RESUMEN
Antimicrobial resistance poses an escalating global threat, rendering traditional drug development approaches increasingly ineffective. Thus, novel alternatives to antibiotic-based therapies are needed. Exploiting pathogen cooperation as a strategy for combating resistant infections has been proposed but lacks experimental validation. Empirical findings demonstrate the successful invasion of cooperating populations by non-cooperating cheats, effectively reducing virulence in vitro and in vivo. The idea of harnessing cooperative behaviours for therapeutic benefit involves exploitation of the invasive capabilities of cheats to drive medically beneficial traits into infecting populations of cells. In this study, we employed Pseudomonas aeruginosa quorum sensing cheats to drive antibiotic sensitivity into both in vitro and in vivo resistant populations. We demonstrated the successful invasion of cheats, followed by increased antibiotic effectiveness against cheat-invaded populations, thereby establishing an experimental proof of principle for the potential application of the Trojan strategy in fighting resistant infections.
Asunto(s)
Antibacterianos , Infecciones por Pseudomonas , Pseudomonas aeruginosa , Percepción de Quorum , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/fisiología , Pseudomonas aeruginosa/crecimiento & desarrollo , Antibacterianos/farmacología , Percepción de Quorum/efectos de los fármacos , Infecciones por Pseudomonas/microbiología , Infecciones por Pseudomonas/tratamiento farmacológico , Animales , Virulencia/efectos de los fármacos , Farmacorresistencia Bacteriana , Humanos , Ratones , Pruebas de Sensibilidad Microbiana , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismoRESUMEN
The growth and success of many bacteria appear to rely on a stunning range of cooperative behaviours. But what is cooperation and how is it studied?
Asunto(s)
Altruismo , Conducta Cooperativa , Evolución Biológica , Bacterias/genéticaRESUMEN
Obligately multicellular organisms, where cells can only reproduce as part of the group, have evolved multiple times across the tree of life. Obligate multicellularity has only evolved when clonal groups form by cell division, rather than by cells aggregating, as clonality prevents internal conflict. Yet obligately multicellular organisms still vary greatly in 'multicellular complexity' (the number of cells and cell types): some comprise a few cells and cell types, while others have billions of cells and thousands of types. Here, we test whether variation in multicellular complexity is explained by two conflict-suppressing mechanisms, namely a single-cell bottleneck at the start of development, and a strict separation of germline and somatic cells. Examining the life cycles of 129 lineages of plants, animals, fungi and algae, we show using phylogenetic comparative analyses that an early segregation of the germline stem-cell lineage is key to the evolution of more cell types, driven by a strong correlation in the Metazoa. By contrast, the presence of a strict single-cell bottleneck was not related to either the number of cells or the number of cell types, but was associated with early germline segregation. Our results suggest that segregating the germline earlier in development enabled greater evolutionary innovation, although whether this is a consequence of conflict reduction or other non-conflict effects, such as developmental flexibility, is unclear.
Asunto(s)
Cognición , Células Madre , Animales , Filogenia , División CelularRESUMEN
Pathogenic bacteria respond to antibiotic pressure with the evolution of resistance but survival can also depend on their ability to tolerate antibiotic treatment, known as tolerance. While a variety of resistance mechanisms and underlying genetics are well characterized in vitro and in vivo, an understanding of the evolution of tolerance, and how it interacts with resistance in situ is lacking. We assayed for tolerance and resistance in isolates of Pseudomonas aeruginosa from chronic cystic fibrosis lung infections spanning up to 40 years of evolution, with 3 clinically relevant antibiotics: meropenem, ciprofloxacin, and tobramycin. We present evidence that tolerance is under positive selection in the lung and that it can act as an evolutionary stepping stone to resistance. However, by examining evolutionary patterns across multiple patients in different clone types, a key result is that the potential for an association between the evolution of resistance and tolerance is not inevitable, and difficult to predict.
