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In the Americas, transgenic crops producing insecticidal proteins from Bacillus thuringiensis Berliner (Bt, Bacillales: Bacillaceae) have been used widely to manage fall armyworm (FAW, Spodoptera frugiperda [J.E. Smith]). As resistance to Cry1 single-gene Bt maize (Zea mays L.) rapidly evolved in some FAW populations, pyramided Bt maize hybrids producing Cry1, Cry2, or Vip3Aa proteins were introduced in the 2010s. We examined field-evolved resistance to single- and dual-protein Bt maize hybrids in 2 locations in southeastern Brazil, where plant damage by FAW larvae far exceeded the economic threshold in 2017. We collected late-instar larvae in Cry1A.105 + Cry2Ab and Cry1F maize fields and established 2 FAW populations in the laboratory. The F1 offspring reared on the foliage of Bt and non-Bt maize plants (Cry1A.105 + Cry2Ab and Cry1F) showed neonate-to-adult survival rates as high as 70% for both populations. There was no significant difference in the life-table parameters of armyworms reared on non-Bt and Bt maize foliage, indicating complete resistance to Cry1A.105 + Cry2Ab maize. Larval survival rates of reciprocal crosses of a susceptible laboratory strain and the field-collected populations indicated nonrecessive resistance to Cry1F and a recessive resistance to Cry1A.105 + Cry2Ab maize. When relaxing the selection pressure, the armyworm fitness varied on Cry1A.105 + Cry2Ab and non-Bt maize; the resistance was somewhat stable across 12 generations, without strong fitness costs, although one of the lines died confounded by a depleted-quality, artificial rearing diet. To our knowledge, this is the first report documenting the practical resistance of FAW to a pyramided Bt crop. We discuss the implications for resistance management.

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Since the Origin of Species, it has been known that evolution depends on what Darwin called the "strong principle of inheritance." Highly accurate replication of cellular phenotype is a universal phenomenon in all of life since LUCA and is often taken for granted as a constant in evolutionary theory. It is not known how self-replication arose during the origin of life. In this report I use the simple mathematics of evolutionary theory to investigate the dynamics of self-replication accuracy and allelic selection. Results indicate that the degree of self-replication accuracy must be greater than a threshold related to the selection coefficients of the alleles in a population in order for evolution to occur. Accurate replication of cellular phenotype and of the molecules involved in genotype/phenotype linkage is necessary for the origin of evolution and may be considered the fundamental principle of life.

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Multidrug efflux pumps are the frontline defense mechanisms of Gram-negative bacteria, yet little is known of their relative fitness trade-offs under gut conditions such as low pH and the presence of antimicrobial food molecules. Low pH contributes to the proton-motive force (PMF) that drives most efflux pumps. We show how the PMF-dependent pumps AcrAB-TolC, MdtEF-TolC, and EmrAB-TolC undergo selection at low pH and in the presence of membrane-permeant phytochemicals. Competition assays were performed by flow cytometry of co-cultured Escherichia coli K-12 strains possessing or lacking a given pump complex. All three pumps showed negative selection under conditions that deplete PMF (pH 5.5 with carbonyl cyanide 3-chlorophenylhydrazone or at pH 8.0). At pH 5.5, selection against AcrAB-TolC was increased by aromatic acids, alcohols, and related phytochemicals such as methyl salicylate. The degree of fitness cost for AcrA was correlated with the phytochemical's lipophilicity (logP). Methyl salicylate and salicylamide selected strongly against AcrA, without genetic induction of drug resistance regulons. MdtEF-TolC and EmrAB-TolC each had a fitness cost at pH 5.5, but salicylate or benzoate made the fitness contribution positive. Pump fitness effects were not explained by gene expression (measured by digital PCR). Between pH 5.5 and 8.0, acrA and emrA were upregulated in the log phase, whereas mdtE expression was upregulated in the transition-to-stationary phase and at pH 5.5 in the log phase. Methyl salicylate did not affect pump gene expression. Our results suggest that lipophilic non-acidic molecules select against a major efflux pump without inducing antibiotic resistance regulons.IMPORTANCEFor drugs that are administered orally, we need to understand how ingested phytochemicals modulate drug resistance in our gut microbiome. Bacteria maintain low-level resistance by proton-motive force (PMF)-driven pumps that efflux many different antibiotics and cell waste products. These pumps play a key role in bacterial defense by conferring resistance to antimicrobial agents at first exposure while providing time for a pathogen to evolve resistance to higher levels of the antibiotic exposed. Nevertheless, efflux pumps confer energetic costs due to gene expression and pump energy expense. The bacterial PMF includes the transmembrane pH difference (ΔpH), which may be depleted by permeant acids and membrane disruptors. Understanding the fitness costs of efflux pumps may enable us to develop resistance breakers, that is, molecules that work together with antibiotics to potentiate their effect. Non-acidic aromatic molecules have the advantage that they avoid the Mar-dependent induction of regulons conferring other forms of drug resistance. We show that different pumps have distinct selection criteria, and we identified non-acidic aromatic molecules as promising candidates for drug resistance breakers.

