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One of the longstanding puzzles of antimicrobial resistance is why the frequency of resistance persists at intermediate levels. Theoretical explanations for the lack of fixation of resistance include cryptic costs of resistance or negative frequency-dependence but are seldom explored experimentally. β -lactamases, which detoxify penicillin-related antibiotics, have well-characterized frequency-dependent dynamics driven by cheating and cooperation. However, bacterial physiology determines whether β -lactamases are cooperative, and we know little about the sociality or fitness of β -lactamase producers in infections. Moreover, media-based experiments constrain how we measure fitness and ignore important parameters such as infectivity and transmission among hosts. Here, we investigated the fitness effects of broad-spectrum AmpC β -lactamases in Enterobacter cloacae in broth, biofilms, and gut infections in a model insect. We quantified frequency- and dose-dependent fitness using cefotaxime, a third-generation cephalosporin. We predicted that infection dynamics would be similar to those observed in biofilms, with social protection extending over a wide dose range. We found evidence for the sociality of β -lactamases in all contexts with negative frequency-dependent selection, ensuring the persistence of wild-type bacteria, although cooperation was less prevalent in biofilms, contrary to predictions. While competitive fitness in gut infections and broth had similar dynamics, incorporating infectivity into measurements of fitness in infections significantly affected conclusions. Resistant bacteria had reduced infectivity, which limited the fitness benefits of resistance to infections challenged with low antibiotic doses and low initial frequencies of resistance. The fitness of resistant bacteria in more physiologically tolerant states (in biofilms, in infections) could be constrained by the presence of wild-type bacteria, high antibiotic doses, and limited availability of β -lactamases. One conclusion is that increased tolerance of β -lactams does not necessarily increase selection pressure for resistance. Overall, both cryptic fitness costs and frequency dependence curtailed the fitness benefits of resistance in this study. [ABSTRACT FROM AUTHOR]

Spodoptera littoralis (Boisd.) (Lepidoptera: Noctuidae) is a major economic pest attacking a variety of crops in Egypt and other Mediterranean countries. S. littoralis has developed resistance to both traditional and novel insecticides. The current study investigated S. littoralis resistance to indoxacarb regarding inheritance mode, realized heritability (h 2), and fitness costs. An indoxacarb-resistant strain (Indoxa-SEL) was obtained by selecting a field strain with indoxacarb. Indoxa-SEL strain outperformed the susceptible one (Indoxa-S) by 29.77-fold after 16 consecutive generations of selection. Based on the LC50 values of the progenies of reciprocal crosses F1 (R♂ × S♀) and F1ʹ (R♀ × S♂), S. littoralis resistance to indoxacarb was found to be autosomal and partially recessive. Chi-square tests for goodness-of-fit between observed and expected mortalities of self-bred F1 and resistant strain reciprocal crosses revealed that the resistance was controlled by multiple genes. The resistant strain had a relative fitness of 0.80, with significantly increased total preovipositional period of females, egg, larvae, pupae, preadult, adult, and total longevity period. The estimated realized heritability value in the Indoxa-SEL strain was 0.21. The current study will contribute to sustaining indoxacarb efficacy and designing effective resistance management programs against S. littoralis. [ABSTRACT FROM AUTHOR]

Annual indoxacarb resistance in Helicoverpa armigera (Hübner) populations collected from various crops in Australia was monitored between 2013 and 2023. Resistance frequency determined by F2 screening using a predetermined discriminating dose of indoxacarb, was lowest in the 2013–2014 and 2015–2016 seasons at 0.0164 and 0.0246, respectively. Resistance then increased significantly to a ten-year high of 0.0869 in 2018–2019 but declined to 0.0557 in 2019–2020 during a severe drought, remaining relatively stable thereafter to 2023. Indoxacarb resistance was first detected in H. armigera collected from maize in the Gwydir valley, New South Wales, in 2013 (strain GY7-39). In 2017, a second indoxacarb resistant H. armigera strain (UN1U3-10) was isolated from a population collected in chickpeas in the Liverpool Plains, New South Wales. Indoxacarb resistance of this strain was characterized to evaluate its potential to compromise the ongoing effectiveness of insecticide resistance management strategies in Australian farming systems. Survival at the discriminating dose of indoxacarb in UN1U3-10 was 28.9, 52.6, 86.7, and 92.9% in the F2, F3, F4, and F5, respectively. Following introgression with a susceptible strain and reselection with the discriminating dose of indoxacarb, the resistance ratio of UN1U3-10 was approximately 800-fold. Resistance was autosomal, incompletely dominant and conferred by more than 1 locus. While indoxacarb resistance in UN1U3-10 did not confer to emamectin benzoate or spinetoram and there was no evidence of major cross-resistance to the Bt toxins Cry1A, Cry2A or Vip3A, there was 5-fold reduced sensitivity to chlorantraniliprole. Indoxacarb resistance was suppressed by approximately 10-fold by PBO with no synergism by TPP or DEM, suggesting the involvement of cytochrome P450 enzymes. A stability analysis indicated a fitness cost may be associated with the genes that confer resistance in the UN1U3-10 strain. The potential risk for diverse indoxacarb resistance in the Australian H. armigera population is discussed. [ABSTRACT FROM AUTHOR]

Variation in gene copy number can alter gene expression and influence downstream phenotypes; thus copy-number variation provides a route for rapid evolution if the benefits outweigh the cost. We recently showed that genetic background significantly influences how yeast cells respond to gene overexpression, revealing that the fitness costs of copy-number variation can vary substantially with genetic background in a common-garden environment. But the interplay between copy-number variation tolerance and environment remains unexplored on a genomic scale. Here, we measured the tolerance to gene overexpression in four genetically distinct Saccharomyces cerevisiae strains grown under sodium chloride stress. Overexpressed genes that are commonly deleterious during sodium chloride stress recapitulated those commonly deleterious under standard conditions. However, sodium chloride stress uncovered novel differences in strain responses to gene overexpression. West African strain NCYC3290 and North American oak isolate YPS128 are more sensitive to sodium chloride stress than vineyard BC187 and laboratory strain BY4743. Consistently, NCYC3290 and YPS128 showed the greatest sensitivities to overexpression of specific genes. Although most genes were deleterious, hundreds were beneficial when overexpressed--remarkably, most of these effects were strain specific. Few beneficial genes were shared between the sodium chloride-sensitive isolates, implicating mechanistic differences behind their sodium chloride sensitivity. Transcriptomic analysis suggested underlying vulnerabilities and tolerances across strains, and pointed to natural copy-number variation of a sodium export pump that likely contributes to strain-specific responses to overexpression of other genes. Our results reveal extensive strain-by-environment interactions in the response to gene copy-number variation, raising important implications for the accessibility of copy-number variation-dependent evolutionary routes under times of stress. [ABSTRACT FROM AUTHOR]

The polyphagous pest Helicoverpa zea (Lepidoptera: Noctuidae) has evolved practical resistance to transgenic corn and cotton producing Cry1 and Cry2 crystal proteins from Bacillus thuringiensis (Bt) in several regions of the United States. However, the Bt vegetative insecticidal protein Vip3Aa produced by Bt corn and cotton remains effective against this pest. To advance knowledge of resistance to Vip3Aa, we selected a strain of H. zea for resistance to Vip3Aa in the laboratory. After 28 generations of continuous selection, the resistance ratio was 267 for the selected strain (GA-R3) relative to a strain not selected with Vip3Aa (GA). Resistance was autosomal and almost completely recessive at a concentration killing all individuals from GA. Declines in resistance in heterogeneous strains containing a mixture of susceptible and resistant individuals reared in the absence of Vip3Aa indicate a fitness cost was associated with resistance. Previously reported cases of laboratory-selected resistance to Vip3Aa in lepidopteran pests often show partially or completely recessive resistance at high concentrations and fitness costs. Abundant refuges of non-Bt host plants can maximize the benefits of such costs for sustaining the efficacy of Vip3Aa against target pests. [ABSTRACT FROM AUTHOR]