RESUMEN
Antimicrobial resistance poses an escalating global threat, rendering traditional drug development approaches increasingly ineffective. Thus, novel alternatives to antibiotic-based therapies are needed. Exploiting pathogen cooperation as a strategy for combating resistant infections has been proposed but lacks experimental validation. Empirical findings demonstrate the successful invasion of cooperating populations by non-cooperating cheats, effectively reducing virulence in vitro and in vivo. The idea of harnessing cooperative behaviors for therapeutic benefit involves exploitation of the invasive capabilities of cheats to drive medically beneficial traits into infecting populations of cells. In this study, we employed Pseudomonas aeruginosa quorum sensing cheats to drive antibiotic sensitivity into both in vitro and in vivo resistant populations. We demonstrated the successful invasion of cheats, followed by increased antibiotic effectiveness against cheat-invaded populations, thereby establishing an experimental proof of principle for the potential application of the Trojan strategy in fighting resistant infections.
RESUMEN
For infections to be maintained in a population, pathogens must compete to colonize hosts and transmit between them. We use an experimental approach to investigate within-and-between host dynamics using the pathogen Pseudomonas aeruginosa and the animal host Caenorhabditis elegans. Within-host interactions can involve the production of goods that are beneficial to all pathogens in the local environment but susceptible to exploitation by non-producers. We exposed the nematode host to 'producer' and two 'non-producer' bacterial strains (specifically for siderophore production and quorum sensing), in single infections and coinfections, to investigate within-host colonization. Subsequently, we introduced infected nematodes to pathogen-naive populations to allow natural transmission between hosts. We find that producer pathogens are consistently better at colonizing hosts and transmitting between them than non-producers during coinfection and single infection. Non-producers were poor at colonizing hosts and between-host transmission, even when coinfecting with producers. Understanding pathogen dynamics across these multiple levels will ultimately help us predict and control the spread of infections, as well as contribute to explanations for the persistence of cooperative genotypes in natural populations.
Asunto(s)
Bacterias , Coinfección , Animales , Percepción de Quorum , Caenorhabditis elegans/microbiología , Pseudomonas aeruginosa/genética , Coinfección/microbiologíaRESUMEN
Metazoans function as individual organisms but also as "colonies" of cells whose single-celled ancestors lived and reproduced independently. Insights from evolutionary biology about multicellular group formation help us understand the behavior of cells: why they cooperate, and why cooperation sometimes breaks down. Current explanations for multicellularity focus on two aspects of development which promote cooperation and limit conflict among cells: a single-cell bottleneck, which creates organisms composed of clones, and a separation of somatic and germ cell lineages, which reduces the selective advantage of cheating. However, many obligately multicellular organisms thrive with neither, creating the potential for within-organism conflict. Here, we argue that the prevalence of such organisms throughout the Metazoa requires us to refine our preconceptions of conflict-free multicellularity. Evolutionary theory must incorporate developmental mechanisms across a broad range of organisms-such as unusual reproductive strategies, totipotency, and cell competition-while developmental biology must incorporate evolutionary principles. To facilitate this cross-disciplinary approach, we provide a conceptual overview from evolutionary biology for developmental biologists, using analogous examples in the well-studied social insects.
Asunto(s)
Evolución Biológica , Linaje de la Célula , Insectos , Animales , Células Clonales , Biología Evolutiva , Insectos/crecimiento & desarrollo , ReproducciónRESUMEN
Horizontal gene transfer via plasmids could favour cooperation in bacteria, because transfer of a cooperative gene turns non-cooperative cheats into cooperators. This hypothesis has received support from theoretical, genomic and experimental analyses. By contrast, we show here, with a comparative analysis across 51 diverse species, that genes for extracellular proteins, which are likely to act as cooperative 'public goods', were not more likely to be carried on either: (1) plasmids compared to chromosomes; or (2) plasmids that transfer at higher rates. Our results were supported by theoretical modelling which showed that, while horizontal gene transfer can help cooperative genes initially invade a population, it has less influence on the longer-term maintenance of cooperation. Instead, we found that genes for extracellular proteins were more likely to be on plasmids when they coded for pathogenic virulence traits, in pathogenic bacteria with a broad host-range.