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Nanoparticle pollution has been shown to affect various organisms. However, the effects of nanoparticles on species interactions, and the role of species traits, such as body size, in modulating these effects, are not well-understood. We addressed this issue using competing freshwater phytoplankton species exposed to copper oxide nanoparticles. Increasing nanoparticle concentration resulted in decreased phytoplankton species growth rates and community productivity (both abundance and biomass). Importantly, we consistently found that nanoparticles had greater negative effects on species with smaller cell sizes, such that nanoparticle pollution weakened the competitive dominance of smaller species and promoted species diversity. Moreover, nanoparticles reduced the growth rate differences and competitive ability differences of competing species, while having little effect on species niche differences. Consequently, nanoparticle pollution reduced the selection effect on phytoplankton community abundance, but increased the selection effect on community biomass. Our results suggest cell size as a key functional trait to consider when predicting phytoplankton community structure and ecosystem functioning in the face of increasing nanopollution.

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Despite increasing knowledge of the fitness costs of viability and fecundity involved in the herbicide-resistant weeds, relatively little is known about the linkage between herbicide resistance costs and phytochemical cues in weed species and biotypes. This study demonstrated relative fitness and phytochemical responses in six herbicide-resistant weeds and their susceptible counterparts. There were significant differences in the parameters of viability (growth and photosynthesis), fecundity fitness (flowering and seed biomass) and a ubiquitous phytochemical (-)-loliolide levels between herbicide-resistant weeds and their susceptible counterparts. Fitness costs occurred in herbicide-resistant Digitaria sanguinalis and Leptochloa chinensis but they were not observed in herbicide-resistant Alopecurus japonicas, Eleusine indica, Ammannia arenaria, and Echinochloa crus-galli. Correlation analysis indicated that the morphological characteristics of resistant and susceptible weeds were negatively correlated with (-)-loliolide concentration, but positively correlated with lipid peroxidation malondialdehyde and total phenol contents. Principal component analysis showed that the lower the (-)-loliolide concentration, the stronger the adaptability in E. crus-galli and E. indica. Therefore, not all herbicide-resistant weeds have fitness costs, but the findings showed several examples of resistance leading to improved fitness even in the absence of herbicides. In particular, (-)-loliolide may act as a phytochemical cue to explain the fitness cost of herbicide-resistant weeds by regulating vitality and fecundity.

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Antimicrobial resistance (AMR) in bacteria implies a tradeoff between the benefit of resistance under antimicrobial selection pressure and the incurred fitness cost in the absence of antimicrobials. The fitness cost of a resistance determinant is expected to depend on its genetic support, such as a chromosomal mutation or a plasmid acquisition, and on its impact on cell metabolism, such as an alteration in an essential metabolic pathway or the production of a new enzyme. To provide a global picture of the factors that influence AMR fitness cost, we conducted a systematic review and meta-analysis focused on a single species, Escherichia coli. By combining results from 46 high-quality studies in a multilevel meta-analysis framework, we find that the fitness cost of AMR is smaller when provided by horizontally transferable genes such as those encoding beta-lactamases, compared to mutations in core genes such as those involved in fluoroquinolone and rifampicin resistance. We observe that the accumulation of acquired AMR genes imposes a much smaller burden on the host cell than the accumulation of AMR mutations, and we provide quantitative estimates of the additional cost of a new gene or mutation. These findings highlight that gene acquisition is more efficient than the accumulation of mutations to evolve multidrug resistance, which can contribute to the observed dominance of horizontally transferred genes in the current AMR epidemic.