Rhopalosiphum padi is an important global wheat pest. The pyrethroid insecticide bifenthrin is widely used in the control R. padi. We explored the resistance potential, cross-resistance, adaptive costs, and resistance mechanism of R. padi to bifenthrin using a bifenthrin-resistant strain (Rp-BIF) established in laboratory. The Rp-BIF strain developed extremely high resistance against bifenthrin (1033.036-fold). Cross-resistance analyses showed that the Rp-BIF strain had an extremely high level of cross-resistance to deltamethrin (974.483-fold), moderate levels of cross-resistance to chlorfenapyr (34.051-fold), isoprocarb (27.415-fold), imidacloprid (14.819-fold), and thiamethoxam (11.228-fold), whereas negative cross-resistance was observed to chlorpyrifos (0.379-fold). The enzymatic activity results suggested that P450 played an important role in bifenthrin resistance. A super-kdr mutation (M918L) of voltage-gated sodium channel (VGSC) was found in the bifenthrin-resistant individuals. When compared with the susceptible strain (Rp-SS), the Rp-BIF strain was significantly inferior in multiple life table parameters, exhibiting a relative fitness of 0.69. Our toxicological and biochemical studies indicated that multiple mechanisms of resistance might be involved in the resistance trait. Our results provide insight into the bifenthrin resistance of R. padi and can contribute to improve management of bifenthrin-resistant R. padi in the field. [ABSTRACT FROM AUTHOR]

The Colorado potato beetle, Leptinotarsa decemlineata (Say) ([Coleoptera]: [Chrysomelidae]), is the most important defoliator of solanaceous plants worldwide. This insect displays a notorious ability in adapting to biological and synthetic insecticides, although in some cases this adaptation carries relevant fitness costs. Insecticidal gene silencing by RNA interference is a novel mode of action pesticide against L. decemlineata that is activated by ingestion of a double stranded RNA (dsRNA) targeting a vital L. decemlineata gene. We previously reported laboratory selection of a > 11,000-fold resistant strain of L. decemlineata to a dsRNA delivered topically to potato leaves. In this work, we tested the existence of fitness costs in this dsRNA-resistant colony by comparing biological parameters to the parental strain and an additional susceptible reference strain. Biological parameters included length of egg incubation period, number of eggs per clutch, egg viability, larval viability, length of larval and pupal periods, adult emergence, number of eggs laid per day, sex ratio, and adult longevity. Comparisons between the 3 beetle strains detected no fitness costs associated with resistance to dsRNA. This information is important to guide effective insect resistance management plans for dsRNA insecticides against L. decemlineata applied topically to potato leaves. [ABSTRACT FROM AUTHOR]

Certain mycophagous Drosophila species are the only known eukaryotes that can tolerate some highly potent mycotoxins. This association between mycophagy and mycotoxin tolerance is well established because Drosophila species that switch hosts from mushrooms to other food sources lose their mycotoxin tolerance trait without any evolutionary lag. These findings suggest that mycotoxin tolerance may be a costly trait to maintain. In this study, we attempted to identify whether mycotoxin tolerance has a fitness cost. Larval competitive ability is a vital fitness trait, especially in holometabolous insects, where the larvae cannot move to a new host. Furthermore, larval competitive ability is known to be associated with many critical life-history traits. Here we studied whether mycotoxin tolerance adversely affects larval competitive ability on isofemale lines from 2 distinct locations. We observed that the extent of mycotoxin tolerance affected larval competitive ability, but only in isofemale lines from one location. Additionally, we observed that the high mycotoxin-tolerant isofemale lines from the same location showed poor survival to eclosion. This study shows that mycotoxin tolerance is associated with fitness costs and provides preliminary evidence of an association between local adaptation and mycotoxin tolerance. [ABSTRACT FROM AUTHOR]

Plasmids drive bacterial evolutionary innovation by transferring ecologically important functions between lineages, but acquiring a plasmid often comes at a fitness cost to the host cell. Compensatory mutations, which ameliorate the cost of plasmid carriage, promote plasmid maintenance in simplified laboratory media across diverse plasmid–host associations. Whether such compensatory evolution can occur in more complex communities inhabiting natural environmental niches where evolutionary paths may be more constrained is, however, unclear. Here, we show a substantial fitness cost of carrying the large conjugative plasmid pQBR103 in Pseudomonas fluorescens SBW25 in the plant rhizosphere. This plasmid fitness cost could be ameliorated by compensatory mutations affecting the chromosomal global regulatory system gacA/gacS , which arose rapidly in plant rhizosphere communities and were exclusive to plasmid carriers. These findings expand our understanding of the importance of compensatory evolution in plasmid dynamics beyond simplified lab media. Compensatory mutations contribute to plasmid survival in bacterial populations living within complex microbial communities in their environmental niche. [ABSTRACT FROM AUTHOR]

The glassy-winged sharpshooter, Homalodisca vitripennis (Germar) (Hemiptera: Cicadellidae), is an important vector of bacterial Xyllela diseases throughout the southern and southwestern portions of the United States. Strong insect control measures, such that population densities of the insect vector are significantly reduced, are often necessary to limit the spread of Xylella fastidiosa. Glassy-winged sharpshooter populations within the Central Valley of California have developed a high resistance to imidacloprid (resistance ratio greater than 3,200) and tolerance to pyrethroids (ratio of less than 10) due to frequent applications of these materials. The purpose of this study was to determine the potential effects of insecticide resistance upon a variety of sharpshooter life history parameters associated with reproductive fitness. Our results indicate that individuals from susceptible populations of glassy-winged sharpshooters exhibited significantly higher fecundity and longer adult lifespans than those from the resistant populations. Additionally, resistant individuals were on average slightly larger than susceptible individuals. These results provide a strong indication that resistance to neonicotinoids imposes a reproductive fitness cost in an insecticide-free environment. [ABSTRACT FROM AUTHOR]

Fitness costs associated with insect resistance to insecticides can be exploited to implement resistance management programs. However, most of these studies are restricted to evaluating biological traits on artificial diets. Here, we investigated the fitness cost associated with chlorantraniliprole in Spodoptera frugiperda (J.E. Smith) feeding on corn, soybean, and cotton plants. We used a near-isogenic strain of S. frugiperda resistant to chlorantraniliprole (Iso-RR), a susceptible strain (SS), and heterozygotes strains (H1 and H2) to evaluate several biological and population growth parameters. Larval survival of the Iso-RR strain was on average 90% on corn, 65% on soybean, and 57% on cotton plants. Development time of the larval stage also differed among host plants, Iso-RR strain took on average 14, 17, and 26 days to reach the pupal stage on corn, soybean, and cotton plants respectively. Net reproductive rate, intrinsic rate of population increase, and finite rate of population increase were higher for Iso-RR strain feeding on corn plants than other host plants. The relative fitness, based on the intrinsic rate of population increase, of S. frugiperda resistant strain on corn, soybean, and cotton plants were 1.04, 0.85, and 0.88, respectively. Therefore, no fitness cost was observed for S. frugiperda feeding on corn plants, but a significant fitness cost was observed when this pest fed on soybean and cotton plants. We showed that the food source influences the fitness cost of S. frugiperda resistant to diamide. Such information may help to implement resistance management strategies based on each crop. Graphical Abstract [ABSTRACT FROM AUTHOR]