Asunto(s)
Bacterias , Transferencia de Gen Horizontal , Bacterias/genética , Especificidad del Huésped , Plásmidos/genéticaRESUMEN
Individuals are expected to avoid mating with relatives as inbreeding can reduce offspring fitness, a phenomenon known as inbreeding depression. This has led to the widespread assumption that selection will favour individuals that avoid mating with relatives. However, the strength of inbreeding avoidance is variable across species and there are numerous cases where related mates are not avoided. Here we test if the frequency that related males and females encounter each other explains variation in inbreeding avoidance using phylogenetic meta-analysis of 41 different species from six classes across the animal kingdom. In species reported to mate randomly with respect to relatedness, individuals were either unlikely to encounter relatives, or inbreeding had negligible effects on offspring fitness. Mechanisms for avoiding inbreeding, including active mate choice, post-copulatory processes and sex-biased dispersal, were only found in species with inbreeding depression. These results help explain why some species seem to care more about inbreeding than others: inbreeding avoidance through mate choice only evolves when there is both a risk of inbreeding depression and related sexual partners frequently encounter each other.
Asunto(s)
Depresión Endogámica , Preferencia en el Apareamiento Animal , Animales , Copulación , Femenino , Humanos , Endogamia , Masculino , Filogenia , Reproducción , Conducta Sexual AnimalRESUMEN
In many species that raise young in cooperative groups, breeders live an exceptionally long time despite high investment in offspring production. How is this possible given the expected trade-off between survival and reproduction? One possibility is that breeders extend their lifespans by outsourcing parental care to non-reproductive group members. Having help lightens breeder workloads and the energy that is saved can be allocated to survival instead. We tested this hypothesis using phylogenetic meta-analysis across 23 cooperatively breeding bird species. We found that breeders with helpers had higher rates of annual survival than those without helpers (8% on average). Increased breeder survival was correlated with reduced investment in feeding offspring, which in turn depended on the proportion of feeding provided by helpers. Helpers had similar effects on female and male breeder survival. Our results indicate that one of the secrets to a long life is reduced investment in parental care. This appears to be a unique feature of cooperative societies with hard-working helpers. This article is part of the theme issue 'Ageing and sociality: why, when and how does sociality change ageing patterns?'
Asunto(s)
Aves/fisiología , Conducta Cooperativa , Rasgos de la Historia de Vida , Longevidad , Comportamiento de Nidificación , Conducta Social , Animales , Femenino , Masculino , Filogenia , Pájaros Cantores/fisiologíaRESUMEN
Since Hamilton published his seminal papers in 1964, our understanding of the importance of cooperation for life on Earth has evolved beyond recognition. Early research was focused on altruism in the social insects, where the problem of cooperation was easy to see. In more recent years, research into cooperation has expanded across the entire tree of life, and has been revolutionized by advances in genetic, microbiological and analytical techniques. We highlight ten insights that have arisen from these advances, which have illuminated generalizations across different taxa, making the world simpler to explain. Furthermore, progress in these areas has opened up numerous new problems to solve, suggesting exciting directions for future research.
Asunto(s)
Evolución Biológica , Conducta Cooperativa , Altruismo , Animales , InsectosRESUMEN
Male-only parental care, while rare in most animals, is a widespread strategy within teleost fish. The costs and benefits to males of acting as sole carer are highly variable among fish species making it challenging to determine the selective pressures driving the evolution of male-only care to such a high prevalence. We conducted a phylogenetic meta-analysis to examine the costs and benefits of paternal care across fish species. We found no evidence that providing care negatively affects male condition. In contrast with other taxa, we also found limited evidence that male care has evolved as a strategy to improve offspring survival. Instead, we found that males already caring for a brood are preferred by females and that this preference is strongest in those species in which males work harder to care for larger broods. Thus, in fish, investment in offspring care does not constrain a male's mating success but rather augments it, suggesting that the relatively high prevalence of male-only care in fish may be in part explained by sexual selection through female preference for caring males.