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This study was designed to evaluate the synergistic effect of phage and antibiotic on the induction of collateral sensitivity in Salmonella Typhimurium. The synergistic effects of Salmonella phage PBST32 combined with ciprofloxacin (CIP) against S. Typhimurium KCCM 40253 (STKCCM) were evaluated using a fractional inhibitory concentration (FIC) assay. The CIP susceptibility of STKCCM was increased when combined with PBST32, showing 16-fold decrease at 7 log PFU/mL. The combination of 1/2 × MIC of CIP and PBST32 (CIP[1/2]+PBST32) effectively inhibited the growth of STKCCM up to below the detection limit (1.3 log CFU/mL) after 12 h of incubation at 37 °C. The significant reduction in bacterial swimming motility was observed for PBST32 and CIP[1/4]+PBST32. The CIP[1/4]+PBST32 increased the fitness cost (relative fitness = 0.57) and decreased the cross-resistance to different classes of antibiotics. STKCCM treated with PBST32 alone treatment exhibited the highest coefficient of variation (90%), followed by CIP[1/4]+PBST32 (75%). These results suggest that the combination of PBST32 and CIP can be used to control bacterial pathogens.

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The long-term evolution experiment (LTEE) with Escherichia coli began in 1988 and it continues to this day, with its 12 populations having recently reached 75,000 generations of evolution in a simple, well-controlled environment. The LTEE was designed to explore open-ended questions about the dynamics and repeatability of phenotypic and genetic evolution. Here I discuss various aspects of the LTEE's experimental design that have enabled its stability and success, including the choices of the culture regime, growth medium, ancestral strain, and statistical replication. I also discuss some of the challenges associated with a long-running project, such as handling procedural errors (e.g., cross-contamination) and managing the expanding collection of frozen samples. The simplicity of the experimental design and procedures have supported the long-term stability of the LTEE. That stability-along with the inherent creativity of the evolutionary process and the emergence of new genomic technologies-provides a platform that has allowed talented students and collaborators to pose questions, collect data, and make discoveries that go far beyond anything I could have imagined at the start of the LTEE.

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Competition is among the most important factors regulating plant population and community dynamics, but we know little about how different vital rates respond to competition and jointly determine population growth and species coexistence. We conducted a field experiment and parameterised integral projection models to model the population growth of 14 herbaceous plant species in the absence and presence of neighbours across an elevation gradient (284 interspecific pairs). We found that suppressed individual growth and seedling establishment contributed the most to competition-induced declines in population growth, although vital rate contributions varied greatly between species and with elevation. In contrast, size-specific survival and flowering probability and seed production were frequently enhanced under competition. These compensatory vital rate responses were nearly ubiquitous (occurred in 92% of species pairs) and significantly reduced niche overlap and stabilised coexistence. Our study highlights the importance of demographic processes for regulating population and community dynamics, which has often been neglected by classic coexistence theories.

