe even too small to measure. Wiggins and Alexander (5) assessed different rates of phage loss, but they were not reported by Kasman et al. If relevant parameter estimates were available, then the proliferation threshold could be predicted using a formula derived from kinetic theory (4). Second, where Kasman et al. use an actual multiplicity of infection of 10, the bacterial infection rate is so high that there are effectively no uninfected cells left for progeny phage to infect: inundation by the initial phage renders any subsequent phage replication or density threshold irrelevant. Kinetic theory predicts that the proliferation threshold is manifested only if the initial phage dose is much smaller than the actual multiplicity of infection of 10 (technically, the phage dose must be less than the " inundation threshold " but more than the " failure threshold " [4]). Third, in natural systems of interest the host cell density typically increases with time. Thus, if the initial cell density is low, it takes a certain time before the proliferation threshold is crossed and thereby made observable. Wiggins and Alexander made this transparent using explicit time …

In a recent TREE News & Comment, Bridle and Jiggins 1 Bridle J.R. Jiggins C.D. Adaptive dynamics: is speciation too easy?. Trends Ecol. Evol. 2000; 15: 225-226 Abstract Full Text Full Text PDF Scopus (18) Google Scholar discuss growing empirical support for sympatric speciation, and for putative mechanisms that might underlie its occurrence. They dwell primarily on disruptive natural selection, touching only fleetingly on how disruptive sexual selection could drive sympatric speciation via assortative mating, leading to divergent Fisherian runaway processes 2 Fisher R.A. The Genetical Theory of Natural Selection. Clarendon Press, 1930 Google Scholar . Two models have formally addressed disruptive sexual selection: our own in 1997 ( 3 Payne R.J.H. Krakauer D.C. Sexual selection, space and speciation. Evolution. 1997; 51: 1-9 Crossref Google Scholar ) and a more recent model by Higashi et al.4 Higashi M. et al. Sympatric speciation by sexual selection. Nature. 1999; 402: 523-526 Crossref PubMed Scopus (277) Google Scholar These models rely on different behavioural assumptions, but both are underpinned by a bifurcating Fisherian process. Thus, a comparison of the models might offer insight into factors essential to sympatric speciation by disruptive sexual selection. Reply from J.R. Bridle, C.D. Jiggins and T. TregenzaBridle et al.Trends in Ecology & EvolutionOctober 01, 2000In Brief Full-Text PDF