The fall armyworm, Spodoptera frugiperda, is an economically important pest of corn, cotton, and soybean, and a major target of transgenic crops expressing Bacillus thuringiensis (Bt) proteins. In recent years, this insect has invaded most countries in Africa, Southeastern Asia, and Oceania, posing a great threat to food security. Successful use of Bt crops in the U.S. indicates that Bt technology can be an effective tool for management of S. frugiperda in other countries. Evolution of insect resistance is the primary threat to the long-term efficacy of Bt technology. There are many factors that may affect the rate of evolution of insect resistance to Bt crops, which include initial resistance allele frequency, the dose of Bt protein in Bt crops, cross-resistance, complete/incomplete resistance, and fitness costs associated with resistance. Currently, the high dose/refuge and gene-pyramiding approaches are the two main IRM strategies used in the U.S. to combat evolution of insect resistance. In this paper, we review research on resistance of S. frugiperda to Cry1, Cry2, and Vip3Aa proteins. Specifically, we discuss the resistance allele frequencies of S. frugiperda to these three proteins in the field, the genetic basis of resistance, the patterns of cross-resistance, and the fitness costs associated with resistance. Experience and knowledge gained from these studies provide valuable information for the successful use of Bt crop technology for control of S. frugiperda worldwide. [ABSTRACT FROM AUTHOR]

The melon aphid, Aphis gossypii Glover, is an important pest on various vegetables around the world and has developed resistance to neonicotinoids in fields. Cycloxaprid is a novel cis -nitromethylene configuration neonicotinoid insecticide that is different from trans -configuration neonicotinoids like imidacloprid and thiamethoxam. Herein, the cross-resistance to the other seven insecticides and fitness costs were investigated in the cycloxaprid-resistant A. gossypii strain (Cpd-R), which has developed 69.5-fold resistance to cycloxaprid. The results showed that the Cpd-R strain had very low levels of cross-resistance to imidacloprid (4.3-fold), acetamiprid (2.9-fold), thiamethoxam (3.7-fold), nitenpyram (6.1-fold), flupyradifurone (2.2-fold), and sulfoxaflor (4.5-fold), while it exhibited a cross-resistance to dinotefuran (10.6-fold). The fitness of the Cpd-R strain by life table analysis was only 0.799 compared to the susceptible strain (Cpd-S). This Cpd-R strain exhibited significantly reduction in fecundity, oviposition days, and developmental time of nymph stage compared to the Cpd-S strain. Moreover, the expression levels of some genes related to the development and reproduction, including EcR , USP , JHAMT, and JHEH were significantly up-regulated, while Vg was down-regulated in the Cpd-R strain. This study indicates that the Cpd-R strain possessed a certain fitness cost. The above research results are useful for rational application of cycloxaprid and implementing the appropriate resistance management strategy for A. gossypii. [ABSTRACT FROM AUTHOR]

Trade-offs of antibiotic resistance evolution, such as fitness cost and collateral sensitivity (CS), could be exploited to drive evolution toward antibiotic susceptibility. Decline of resistance may occur when resistance to other drug leads to CS to the first one and when compensatory mutations, or genetic reversion of the original ones, reduce fitness cost. Here we describe the impact of antibiotic-free and sublethal environments on declining ceftazidime resistance in different Pseudomonas aeruginosa resistant mutants. We determined that decline of ceftazidime resistance occurs within 450 generations, which is caused by newly acquired mutations and not by reversion of the original ones, and that the original CS of these mutants is preserved. In addition, we observed that the frequency and degree of this decline is contingent on genetic background. Our results are relevant to implement evolution-based therapeutic approaches, as well as to redefine global policies of antibiotic use, such as drug cycling. [ABSTRACT FROM AUTHOR]

The susceptibility of Acinetobacter baumannii exposed to primary antibiotic can be either increased or decreased when exposed to secondary antibiotic. This study was designed to assess the relative fitness, collateral susceptibility and collateral resistance of polymyxin B‐ (PMB‐) adapted A. baumannii to ciprofloxacin (CIP), meropenem (MER), PMB, tetracycline (TET) and tobramycin (TOB). Strains of wild‐type A. baumannii KACC 12454 (ABKACC), wild‐type A. baumannii CCARM 12088 (ABCCARM), PMB‐adapted ABKACC, PMB‐adapted ABCCARM, stabilized ABKACC and stabilized ABCCARM were used in this study. Compared to the wild‐type ABKACC, the MICs of PMB were increased from 2 to 128 μg ml−1 against PMB‐adapted ABKACC, while MICs of CIP, MER, TET and TOB were decreased from 2 to 1 μg ml−1, 16 to 1 μg ml−1, 16 to 2 μg ml−1 and 64 to 16 μg ml−1, respectively. The PMB‐adapted ABCCARM was resistant to CIP (32 μg ml−1) and PMB (64 μg ml−1) compared to the wild‐type ABCCARM. The resistance of stabilized ABKACC and ABCCARM to all antibiotics was lost after antibiotic‐free culture in the exception of CIP and TET. The susceptibilities of wild‐type, PMB‐adapted and stabilized ABKACC and ABCCARM to CIP, MER, PMB, TET and TOB were increased in the presence of β‐lactamase and efflux pump inhibitors. The high levels of relative fitness were observed for stabilized ABKACC, PMB‐adapted ABCCARM and stabilized ABCCARM. The stabilized ABKACC and PMB‐adapted ABCCARM were highly heteroresistance to PMB and TET, respectively. The PMB‐adapted ABKACC and ABCCARM showed various antibiotic patterns, known as collateral susceptibility and collateral resistance. The results provide useful information for designing effective antibiotic regimens that can enhance the antibiotic activity against A. baumannii infections. [ABSTRACT FROM AUTHOR]

The persistence of plasmids in bacterial populations represents a puzzling evolutionary problem with serious clinical implications due to their role in the ongoing antibiotic resistance crisis. Recently, major advancements have been made toward resolving this "plasmid paradox" but mainly in a nonclinical context. Here, we propose an additional explanation for the maintenance of multidrug‐resistance plasmids in clinical Escherichia coli strains. After coevolving two multidrug‐resistance plasmids encoding resistance to last resort carbapenems with an extraintestinal pathogenic E. coli strain, we observed that chromosomal media adaptive mutations in the global regulatory systems CCR (carbon catabolite repression) and ArcAB (aerobic respiration control) pleiotropically improved the maintenance of both plasmids. Mechanistically, a net downregulation of plasmid gene expression reduced the fitness cost. Our results suggest that global chromosomal transcriptional rewiring during bacterial niche adaptation may facilitate plasmid maintenance. [ABSTRACT FROM AUTHOR]

Antibiotic resistance often generates defects in bacterial growth called fitness cost. Understanding the causes of this cost is of paramount importance, as it is one of the main determinants of the prevalence of resistances upon reducing antibiotics use. Here we show that the fitness costs of antibiotic resistance mutations that affect transcription and translation in Escherichia coli strongly correlate with DNA breaks, which are generated via transcription–translation uncoupling, increased formation of RNA–DNA hybrids (R-loops), and elevated replication–transcription conflicts. We also demonstrated that the mechanisms generating DNA breaks are repeatedly targeted by compensatory evolution, and that DNA breaks and the cost of resistance can be increased by targeting the RNase HI, which specifically degrades R-loops. We further show that the DNA damage and thus the fitness cost caused by lack of RNase HI function drive resistant clones to extinction in populations with high initial frequency of resistance, both in laboratory conditions and in a mouse model of gut colonization. Thus, RNase HI provides a target specific against resistant bacteria, which we validate using a repurposed drug. In summary, we revealed key mechanisms underlying the fitness cost of antibiotic resistance mutations that can be exploited to specifically eliminate resistant bacteria. [ABSTRACT FROM AUTHOR]