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The environmental context of the nitrogen-fixing mutualism between leguminous plants and rhizobial bacteria varies over space and time. Variation in resource availability, population density, and composition likely affect the ecology and evolution of rhizobia and their symbiotic interactions with hosts. We examined how host genotype, nitrogen addition, rhizobial density, and community complexity affected selection on 68 rhizobial strains in the Sinorhizobium meliloti-Medicago truncatula mutualism. As expected, host genotype had a substantial effect on the size, number, and strain composition of root nodules (the symbiotic organ). The understudied environmental variable of rhizobial density had a stronger effect on nodule strain frequency than the addition of low nitrogen levels. Higher inoculum density resulted in a nodule community that was less diverse and more beneficial but only in the context of the more selective host genotype. Higher density resulted in more diverse and less beneficial nodule communities with the less selective host. Density effects on strain composition deserve additional scrutiny as they can create feedback between ecological and evolutionary processes. Finally, we found that relative strain rankings were stable across increasing community complexity (2, 3, 8, or 68 strains). This unexpected result suggests that higher-order interactions between strains are rare in the context of nodule formation and development. Our work highlights the importance of examining mechanisms of density-dependent strain fitness and developing theoretical predictions that incorporate density dependence. Furthermore, our results have translational relevance for overcoming establishment barriers in bioinoculants and motivating breeding programs that maintain beneficial plant-microbe interactions across diverse agroecological contexts. IMPORTANCE Legume crops establish beneficial associations with rhizobial bacteria that perform biological nitrogen fixation, providing nitrogen to plants without the economic and greenhouse gas emission costs of chemical nitrogen inputs. Here, we examine the influence of three environmental factors that vary in agricultural fields on strain relative fitness in nodules. In addition to manipulating nitrogen, we also use two biotic variables that have rarely been examined: the rhizobial community's density and complexity. Taken together, our results suggest that (i) breeding legume varieties that select beneficial strains despite environmental variation is possible, (ii) changes in rhizobial population densities that occur routinely in agricultural fields could drive evolutionary changes in rhizobial populations, and (iii) the lack of higher-order interactions between strains will allow the high-throughput assessments of rhizobia winners and losers during plant interactions.

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Exogenous genes of transgenic crops are usually transferred to their wild-type relatives through pollen-mediated gene flow, which may change the ecological fitness and ability to invade wild populations, resulting in the weeding of wild plants and other unpredictable environmental impacts. In this study, the F1 generation of herbicide-resistant soybeans and wild soybeans was obtained by artificial pollination, F2 generation seeds were obtained by self-crossing, and the fitness of the parents and their F1 and F2 generations were tested. The foreign protein EPSPS was expressed normally in the hybrid between transgenic and wild soybeans; however, the protein expression was significantly lower than that in transgenic soybeans. The fitness of the F1 hybrid between transgenic and wild soybeans was significantly lower than that of its parent. Compared with those of the wild soybeans, the F2 generation soybeans improved in some fitness indices, while the emergence rate, pollen germination rate, and number of full seeds per pod, pods per plant, and full seeds per plant did not significantly differ. The aboveground biomass and 100-seed weight of the F2 generation were higher than those of wild soybeans. Fitness among the F2-negative plants, homozygous, and heterozygous positive plants did not significantly vary. Improved fitness and presence of foreign genes in the F2 soybean were not significantly correlated. As the F2 generation of transgenic and wild soybeans had no fitness cost and the flowering stage were overlapped, the foreign gene might still spread in the wild soybean population.

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Response of microbial community to nutrient availability in anaerobic digestion (AD) remains elusive. Prokaryotic communities in AD batch cultures with 0, 1, 3, 5, 7, 11, 15, 20, and 25 g/L peptone were monitored using massive parallel sequencing and quantitative PCR over a 34-day experimental period. Methane production displayed a hump-shaped response to the nutrient gradient (peaking at 15 g/L peptone). Moreover, total and acetoclastic methanogens showed hump-shaped responses (both peaking at 11 g/L peptone). However, prokaryotic population increased with nutrient concentration (linear regression, R2 = 0.86) while diversity decreased (R2 = 0.94), and ordination analysis showed a gradual succession of community structure along the first axis. Network analysis revealed that extent of interspecific interactions (e.g., edge number and clustering coefficient) exhibited a hump-shaped response. The combined results indicate that abundant species became more dominated with increasing nutrient, which can result in a gain or loss of interspecific interaction within the community. Network module analysis showed that one module dominated the network at each nutrient level (comprising 41%-65% of the nodes), indicating that AD community formed a core microbial guild. The most abundant phylotypes, Macellibacteroides and Butyricicoccaceae, were consistently negative with acetoclastic methanogens in the dominant modules. Their predominance at ≥15 g/L peptone can explain the hump-shaped responses of methanogenesis and methanogens. Collectively, methanogenesis and microbial network exhibited hump-shaped responses, although microbial community exhibited monotonic responses. Therefore, nutrient availability can determine the methanogenesis through regulating the relative fitness of methanogens within the community.

