The evolutionary costs of immunological maintenance and deployment

<p>Abstract</p> <p>Background</p> <p>The evolution of disease resistance and immune function may be limited if increased immunocompetence comes at the expense of other fitness-determining traits. Both the maintenance of an immune system and the deployment of an immune response can be costly, and the observed costs may be evaluated as either physiological or evolutionary in origin. Evolutionary costs of immunological maintenance are revealed as negative genetic correlations between immunocompetence and fitness in the absence of infection. Costs of deployment are most often studied as physiological costs associated with immune system induction, however, evolutionary costs of deployment may also be present if genotypes vary in the extent of the physiological cost experienced.</p> <p>Results</p> <p>In this study we analyzed evolutionary and physiological costs of immunity in two environments representing food-limited and food-unlimited conditions. Patterns of genetic variation were estimated in females from 40 'hemiclone families' isolated from a population of <it>D. melanogaster</it>. Phenotypes evaluated included fecundity, weight measures at different time periods and resistance to <it>Providencia rettgeri</it>, a naturally occurring Gram-negative pathogen of <it>D. melanogaster</it>. In the food-limited environment we found a negative genetic correlation between fecundity in the absence of infection and resistance, indicative of an evolutionary cost of maintenance. No such correlation was observed in the food-unlimited environment, and the slopes of these correlations significantly differed, demonstrating a genotype-by-environment interaction for the cost of maintenance. Physiological costs of deployment were also observed, but costs were primarily due to wounding. Deployment costs were slightly exaggerated in the food-limited environment. Evolutionary costs of immunological deployment on fecundity were not observed, and there was only marginally significant genetic variation in the cost expressed by changes in dry weight.</p> <p>Conclusion</p> <p>Our results suggest that the costs of immunity may be an important factor limiting the evolution of resistance in food-limited environments. However, the significant genotype-by-environment interaction for maintenance costs, combined with the observation that deployment costs were partially mitigated in the food-unlimited environment, emphasizes the importance of considering environmental variation when estimating patterns of genetic variance and covariance, and the dubious nature of predicting evolutionary responses to selection from quantitative genetic estimates carried out in a single environment.</p

Inhibition of Biofilm Formation, Quorum Sensing and Infection in Pseudomonas aeruginosa by Natural Products-Inspired Organosulfur Compounds

Using a microplate-based screening assay, the effects on Pseudomonas aeruginosa PAO1 biofilm formation of several S-substituted cysteine sulfoxides and their corresponding disulfide derivatives were evaluated. From our library of compounds, S-phenyl-L-cysteine sulfoxide and its breakdown product, diphenyl disulfide, significantly reduced the amount of biofilm formation by P. aeruginosa at levels equivalent to the active concentration of 4-nitropyridine-N-oxide (NPO) (1 mM). Unlike NPO, which is an established inhibitor of bacterial biofilms, our active compounds did not reduce planktonic cell growth and only affected biofilm formation. When used in a Drosophila-based infection model, both S-phenyl-L-cysteine sulfoxide and diphenyl disulfide significantly reduced the P. aeruginosa recovered 18 h post infection (relative to the control), and were non-lethal to the fly hosts. The possibility that the observed biofilm inhibitory effects were related to quorum sensing inhibition (QSI) was investigated using Escherichia coli-based reporters expressing P. aeruginosa lasR or rhIR response proteins, as well as an endogenous P. aeruginosa reporter from the lasI/lasR QS system. Inhibition of quorum sensing by S-phenyl-L-cysteine sulfoxide was observed in all of the reporter systems tested, whereas diphenyl disulfide did not exhibit QSI in either of the E. coli reporters, and showed very limited inhibition in the P. aeruginosa reporter. Since both compounds inhibit biofilm formation but do not show similar QSI activity, it is concluded that they may be functioning by different pathways. The hypothesis that biofilm inhibition by the two active compounds discovered in this work occurs through QSI is discussed