Pyrethroid insecticides have been widely utilized for insect pest control. Target-site resistance is one of the major mechanisms explaining pest resistance to pyrethroids. This study quantified pyrethroid resistance and fitness cost conferred by the voltage-gated sodium channel (VGSC) M918L mutation in Rhopalosiphum padi. Six s-kdr -SS and six s-kdr -RS parthenogenetic lineages were established from the same field population and were reared in the laboratory without exposure to pesticides for more than one year. Enzyme activity analysis demonstrated that metabolic resistance had no impact on these lineages. Bioassays showed that the M918L mutation strongly affected pyrethroid efficiency, conferring moderate resistance to bifenthrin (type I) (39.0-fold) and high resistance to lambda-cyhalothrin (type II) (194.7-fold). Compared with the life table of s-kdr -SS lineages, s-kdr -RS lineages exhibited a relative fitness cost with significant decreases in longevity and fecundity. Meanwhile, competitive fitness was measured by blending various ratios of s-kdr -SS and s-kdr -SS aphids. The results indicated that M918L-mediated resistance showed a significant fitness cost in the presence of wild aphids without insecticide pressure. The fitness cost strongly correlated with the initial resistance allele frequency. This work characterized the novel s-kdr M918L mutation in R. padi , defined its function in resistance to different types of pyrethroids, and documented that the M918L-mediated resistance has a significant fitness cost. [ABSTRACT FROM AUTHOR]

Pyrethroid resistance in the redlegged earth mite, Halotydeus destructor (Tucker), is primarily attributed to a kdr (knockdown resistance) mutation in the parasodium channel gene. To assess fitness costs associated with this resistance, adult resistant and susceptible populations were mixed in different proportions in microcosm tubs and placed in a shade-house simulating field conditions. Three separate experiments were undertaken whereby parental mites were collected from the field and offspring were followed for two to three generations. The association between fitness costs and kdr -mediated resistance was investigated by examining differences in mite numbers and changes in resistant allele frequencies across generations. In two (of the three) experiments, the population fitness measure of mites was significantly lower in microcosms containing a higher proportion of resistant individuals compared with treatments containing susceptible mites. No differences in mite fitness were observed between treatments in the third experiment; in this instance, the starting proportion of individuals homozygous for the resistant mutation was much lower (~40%) than in the other experiments (>90%). In all three experiments, a decrease in the resistant allele frequency across mite generations was observed. These findings indicate a potential deleterious pleiotropic effect of the kdr mutation on the fitness of H. destructor and have implications for resistance management strategies aimed at this important agricultural pest. Further experiments investigating fitness costs directly in the field are warranted. [ABSTRACT FROM AUTHOR]

Field-evolved resistance to Cry3Bb1 corn by western corn rootworm, Diabrotica virgifera virgifera LeConte (Colleoptera: Chrysomellidae), has been reported in field populations in Iowa, Illinois, Nebraska, and Minnesota. Inheritance and fitness costs associated with Cry3Bb1 resistance have been determined for non-diapausing laboratory strains of western corn rootworm with either laboratory-selected resistance or field-derived resistance. However, information on inheritance and fitness costs of Cry3Bb1 resistance in the diapausing field populations is lacking. In this study, we determined the inheritance of Cry3Bb1 resistance for four diapausing field strains of western corn rootworm using plant-based bioassays. We also determined the fitness costs for eight diapausing field populations in a greenhouse experiment. We found that Cry3Bb1 resistance was an autosomal trait and that the inheritance of resistance was mostly non-recessive; however, there was some variation in the dominance of Cry3Bb1 resistance. We did not find evidence of fitness costs affecting survival to adulthood, developmental rate, or adult dry mass. However, we did detect a fitness cost affecting adult size. The results of this study will add to the current understanding of field-evolved resistance to Cry3Bb1 corn by western corn rootworm and help in developing better strategies to manage resistance. [ABSTRACT FROM AUTHOR]

Western corn rootworm, Diabrotica virgifera virgifera LeConte, is a serious pest of corn and is often managed with transgenic corn producing insecticidal toxins from the bacterium Bacillus thuringiensis (Bt). This pest has developed field-evolved resistance to all commercially available Bt traits, beginning with Cry3Bb1 in 2009. Fitness costs may accompany Bt resistance, where individuals with alleles for Bt resistance have reduced fitness on non-Bt corn compared to Bt-susceptible individuals. In conjunction with non-Bt refuges, fitness costs can delay the evolution of Bt resistance. Importantly, ecological factors may affect the presence and magnitude of fitness costs. For western corn rootworm, available data suggest that fitness costs of Bt resistance may be present in some cases. Using two Cry3Bb1-resistant western corn rootworm strains (Hopkinton and Cresco), a fitness-cost experiment was performed by rearing rootworm in the absence of Bt for six generations to test for fitness costs of Cry3Bb1 resistance and the effect of larval rearing density on fitness costs. Fitness costs were detected for both strains; however, strains were still resistant to Cry3Bb1 corn at the end of the experiment. Cresco experienced a greater loss of resistance at low versus high density, but no effect of density was detected in Hopkinton. Our study shows that fitness costs can accompany Bt resistance in western corn rootworm and may be more pronounced under low larval density. Even though fitness costs were present, it appears that rootworm populations may remain resistant to Cry3Bb1 corn for years after resistance has evolved. [ABSTRACT FROM AUTHOR]

Development of insecticide resistance often changes life history traits of insect pests, because metabolic detoxification of insecticides in insect bodies requires huge energetic reserves. The brown planthopper, Nilaparvata lugens (Stål), an important insect pest of rice crop in East and Southeast Asia, has developed strong resistance to imidacloprid from mid-2000s. The aim of this study was to examine the costs of life history traits and reveal changes in energy reserves with developing imidacloprid resistance. We compared the life history traits (survival time, fecundity, developmental time, and hatchability) and total lipid content between imidacloprid-resistant and imidacloprid-susceptible (control) brown planthopper strains. As compared to the control strains, adults' survival time of the resistant females was shorter, and their fecundity was lower; the other life history traits did not differ significantly between the resistant and control strains. As the results, net reproductive rates (R 0 ) were lower in the resistant strains than in the susceptible strains. However, the amount of stored lipids was larger in resistant females than control ones. Our findings demonstrated a physiological trade-off between the development of imidacloprid resistance and the reproductive traits of brown planthopper. The imidacloprid-resistant strains are likely to store lipids for metabolic detoxification rather than consume them for reproduction. [ABSTRACT FROM AUTHOR]

Under ideal conditions, widely adopted transgenic crop pyramids producing two or more distinct insecticidal proteins from Bacillus thuringiensis (Bt) that kill the same pest can substantially delay evolution of resistance by pests. However, deviations from ideal conditions diminish the advantages of such pyramids. Here, we tested the hypothesis that changes in maturing cotton producing Cry1Ac and Cry2Ab affect evolution of resistance in Helicoverpa zea (Boddie) (Lepidoptera: Noctuidae), a pest with low inherent susceptibility to both toxins. In terminal leaves of field-grown Bt cotton, the concentration of both toxins was significantly higher for young, squaring plants than for old, fruiting plants. We used laboratory bioassays with plant material from field-grown cotton to test H. zea larvae from a strain selected for resistance to Cry1Ac in the laboratory, its more susceptible parent strain, and their F1 progeny. On young Bt cotton, no individuals survived to pupation. On old Bt cotton, survival to pupation was significantly higher for the lab-selected strain and the F1 progeny relative to the unselected parent strain, indicating dominant inheritance of resistance. Redundant killing, the extent to which insects resistant to one toxin are killed by another toxin in a pyramid, was complete on young Bt cotton, but not on old Bt cotton. No significant fitness costs associated with resistance were detected on young or old non-Bt cotton. Incorporation of empirical data into simulations indicates the observed increased selection for resistance on old Bt cotton could accelerate evolution of resistance to cotton producing Cry1Ac and Cry2Ab in H. zea. [ABSTRACT FROM AUTHOR]

House flies, Musca domestica L. (Diptera: Muscidae), are major pests at animal production facilities. Insecticides, particularly pyrethroids, have been used for control of house fly populations for more than 30 yr, but the evolution of resistance will likely jeopardize fly control efforts. A major mechanism of pyrethroid resistance in the house fly is target site insensitivity (due to mutations in the Voltage-sensitive sodium channel [ Vssc ]). Based on a survey of house fly populations in 2007 and 2008, the most common resistance allele at 2/3 of the states in the United States is kdr-his. This was unexpected given the relatively lower level of resistance this allele confers, and led to speculation that the kdr-his allele may have a minimal fitness cost in the absence of insecticide. The goal of this study was to evaluate the fitness cost of kdr-his by monitoring the changes in allele frequency over 15 generations in the absence of insecticide. In crosses with two different insecticide susceptible strains, we found that kdr-his had a significant fitness cost. The implications of these results to insecticide resistance monitoring and management are discussed. [ABSTRACT FROM AUTHOR]