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Antibiotic resistance is a growing concern that has prompted a renewed focus on drug discovery, stewardship, and evolutionary studies of the patterns and processes that underlie this phenomenon. A resistant strain's competitive fitness relative to its sensitive counterparts in the absence of drug can impact its spread and persistence in both clinical and community settings. In a prior study, we examined the fitness of tetracycline-resistant clones that evolved from five different Escherichia coli genotypes, which had diverged during a long-term evolution experiment. In this study, we build on that work to examine whether ampicillin-resistant mutants are also less fit in the absence of the drug than their sensitive parents, and whether the cost of resistance is constant or variable among independently derived lines. Like the tetracycline-resistant lines, the ampicillin-resistant mutants were often less fit than their sensitive parents, with significant variation in the fitness costs among the mutants. This variation was not associated with the level of resistance conferred by the mutations, nor did it vary across the different parental backgrounds. In our earlier study, some of the variation in fitness costs associated with tetracycline resistance was explained by the effects of different mutations affecting the same cellular pathway and even the same gene. In contrast, the variance among the ampicillin-resistant mutants was associated with different sets of target genes. About half of the resistant clones suffered large fitness deficits, and their mutations impacted major outer-membrane proteins or subunits of RNA polymerases. The other mutants experienced little or no fitness costs and with, one exception, they had mutations affecting other genes and functions. Our findings underscore the importance of comparative studies on the evolution of antibiotic resistance, and they highlight the nuanced processes that shape these phenotypes.

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Concurrent natural evolution of glyphosate resistance single- and double-point EPSPS mutations in weed species provides an opportunity for the estimation of resistance fitness benefits and prediction of equilibrium resistance frequencies in environments under glyphosate selection. Assessment of glyphosate resistance benefit was conducted for the most commonly identified single Pro-106-Ser and less-frequent double TIPS mutations in the EPSPS gene evolved in the global damaging weed Eleusine indica. Under glyphosate selection at the field dose, plants with the single Pro-106-Ser mutation at homozygous state (P106S-rr) showed reduced survival and compromised vegetative growth and fecundity compared with TIPS plants. Whereas both homozygous (TIPS-RR) and compound heterozygous (TIPS-Rr) plants with the double TIPS resistance mutation displayed similar survival rates when exposed to glyphosate, a significantly higher fecundity in the currency of seed number was observed in TIPS-Rr than TIPS-RR plants. The highest plant fitness benefit was associated with the heterozygous TIPS-Rr mutation, whereas plants with the homozygous Pro-106-Ser and TIPS mutations exhibited, respectively, 31% and 39% of the fitness benefit revealed by the TIPS-Rr plants. Populations are predicted to reach stable allelic and genotypic frequencies after 20 years of glyphosate selection at which the WT allele is lost and the stable genotypic polymorphism is comprised by 2% of heterozygous TIPS-Rr, 52% of homozygous TIPS-RR and 46% of homozygous P106S-rr. The high inbreeding nature of E. indica is responsible for the expected frequency decrease in the fittest TIPS-Rr in favour of the homozygous TIPS-RR and P106S-rr. Mutated alleles associated with the glyphosate resistance EPSPS single EPSPS Pro-106-Ser and double TIPS mutations confer contrasting fitness benefits to E. indica under glyphosate treatment and therefore are expected to exhibit contrasting evolution rates in cropping systems under recurrent glyphosate selection.