The evolution of resistance to Simian Immunodeficiency Virus (SIV): A review

Abstract Examining how pathogens cross species boundaries, spread within species, and persist within their hosts is an essential part of understanding the factors that underpin the evolution of virulence and host resistance. Here, we review current knowledge about the genetic diversity, molecular epidemiology, prevalence, and pathogenicity of simian immunodeficiency viruses (SIVs). SIVs have crossed species boundaries from simian hosts to humans on at least 12 separate occasions, one of which led to the global HIV-AIDS crisis. Though SIVs infect a wide range of primates, scientists have only recently begun to describe the natural history of SIV infection in their natural hosts. Several new studies reveal how both viral and host factors are responsible for the transmission to, and adaptation in, new hosts. These studies also suggest that the spread of the virus may be affected by host-specific traits, including social structure, mating system and demographic history. These studies challenge the traditional view that SIV is relatively benign in its natural host, and instead suggest that a highly dynamic relationship exists between SIV and its simian hosts

Why Are Nigeria-Cameroon Chimpanzees (Pan troglodytes ellioti) Free of SIVcpz Infection?

Simian immunodeficiency virus (SIV) naturally infects two subspecies of chimpanzee: Pan troglodytes troglodytes from Central Africa (SIVcpzPtt) and P. t. schweinfurtii from East Africa (SIVcpzPts), but is absent in P. t. verus from West Africa and appears to be absent in P. t. ellioti inhabiting Nigeria and western Cameroon. One explanation for this pattern is that P. t. troglodytes and P. t schweinfurthii may have acquired SIVcpz after their divergence from P. t. verus and P. t. ellioti. However, all of the subspecies, except P. t. verus, still occasionally exchange migrants making the absence of SIVcpz in P. t. ellioti puzzling. Sampling of P. t. ellioti has been minimal to date, particularly along the banks of the Sanaga River, where its range abuts that of P. t. troglodytes. This study had three objectives. First, we extended the sampling of SIVcpz across the range of chimpanzees north of the Sanaga River to address whether under-sampling might account for the absence of evidence for SIVcpz infection in P. t. ellioti. Second, we investigated how environmental variation is associated with the spread and prevalence of SIVcpz in the two chimpanzee subspecies inhabiting Cameroon since environmental variation has been shown to contribute to their divergence from one another. Finally, we compared the prevalence and distribution of SIVcpz with that of Simian Foamy Virus (SFV) to examine the role of ecology and behavior in shaping the distribution of diseases in wild host populations. The dataset includes previously published results on SIVcpz infection and SFVcpz as well as newly collected data, and represents over 1000 chimpanzee fecal samples from 41 locations across Cameroon. Results revealed that none of the 181 P. t. ellioti fecal samples collected across the range of P. t. ellioti tested positive for SIVcpz. In addition, species distribution models suggest that environmental variation contributes to differences in the distribution and prevalence of SIVcpz and SFVcpz. The ecological niches of these two viruses are largely non-overlapping, although stronger statistical support for this conclusion will require more sampling. Overall this study demonstrates that SIVcpz infection is absent or very rare in P. t. ellioti, despite multiple opportunities for transmission. The reasons for its absence remain unclear, but might be explained by one or more factors, including environmental variation, viral competition, and/or local adaptation-all of which should be explored in greater detail through continued surveillance of this region

Effects of compounds 7 and 12 on <i>D. melanogaster</i> infected with <i>P. aeruginosa</i> PAO1.

<p>Treatment groups not connected by the same symbol are significantly different from each other, as determined by ANOVA (p<0.01) and Tukey’s test (p<0.05).</p

Cell viability within microplate-established biofilms as determined by the MTT assay.

<p>Biofilms were grown in the presence of 1 mM of compounds <b>7</b>, <b>12</b> and NPO. ANOVA (p<0.0001) was performed, followed by Tukey’s test, with asterisks (*) indicating significant (p<0.01) reduction in viability as compared to the no inhibitor control (n = 5).</p