Imidacloprid is a key insecticide used for controlling sucking insect pests, including the small brown planthopper (Laodelphax striatellus, Fallén) (Hemiptera: Delphacidae), an important agricultural pest of rice. A strain of L. striatellus (YN-ILR) developed 21-fold resistance when selected with imidacloprid on a susceptible YN strain. An in vitro study on piperonyl butoxide synergism indicated that enhanced detoxification mediated by cytochrome P450s contributed to imidacloprid resistance to some extent, and multiple P450 genes showed altered expression in the imidacloprid-resistantYN-ILR strain compared with the susceptibleYN strain (CYP425B1-CYP6BD10 had 1.51- to 11.45-fold higher expression, CYP4CE2-CYP4DD1V2 had 0.12- to 0.57-fold lower expression). While there were no mutations in target nicotinic acetylcholine receptor (nAChR) genes, subunits of Lsα1, Lsβ1, and Lsβ3 in the YN-ILR strain showed 3.86-, 4.39-, and 2.59-fold higher expression and Lsa8 displayed 0.38-fold lower expression than the YN strain. Moreover, 21-fold moderate imidacloprid resistance in individuals of L. striatellus did not produce a fitness cost. The findings suggest that L. striatellus has the capacity to develop resistance to imidacloprid through P450 detoxification and potential target nAChR expression changes, and moderate imidacloprid resistance was not associated with a fitness cost. [ABSTRACT FROM AUTHOR]

RNA interference is a powerful tool against corn rootworm. Adults and neonates of southern corn rootworm, Diabrotica undecimpunctata howardi Barber (Coleoptera: Chrysomelidae), were exposed to the LC50 of vATPase-A and Snf7 double-stranded RNAs (dsRNAs), and the effects on female fecundity, egg viability, male fitness as measured by sperm viability and mating capacity, larval recovery along with dry weight, and instar determination 10 d after exposure to dsRNA, were determined. Significant reductions were observed for a number of parameters in dsRNA-exposed rootworms relative to control treatments. Female fecundity and larval recovery were significantly reduced after exposure to both dsRNAs. In addition, larval dry weight and recovery of 2nd and 3rd instars along with dry weight for 3rd instars were significantly reduced after neonate exposure to vATPase-A dsRNA. Neither dsRNA affected male capacity to mate or sperm viability after exposure to the respective LC50s. After 10 d of feeding on untreated corn roots, neonates that survived exposure for 2 d to the vATPase-A dsRNA LC50 exhibited lower dry weight than the control. There was significant gene knockdown in adult males and females after exposure for 5 d to LC50 of vATPase-A and Snf7 dsRNAs. The parameters are discussed in terms of fitness and possible outcomes after deployment of corn hybrids expressing dsRNAs. [ABSTRACT FROM AUTHOR]

The house fly, Musca domestica L. (Diptera: Muscidae), is a major pest of medical and veterinary importance all over the world. Management efforts for house flies are usually compromised owing to their resistance to many groups of conventional insecticides. Cantharidin, a natural toxin produced by meloid beetles, is a biopesticide with a reported toxicity to some insect pests including house flies. However, the effects of cantharidin on biological and fitness parameters of house flies have not yet been investigated. In the present study, we investigated the toxicity and sublethal effects of cantharidin on biological parameters of house flies for two consecutive generations. The results revealed that the values of LC50, LC25, LC10, and LC2 against house flies were to be 2.45, 1.23, 0.66, and 0.30 mg/liter, respectively. Sublethal effects of these concentrations on the development and reproduction parameters of house flies revealed that cantharidin reduced population growth by affecting pupation rate, adult emergence, and by lengthening developmental time. The female ratio, fecundity, egg hatching, and survival of adult flies were significantly reduced at LC2, LC10, LC25, and LC50 of cantharidin when compared with the control group. Furthermore, the increase in concentration of cantharidin had a significant effect on reducing the mean values of mean relative growth rate, net reproductive rate (Ro), intrinsic rate of natural increase (rm), and biotic potential (bp). In conclusion, the results of this study revealed the toxicity of cantharidin against house flies and the adverse effects of sublethal concentrations on biological parameters which may have positive implications for effective management of house flies. [ABSTRACT FROM AUTHOR]

Frankliniella occidentalis (Pergande) is an economically important pest of agricultural crops. High resistance has been detected in field populations of F. occidentalis against the insecticide spinosad. In this study, we compared life history traits, body sizes, and feeding behaviors (recorded via an electrical penetration graph) of spinosad-susceptible (Ivf03) and spinosad-resistant (NIL-R) near-isogenic lines of F. occidentalis. Life table analysis showed that NIL-R had reduced female longevity and reduced fecundity. The relative fitness of NIL-R (0.43) was less than half that of Ivf03. NIL-R individuals were smaller than Ivf03 individuals, both in body length and body width at every stage. The number and duration of feeding activities were significantly reduced in NIL-R, with the exception of total duration of long-ingestion probes. These results suggest that there is a fitness trade-off associated with spinosad resistance in F. occidentalis, and that the development of resistance in this pest species may be reduced by rotating spinosad with other pesticides lacking cross-resistance. [ABSTRACT FROM AUTHOR]

Integrative and conjugative elements (ICEs) are widespread mobile DNA that transmit both vertically, in a host-integrated state, and horizontally, through excision and transfer to new recipients. Different families of ICEs have been discovered with more or less restricted host ranges, which operate by similar mechanisms but differ in regulatory networks, evolutionary origin and the types of variable genes they contribute to the host. Based on reviewing recent experimental data, we propose a general model of ICE life style that explains the transition between vertical and horizontal transmission as a result of a bistable decision in the ICE-host partnership. In the large majority of cells, the ICE remains silent and integrated, but hidden at low to very low frequencies in the population specialized host cells appear in which the ICE starts its process of horizontal transmission. This bistable process leads to host cell differentiation, ICE excision and transfer, when suitable recipients are present. The ratio of ICE bistability (i.e. ratio of horizontal to vertical transmission) is the outcome of a balance between fitness costs imposed by the ICE horizontal transmission process on the host cell, and selection for ICE distribution (i.e. ICE 'fitness'). From this emerges a picture of ICEs as elements that have adapted to a mostly confined life style within their host, but with a very effective and dynamic transfer from a subpopulation of dedicated cells. [ABSTRACT FROM AUTHOR]

Mosquitoes are known to be vectors of numerous diseases leading to human morbidity and mortality at large scale in the world. Insecticide resistance has become a serious concern in controlling the insect vectors of public health importance. Dimethoate is an organophosphate insecticide used to control different insect pests including mosquitoes. Biological parameters of susceptible, unselected, and dimethoate-selected strains of Culex quinquefasciatus Say were studied in the laboratory to recognize resistance development potential and associated fitness cost. The dimethoate-selected strain showed 66.48-fold resistance to dimethoate compared with the susceptible strain after three continuous selections of generations. Realized heritability estimates of dimethoate resistance in Cx. quinquefasciatus yielded a value of 0.19. In dimethoate-selected strain, the biological traits including larval weight, survival from first instar to pupae, fecundity, number of next-generation larvae, relative fitness, net reproductive rate, intrinsic rate of natural increase, and biotic potential were significantly reduced as compared with the unselected strain. However, adult longevity, mean relative growth rate, weight of egg raft, female ratio, pupal duration, and emergence rate of the dimethoate-selected strain did not differ significantly compared with that of the unselected strain. This study provides useful information to devise retrospective management strategy for dimethoate resistance in Cx. quinquefasciatus. [ABSTRACT FROM AUTHOR]