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Bacterial genomes encode various multidrug efflux pumps (MDR) whose specific conditions for fitness advantage are unknown. We show that the efflux pump MdtEF-TolC, in Escherichia coli, confers a fitness advantage during exposure to extreme acid (pH 2). Our flow cytometry method revealed pH-dependent fitness trade-offs between bile acids (a major pump substrate) and salicylic acid, a membrane-permeant aromatic acid that induces a drug resistance regulon but depletes proton motive force (PMF). The PMF drives MdtEF-TolC and related pumps such as AcrAB-TolC. Deletion of mdtE (with loss of the pump MdtEF-TolC) increased the strain's relative fitness during growth with or without salicylate or bile acids. However, when the growth cycle included a 2-h incubation at pH 2 (below the pH growth range), MdtEF-TolC conferred a fitness advantage. The fitness advantage required bile salts but was decreased by the presence of salicylate, whose uptake is amplified by acid. For comparison, AcrAB-TolC, the primary efflux pump for bile acids, conferred a PMF-dependent fitness advantage with or without acid exposure in the growth cycle. A different MDR pump, EmrAB-TolC, conferred no selective benefit during growth in the presence of bile acids. Without bile acids, all three MDR pumps incurred a large fitness cost with salicylate when exposed at pH 2. These results are consistent with the increased uptake of salicylate at low pH. Overall, we showed that MdtEF-TolC is an MDR pump adapted for transient extreme-acid exposure and that low pH amplifies the salicylate-dependent fitness cost for drug pumps. IMPORTANCE Antibiotics and other drugs that reach the gut must pass through stomach acid. However, little is known of how extreme acid modulates the effect of drugs on gut bacteria. We find that extreme-acid exposure leads to a fitness advantage for a multidrug pump that otherwise incurs a fitness cost. At the same time, extreme acid amplifies the effect of salicylate selection against multidrug pumps. Thus, organic acids and stomach acid could play important roles in regulating multidrug resistance in the gut microbiome. Our flow cytometry assay provides a way to measure the fitness effects of extreme-acid exposure to various membrane-soluble organic acids, including plant-derived nutrients and pharmaceutical agents. Therapeutic acids might be devised to control the prevalence of multidrug pumps in environmental and host-associated habitats.

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A bacterium's fitness relative to its competitors, both in the presence and absence of antibiotics, plays a key role in its ecological success and clinical impact. In this study, we examine whether tetracycline-resistant mutants are less fit in the absence of the drug than their sensitive parents, and whether the fitness cost of resistance is constant or variable across independently derived lines. Tetracycline-resistant lines suffered, on average, a reduction in fitness of almost 8%. There was substantial among-line variation in the fitness cost. This variation was not associated with the level of resistance conferred by the mutations, nor did it vary significantly across several genetic backgrounds. The two resistant lines with the most extreme fitness costs involved functionally unrelated mutations on different genetic backgrounds. However, there was also significant variation in the fitness costs for mutations affecting the same pathway and even different alleles of the same gene. Our findings demonstrate that the fitness costs of antibiotic resistance do not always correlate with the phenotypic level of resistance or the underlying genetic changes. Instead, these costs reflect the idiosyncratic effects of particular resistance mutations and the genetic backgrounds in which they occur.

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Pollen-mediated gene flow of genetically modified crops to their wild relatives can facilitate the spread of transgenes into the ecosystem and alter the fitness of the consequential progeny. A two-year field study was conducted to quantify the gene flow from glufosinate-ammonium resistant (GR) soybean (Glycinemax) to its wild relative, wild soybean (G. soja), and assess the potential weed risk of hybrids resulting from the gene flow during their entire life cycle under field conditions in Korea, where wild soybean is the natural inhabitant. Pollen-mediated gene flow from GR soybeans to wild soybeans ranged from 0.292% (mixed planting) to 0.027% at 8 m distance. The log-logistic model described the gene flow rate with increasing distance from GR soybean to wild soybean; the estimated effective isolation distance for 0.01% gene flow between GR and wild soybeans was 37.7 m. The F1 and F2 hybrids exhibited the intermediate characteristics of their parental soybeans in their vegetative and reproductive stages. Canopy height and stem length of hybrids were close to those of wild soybean, which shows an indeterminate growth; the numbers of flowers, pods, and seeds per hybrid plant were close to those of wild soybean and significantly higher than those of GR soybean. Seed longevity of F2 hybrid plants was also intermediate but significantly greater than that of GR soybean due to high seed dormancy. Our results suggest that transgenes of the GR soybean might disperse into wild populations and persist in the agroecosystem of the genetic origin regions due to the pollen-mediated gene flow and the relatively high fitness of the hybrid progeny.

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Integration of a conjugative plasmid into a bacterial chromosome can promote the transfer of chromosomal DNA to other bacteria. Intraspecies chromosomal conjugation is believed responsible for creating the global pathogens Klebsiella pneumoniae ST258 and Escherichia coli ST1193. Interspecies conjugation is also possible but little is known about the genetic architecture or fitness of such hybrids. To study this, we generated by conjugation 14 hybrids of E. coli and Salmonella enterica. These species belong to different genera, diverged from a common ancestor >100 Ma, and share a conserved order of orthologous genes with ∼15% nucleotide divergence. Genomic analysis revealed that all but one hybrid had acquired a contiguous segment of donor E. coli DNA, replacing a homologous region of recipient Salmonella chromosome, and ranging in size from ∼100 to >4,000 kb. Recombination joints occurred in sequences with higher-than-average nucleotide identity. Most hybrid strains suffered a large reduction in growth rate, but the magnitude of this cost did not correlate with the length of foreign DNA. Compensatory evolution to ameliorate the cost of low-fitness hybrids pointed towards disruption of complex genetic networks as a cause. Most interestingly, 4 of the 14 hybrids, in which from 45% to 90% of the Salmonella chromosome was replaced with E. coli DNA, showed no significant reduction in growth fitness. These data suggest that the barriers to creating high-fitness interspecies hybrids may be significantly lower than generally appreciated with implications for the creation of novel species.

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Mutations of the TP53 gene occur in a subset of patients with acute myeloid leukemia (AML) and confer an exceedingly adverse prognosis. However, whether different types of TP53 mutations exert a uniformly poor outcome has not been investigated yet. Here, we addressed this issue by analyzing data of 1537 patients intensively treated within protocols of the German-Austrian AML study group. We classified TP53 mutations depending on their impact on protein structure and according to the evolutionary action (EAp53) score and the relative fitness score (RFS). In 98/1537 (6.4%) patients, 108 TP53 mutations were detected. While the discrimination depending on the protein structure and the EAp53 score did not show a survival difference, patients with low-risk and high-risk AML-specific RFS showed a different overall survival (OS; median, 12.9 versus 5.5 months, p = 0.017) and event-free survival (EFS; median, 7.3 versus 5.2 months, p = 0.054). In multivariable analyses adjusting for age, gender, white blood cell count, cytogenetic risk, type of AML, and TP53 variant allele frequency, these differences were statistically significant for both OS (HR, 2.14; 95% CI, 1.15-4.0; p = 0.017) and EFS (HR, 1.97; 95% CI, 1.06-3.69; p = 0.033). We conclude that the AML-specific RFS is of prognostic value in patients with TP53-mutated AML and a useful tool for therapeutic decision-making.

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BACKGROUND: The house fly, Musca domestica L. (Diptera: Muscidae) is an important public health pest that serves as a carrier for pathogens transmitting various diseases of man and animals. It is well known for rapid resistance development to insecticides applied for its chemical control. Chlorantraniliprole, an anthranilic diamide, a ryanodine receptor agonist, is a promising agent for the integrated pest management of various insect pests. To design a retrospective resistance management strategy, life history traits of the chlorantraniliprole laboratory-selected (CTPR-SEL) and unselected counterpart (UNSEL) sub-populations of a field strain and their reciprocal crosses were studied. RESULTS: After eight generations of consecutive selection with chlorantraniliprole, a 750-fold resistance level when compared to a susceptible strain and a 124-fold resistance level when compared to the UNSEL strain had developed in CTPR-SEL. Very low cross resistance to bifenthrin but no cross resistance to spinosad and fipronil was observed in the CTPR-SEL strain. Results of the fitness traits suggest that the CTPR-SEL has a lower relative fitness (0.34), reduced fecundity, a decrease in eggs hatchability, lower biotic potential and net reproductive rate as compared to the UNSEL strain. Interestingly, chlorantraniliprole resistance was unstable in the CTPR-SEL. CONCLUSIONS: Fitness costs associated with chlorantraniliprole resistance suggest that the efficacy of this insecticide could be preserved for a prolonged duration of time by alternating its use with insecticides having dissimilar modes of action and no cross resistance. When cross-resistance is absent, a sequence of two insecticides is expected to be more durable than a mixture unless the population's h2 of resistance to the mixture is less than half of the mean of the population's h2 of resistance to the two individual components of the mixture. Unstable chlorantraniliprole resistance could also help to sustain its efficacy by being withdrawn from usage for some period of time. © 2019 Society of Chemical Industry.

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