The Phenacoccus solenopsis Tinsley (Homoptera: Pseudococcidae) is a major agricultural and horticultural pest of crops throughout the world. To develop a better resistance management strategy for P. solenopsis, we conducted a study on life history parameters of different populations of this pest, one selected with spirotetramat (Spiro-SEL), an unselected (UNSEL) population, and their reciprocal crosses. We also studied the cross-resistance and the stability of spirotetramat resistance. The Spiro-SEL of P. solenopsis exhibited a 328.69-fold resistance compared to the susceptible population (Lab-PK). The Spiro-SEL population also displayed a moderate level of cross-resistance to profenofos and bifenthrin and a high level of cross-resistance to abamectin. Resistance to spirotetramat in Spiro-SEL was unstable in the absence of selection. The study of life history parameters showed that there was a significant reduction in fitness parameters of Spiro-SEL population with a relative fitness value of 0.14. There was a significant decrease in survival rate, pupal weight, fecundity, egg hatching percentage, male and female generation time, intrinsic rate of population increase of males and females, biotic potential, and mean relative growth rate. It is concluded that selection with spirotetramat had marked effect on resistance development in P. solenopsis and upon removal of selection pressure spirotetramat resistance declined significantly, indicating unstable resistance. Development of resistance led to high fitness costs for the spirotetramat-selected population. Our study may provide the basic information on spirotetramat resistance and its mechanism to help develop the resistance management strategies. [ABSTRACT FROM AUTHOR]

Parasites and competitors are important for regulating pathogen densities and subsequent disease dynamics. It is, however, unclear to what extent this is driven by ecological and evolutionary processes. Here, we used experimental evolution to study the eco-evolutionary feedbacks among Ralstonia solanacearum bacterial pathogen, Ralstonia-specific phage parasite, and Bacillus amyloliquefaciens competitor bacterium in the laboratory and plant rhizosphere. We found that while the phage had a small effect on pathogen densities on its own, it considerably increased the R. solanacearum sensitivity to antibiotics produced by B. amyloliquefaciens. Instead of density effects, this synergy was due to phage-driven increase in phage resistance that led to trade-off with the resistance to B. amyloliquefaciens antibiotics. While no evidence was found for pathogen resistance evolution to B. amyloliquefaciens antibiotics, the fitness cost of adaptation (reduced growth) was highest when the pathogen had evolved in the presence of both parasite and competitor. Qualitatively similar patterns were found between laboratory and greenhouse experiments even though the evolution of phage resistance was considerably attenuated in the tomato rhizosphere. These results suggest that evolutionary trade-offs can impose strong constraints on disease dynamics and that combining phages and antibiotic-producing bacteria could be an efficient way to control agricultural pathogens. [ABSTRACT FROM AUTHOR]

Fisher's geometrical model (FGM) has been widely used to depict the fitness effects of mutations. It is a general model with few underlying assumptions that gives a large and comprehensive view of adaptive processes. It is thus attractive in several situations, for example adaptation to antibiotics, but comes with limitations, so that more mechanistic approaches are often preferred to interpret experimental data. It might be possible however to extend FGM assumptions to better account for mutational data. This is theoretically challenging in the context of antibiotic resistance because resistance mutations are assumed to be rare. In this article, we show with Escherichia coli how the fitness effects of resistance mutations screened at different doses of nalidixic acid vary across a dose-gradient. We found experimental patterns qualitatively consistent with the basic FGM (rate of resistance across doses, gamma distributed costs) but also unexpected patterns such as a decreasing mean cost of resistance with increasing screen dose. We show how different extensions involving mutational modules and variations in trait covariance across environments, can be discriminated based on these data. Overall, simple extensions of the FGM accounted well for complex mutational effects of resistance mutations across antibiotic doses. [ABSTRACT FROM AUTHOR]

Antipredator responses often involve changes in several phenotypic traits and these changes interactively influence fitness. However, gaining insight into how the overall fitness effect of the overall response comes about is notoriously difficult. One promising avenue is to manipulate a single defensive trait and observe how that modifies fitness as well as the expression of other inducible responses. In chemically-defended animals, toxins are likely to be costly to produce but it is still unknown how their depletion influences other characteristics. In the present study, we artificially depleted bufadienolide toxin stores in common toad ( Bufo bufo) tadpoles, and assessed the effect of this with respect to the interaction with predator presence and limited food availability. We found that toxin depletion in tadpoles did not significantly affect any of the measured life-history traits. Tadpoles in the predator treatment exhibited an elevated development rate, although this was only apparent when food availability was limited. Also, body mass at metamorphosis was lower in tadpoles exposed to chemical cues indicating a predation threat and when food availability was limited. These results provide evidence that, in larval common toads, the expression of inducible defences may incur fitness costs, whereas chemical defences are either expressed constitutively or, if inducible, elevated toxin production has negligible costs. [ABSTRACT FROM AUTHOR]

Transgenic Bacillus thuringiensis (Bt) crops are increasingly significant in pest control, but resistance development of target pests is a major issue in the sustainable deployment of Bt crops. The fitness cost of resistance in target pests is regarded as one of the main factors delaying resistance when adopting the refuge strategy. In this study, we compared the life-history traits of three independent sets of Helicoverpa armigera (Hübner, 1809) adults, of each there were a susceptible population and a Cry1Ac-resistant population derived by selection from it. Confirming to the previous studies, resistant individuals exhibited fewer progeny, less fecundity, lower egg hatching rate, and longer adult longevity. And poor fecundity in resistant strains was associated with the decline of the mature follicular amount, the ovarian weight ratio, and the length of the longest ovarian tubule. Interestingly, the juvenile hormone (JH) level appeared higher in resistant strains relative to susceptible strains. Application of methoprene (JH analogue) in vivo was effective in reducing fecundity and hatchability with the up-regulation of detected JH titer. These results suggested that resistance against Bt toxin reduced the reproductive capacity of H. armigera, and JH level is affected in the tradeoff between reproductive capacity and Bt resistance. [ABSTRACT FROM AUTHOR]

Although fitness costs associated with plant defensive traits are widely expected, they are not universally detected, calling into question their generality. Here, we examine the potential for life-history trade-offs associated with herbicide resistance by examining seed germination, root growth, and above-ground growth across 43 naturally occurring populations of Ipomoea purpurea that vary in their resistance to RoundUp ®, the most commonly used herbicide worldwide. We find evidence for life-history trade-offs associated with all three traits; highly resistant populations had lower germination, shorter roots, and smaller above-ground size. A visual exploration of the data indicated that the type of trade-off may differ among populations. Our results demonstrate that costs of adaptation may be present at stages other than simply the production of progeny in this agricultural weed. Additionally, the cumulative effect of costs at multiple life cycle stages can result in severe consequences to fitness when adapting to novel environments. [ABSTRACT FROM AUTHOR]

The evolutionary equilibrium hypothesis was proposed to explain variation in egg rejection rates among individual hosts (intra- and interspecific) of avian brood parasites. Hosts may sometimes mistakenly reject own eggs when they are not parasitized (i.e. make recognition errors). Such errors would incur fitness costs and could counter the evolution of host defences driven by costs of parasitism (i.e. creating equilibrium between acceptors and rejecters within particular host populations). In the present study, we report the disappearance of host eggs from nonparasitized nests in populations of seven actual and potential hosts of the common cuckoo Cuculus canorus. Based on these data, we calculate the magnitude of the balancing parasitism rate provided that all eggs lost are a result of recognition errors. Importantly, because eggs are known to disappear from nests for reasons other than erroneous host rejection, our data represent the maximum estimates of such costs. Nonetheless, the disappearance of eggs was a rare event and therefore incurred low costs compared to the high costs of parasitism. Hence, costs as a result of recognition errors are probably of minor importance with respect to opposing selective pressure for the evolution of egg rejection in these hosts. We cannot exclude the possibility that low or intermediate egg rejection rates in some host populations may be caused by spatiotemporal variation in the occurrence of parasitism and gene flow, creating a variable influence of opposing costs as a result of recognition errors and the costs of parasitism. [ABSTRACT FROM AUTHOR]

High levels of resistance to phosphine in the rice weevil Sitophilus oryzae have been detected in Asian countries including China and Vietnam, however there is limited knowledge of the genetic mechanism of resistance in these strains. We find that the genetic basis of strong phosphine resistance is conserved between strains of S. oryzae from China, Vietnam, and Australia. Each of 4 strongly resistant strains has an identical amino acid variant in the encoded dihydrolipoamide dehydrogenase (DLD) enzyme that was previously identified as a resistance factor in Rhyzopertha dominica and Tribolium castaneum. The unique amino acid substitution, Asparagine > Threonine (N505T) of all strongly resistant S. oryzae corresponds to the position of an Asparagine > Histidine variant (N506H) that was previously reported in strongly resistant R. dominica. Progeny (F16 and F18) from 2 independent crosses showed absolute linkage of N505T to the strong resistance phenotype, indicating that if N505T was not itself the resistance variant that it resided within 1 or 2 genes of the resistance factor. Non-complementation between the strains confirmed the shared genetic basis of strong resistance, which was supported by the very similar level of resistance between the strains, with LC50 values ranging from 0.20 to 0.36 mg L-1 for a 48-h exposure at 25 °C. Thus, the mechanism of high-level resistance to phosphine is strongly conserved between R. dominica, T. castaneum and S. oryzae. A fitness cost associated with strongly resistant allele was observed in segregating populations in the absence of selection. [ABSTRACT FROM AUTHOR]

Background: The projected long-term prevalence of multidrug-resistant (MDR) tuberculosis depends upon the relative fitness of MDR Mycobacterium tuberculosis strains, compared with non-MDR strains. While many experimental models have tested the in vitro or in vivo fitness costs of various drug resistance mutations, fewer epidemiologic studies have attempted to validate these experimental findings.Methods: We performed a case-control study comparing drug resistance-associated mutations from MDR M. tuberculosis strains causing multiple cases in a household to matched MDR strains without evidence of secondary household cases.Results: Eighty-eight multiple-case and 88 single-case household MDR strains were analyzed for 10 specific drug resistance-associated polymorphisms previously associated with fitness effects. We found that the isoniazid-resistant katG Ser315Thr mutation occurred more than twice as frequently in multiple-case households than in single-case households (odds ratio [OR], 2.39; 95% confidence interval [CI], 1.21-4.70), corroborating previous experimental findings. However, strains carrying both the katG Ser315Thr mutation and the rpsL Lys43Arg mutation were less likely to be found in multiple-case households (OR, 0.09; 95% CI, .01-.73), suggesting a negative epistatic interaction which contrasts previous findings.Conclusions: The case-control design presents a useful approach for assessing in vivo fitness effects of drug resistance mutations. [ABSTRACT FROM AUTHOR]

The fitness cost of antibiotic resistance is a key parameter in determining the evolutionary success of resistant bacteria. Studies of the effect of antibiotic resistance on bacterial fitness are heavily biased toward target alterations. Here we investigated how the costs in the form of a severely impaired growth rate associated with resistance due to absence of two major outer membrane porins can be genetically compensated. We performed an evolution experiment with 16 lineages of a double mutant of Escherichia coli with the ompCF genes deleted, and reduced fitness and increased resistance to different classes of antibiotics, including the carbapenems ertapenem and meropenem. After serial passage for only 250 generations, the relative growth rate increased from 0.85 to 0.99 (susceptible wild type set to 1.0). Compensation of the costs followed two different adaptive pathways where upregulation of expression of alternative porins bypassed the need for functional OmpCF porins. The first compensatory mechanism involved mutations in the phoR and pstS genes, causing constitutive high-level expression of the PhoE porin. The second mechanism involved mutations in the hfq and chiX genes that disrupted Hfq-dependent small RNA regulation, causing overexpression of the ChiP porin. Although susceptibility was restored in compensated mutants with PhoE overexpression, evolved mutants with high ChiP expression maintained the resistance phenotype. Our findings may explain why porin composition is often altered in resistant clinical isolates and provide new insights into how bypass mechanisms may allow genetic adaptation to a common multidrug resistance mechanism. [ABSTRACT FROM AUTHOR]

This article investigates the possible existence of mechanisms counterbalancing the negative pleiotropic effects on development and reproduction that are conferred by alleles responsible for herbicide resistance in the weed Alopecurus myosuroides. We considered three herbicide-resistant, mutant acetyl-coenzyme A carboxylase (ACCase) alleles, Leu1781, Asn2041, and Gly2078, found in eight resistant populations. Of these, Gly2078 is the only allele with a known fitness cost. We compared plants homozygous for wild-type ACCase alleles that were siblings of plants carrying a given mutant resistant ACCase allele with plants from three populations where resistance did not evolve. In each of two series of experiments, we measured germination dynamics, seedling vigor, plant height, vegetative biomass, and seed production. The wild-type siblings of plants carrying Gly2078 performed better in the field, on average, than wild-type plants that were sibling of plants carrying other mutant ACCase alleles, and particularly those carrying Leu1781. We propose that rapid evolution of the genetic background of plants from the populations where the Gly2078 allele originally arose could partially counterbalance Gly2078 fitness cost, enhancing the spread of the resistant genotypes. [ABSTRACT FROM AUTHOR]

Gene duplications have long been advocated to contribute to the evolution of new functions. The role of selection in their early spread is more controversial. Unless duplications are favored for a direct benefit of increased expression, they are likely detrimental. In this article, we investigated the case of duplications favored because they combine already functionally divergent alleles. Their gene-dosage/fitness relations are poorly known because selection may operate on both overall expression and duplicates relative dosage. Using the well-documented case of Culex pipiens resistance to insecticides, we compared strains with various ace-1 allele combinations, including two duplicated alleles carrying both susceptible and resistant copies. The overall protein activity was nearly additive, but, surprisingly, fitness correlated better with the relative proportion of susceptible and resistant copies rather than any absolute measure of activity. Gene dosage is thus crucial, duplications stabilizing a 'heterozygote' phenotype. It corroborates the view that these were favored because they fix a permanent heterosis, thereby solving the irreducible trade-off between resistance and synaptic transmission. Moreover, we showed that the contrasted successes of the two duplicated alleles in natural populations depend on genetic changes unrelated to ace-1, confirming the probable implication of recessive sublethal mutations linked to structural rearrangements in some duplications. [ABSTRACT FROM AUTHOR]

Objectives The objective of this study was to identify the mechanism responsible for the horizontal transfer of transposon Tn2010 in Streptococcus pneumoniae, and the genomic alterations introduced by the transfer process. Methods Tn2010 was identified using PCR in 15 clinical isolates of S. pneumoniae with erythromycin resistance. S. pneumoniae and Enterococcus faecalis isolates were used as recipient cells in mating and transformation experiments to test the conjugative transferability and transformability of Tn2010. Whole-genome sequencing was used to assess the effects of the Tn2010 transfer on recipient genomes. The biological cost of the horizontal acquisition of Tn2010 and additional genomic changes was investigated by growth competition experiments. Results Tn2010 was transformed at a frequency of 3 × 10−7 transformants per cfu, whereas no transconjugants were detected using S. pneumoniae or E. faecalis as recipient cells. Genome analysis showed that many other recombinations were scattered throughout the genome of the transformants in addition to transposon Tn2010. The transformants demonstrated a negligible fitness cost compared with the wild-type strain. Conclusions Tn2010 tended to be transferred by transformation rather than conjugation in S. pneumoniae, and the spread of Tn2010 could have a profound effect on the evolution of the genome. The acquisition of Tn2010 with negligible fitness cost may facilitate spread of the transposon. [ABSTRACT FROM PUBLISHER]

An important mechanism for generation of new genes is by duplication-divergence of existing genes. Duplication-divergence includes several different submodels, such as subfunctionalization where after accumulation of neutral mutations the original function is distributed between two partially functional and complementary genes, and neofunctionalization where a new function evolves in one of the duplicated copies while the old function is maintained in another copy. The likelihood of these mechanisms depends on the longevity of the duplicated state, which in turn depends on the fitness cost and genetic stability of the duplications. Here, we determined the fitness cost and stability of defined gene duplications/amplifications on a low copy number plasmid. Our experimental results show that the costs of carrying extra gene copies are substantial and that each additional kilo base pairs of DNA reduces fitness by approximately 0.15%. Furthermore, gene amplifications are highly unstable and rapidly segregate to lower copy numbers in absence of selection. Mathematical modeling shows that the fitness costs and instability strongly reduces the likelihood of both sub- and neofunctionalization, but that these effects can be offset by positive selection for novel beneficial functions. [ABSTRACT FROM PUBLISHER]

Destabilization of a protein impairs its metabolic efficiency. It is less clear how often destabilization also results in a gain of toxicity. We derived collections of temperature-sensitive, and thus structurally unstable, mutants of the yeast ADE2 and LYS2 genes by introducing single or very few amino acids substitutions. Overexpression of these mutant proteins led to a common, although unequal, fitness decrease. Interestingly, although the mutant proteins were functionally redundant, higher expression levels were associated with higher fitness. This result suggests that growth was hampered not by the accumulation of damaged chains but by the activities needed to remove them or by the damage caused before they were removed. Our results support the idea that any protein can become toxic when destabilized by a point mutation. [ABSTRACT FROM PUBLISHER]

Increasing adoption of transgenic crops expressing cry toxin genes from Bacillus thuringieusis (Bt crops) represents an augmented risk for development of insect resistance. While fitness costs can greatly influence the rate of resistance evolution, most available data related to Bt resistance have been obtained from laboratory-selected insect strains. In this article, we test the existence of fitness costs associated with high levels of field-evolved resistance to Bt maize event TC1507 in a strain of Spodoptera frugiperda (JE Smith) originated from maize fields in Puerto Rico. Fitness costs in resistant S. frugiperda were evaluated by comparing biological performance to susceptible insects when reared on meridic diet, maize or soybean leaf tissue, or cotton reproductive tissues. Parameters monitored included larval survival, larval and pupal weights, developmental time (larval and pupal), adult longevity, reproductive traits (fecundity and fertility), and sex ratio. We found that all monitored parameters were influenced to a similar extent by the host, independently of susceptibility to Bt maize. The only parameter that significantly differed between strains for all hosts was a longer larval developmental period in resistant S. frugiperda, which resulted in emergence asynchrony between susceptible and resistant adults. To test the relevance of fitness costs in resistant S. frugiperda, we performed a selection experiment to monitor the stability of resistance in a heterogeneous strain through 12 generations of rearing on meridic diet. Our data demonstrate lack of fitness costs relevant to stability of field-evolved resistance to Bt maize and help explain reported stability of field-evolved resistance in Puerto Rican populations of S. frugiperda. [ABSTRACT FROM AUTHOR]

Drug-resistant pathogens emerge faster than new drugs come out of drug discovery pipelines. Current and future drug options should therefore be better protected, requiring a clear understanding of the factors that contribute to the natural history of drug resistance. Although many of these factors are relatively well understood for most bacteria, this proves to be more complex for vectorborne parasites. In this review, we discuss considering three key models ( Plasmodium, Leishmania and Schistosoma) how drug resistance can emerge, spread and persist. We demonstrate a multiplicity of scenarios, clearly resulting from the biological diversity of the different organisms, but also from the different modes of action of the drugs used, the specific within- and between-host ecology of the parasites, and environmental factors that may have direct or indirect effects. We conclude that integrated control of drug-resistant vectorborne parasites is not dependent upon chemotherapy only, but also requires a better insight into the ecology of these parasites and how their transmission can be impaired. [ABSTRACT FROM AUTHOR]

An increasing trend in use of tracking devices such as geolocators is based on the assumption that the information gathered from such devices provides reliable information about the migratory behavior of free-living birds. This underlying assumption is rarely tested, as evidenced by the absence in many studies of controls, in particular treated controls, and so far never with a reasonable statistical power. Published studies have shown reduced survival prospects or delayed breeding in some species, suggesting that there may be reason to doubt that tracking devices provide unbiased information. Therefore, we conducted a meta-analysis of studies applying geolocators to wild birds to determine whether geolocators affected fitness components. Geolocators had an overall negative effect on fitness components, in particular survival, and ecological variables. Effect size was larger for aerial foragers than for other species. Moreover the leg band attachment method was more detrimental for birds than the leg-loop backpack harness. A meta-regression model of effect size showed independent negative effects of geolocators on aerial foragers, smaller species, species with smaller migration distances and in studies where geolocators were attached with a ring. These results suggest that geolocator studies should be interpreted with caution, but also raise questions whether it is ethically defensible to use geolocators on aerial foragers or small species without carrying out robust pilot studies. [ABSTRACT FROM AUTHOR]

Objectives To investigate the influence of plasmid-borne β-lactamases on the evolution of spontaneous carbapenem resistance in Escherichia coli and the fitness costs associated with resistance. Methods Stepwise selection of carbapenem-resistant mutants with or without the extended-spectrum β-lactamase (ESBL)-encoding plasmid pUUH239.2 was performed. Mutation rates and mutational pathways to resistance were determined. In vitro-selected and constructed mutants were characterized regarding the MICs of the carbapenems, porin expression profiles, growth rates and the presence of mutations in the porins ompC/ompF and their regulatory genes. The influence of the plasmid-encoded β-lactamases TEM-1, OXA-1 and CTX-M-15 on resistance development was determined. Results Results show that E. coli readily developed reduced carbapenem susceptibility and clinical resistance levels by a combination of porin loss and increased β-lactamase expression, especially towards ertapenem. All tested β-lactamases (CTX-M-15, TEM-1 and OXA-1) contributed to reduced carbapenem susceptibility in the absence of porin expression. However, complete loss of porin expression conferred a 20% fitness cost on the bacterial growth rate. Increased β-lactamase expression through spontaneous gene amplification on the plasmid was a major resistance factor. Conclusions Plasmid-encoded β-lactamases, including non-ESBL enzymes, have a strong influence on the frequency and resistance level of spontaneous carbapenem-resistant mutants. The fitness cost associated with the loss of OmpC/OmpF in E. coli most likely reduces the survivability of porin mutants and could explain why they have not emerged as a clinical problem in this species. [ABSTRACT FROM PUBLISHER]

Many autonomously replicating genetic elements exist as multiple copies within the cell. The copy number of these elements is often assumed to have important fitness consequences for both element and host, yet the forces shaping its evolution are not well understood. The 2 μm is a multicopy plasmid of Saccharomyces yeasts, encoding just four genes that are solely involved in plasmid replication. One simple model for the fitness relationship between yeasts and 2 μm is that plasmid copy number evolves as a trade-off between selection for increased vertical transmission, favouring high copy number, and selection for decreased virulence, favouring low copy number. To test this model, we experimentally manipulated the copy number of the plasmid and directly measured the fitness cost, in terms of growth rate reduction, associated with high plasmid copy number. We find that the fitness burden imposed by the 2 μm increases with plasmid copy number, such that each copy imposes a fitness burden of 0.17% (± 0.008%), greatly exceeding the cost expected for it to be stably maintained in yeast populations. Our results demonstrate the crucial importance of copy number in the evolution of yeast per 2 μm associations and pave the way for future studies examining how selection can shape the cost of multicopy elements. [ABSTRACT FROM AUTHOR]