Asunto(s)
Peces , Conducta Paterna , Conducta Sexual Animal , Animales , Análisis Costo-Beneficio , Padre , Femenino , Masculino , Filogenia , ReproducciónRESUMEN
In birds that breed cooperatively in family groups, adult offspring often delay dispersal to assist the breeding pair in raising their young. Kin selection is thought to play an important role in the evolution of this breeding system. However, evidence supporting the underlying assumption that helpers increase the reproductive success of breeders is inconsistent. In 10 out of 19 species where the effect of helpers on breeder reproductive success has been estimated while controlling for the effects of breeder and territory quality, no benefits of help were detected. Here, we use phylogenetic meta-analysis to show that the inconsistent evidence for helper benefits across species is explained by study design. After accounting for low sample sizes and the different study designs used to control for breeder and territory quality, we found that helpers consistently enhanced the reproductive success of breeders. Therefore, the assumption that helpers increase breeder reproductive success is supported by evidence across cooperatively breeding birds.
Asunto(s)
Conducta Cooperativa , Passeriformes/fisiología , Reproducción/fisiología , Animales , Conducta Animal , Comportamiento de Nidificación/fisiologíaRESUMEN
Group-living species show a diversity of social organization, from simple mated pairs to complex communities of interdependent individuals performing specialized tasks. The advantages of living in cooperative groups are well understood, but why some species breed in small aggregations while others evolve large, complex groups with clearly divided roles is unclear. We address this problem by reconstructing the evolutionary pathways to cooperative breeding across 4,730 bird species. We show that differences in the way groups form at the origin of cooperative breeding predicts the level of group complexity that emerges. Groups that originate through the retention of offspring have a clear reproductive divide with distinct breeder and helper roles. This is associated with reproductive specialization, where breeders invest more in fecundity and less in care. In contrast, groups formed through the aggregation of unrelated adults are smaller and lack specialization. These results help explain why some species have not transitioned beyond simple groups while others have taken the pathway to increased group complexity.
Asunto(s)
Evolución Biológica , Aves , Animales , Cruzamiento , ReproducciónRESUMEN
Inclusive fitness requires a careful accounting of all the fitness effects of a particular behavior. Verbal arguments can potentially exaggerate the inclusive fitness consequences of a behavior by including the fitness of relatives that was not caused by that behavior, leading to error. We show how this "double-counting" error can arise, with a recent example from the signaling literature. In particular, we examine the recent debate over whether parental divorce increases parent-offspring conflict, selecting for less honest signaling. We found that, when all the inclusive fitness consequences are accounted for, parental divorce increases conflict between siblings, in a way that they can select for less honest signaling. This prediction is consistent with the empirical data. More generally, our results illustrate how verbal arguments can be misleading, emphasizing the advantage of formal mathematical models.
RESUMEN
The growth and virulence of bacteria depends upon a number of factors that are secreted into the environment. These factors can diffuse away from the producing cells, to be either lost or used by cells that do not produce them (cheats). Mechanisms that act to reduce the loss of secreted factors through diffusion are expected to be favoured. One such mechanism may be the production of Fap fibrils, needle-like fibres on the cell surface observed in P. aeruginosa, which can transiently bind several secreted metabolites produced by cells. We test whether Fap fibrils help retain a secreted factor, the iron-scavenging molecule pyoverdine, and hence reduce the potential for exploitation by non-producing, cheating cells. We found that: (i) wild-type cells retain more iron-chelating metabolites than fibril non-producers; (ii) purified Fap fibrils can prevent the loss of the iron-chelators PQS ( Pseudomonas quinolone signal) and pyoverdine; and (iii) pyoverdine non-producers have higher fitness in competition with fibril non-producers than with wild-type cells. Our results suggest that by limiting the loss of a costly public good, Fap fibrils may play an important role in stabilizing cooperative production of secreted factors.
Asunto(s)
Amiloide/metabolismo , Proteínas Bacterianas/metabolismo , Hierro/metabolismo , Oligopéptidos/metabolismo , Pseudomonas aeruginosa/fisiología , Sideróforos/metabolismoRESUMEN
A single cheating mutant can lead to the invasion and eventual eradication of cooperation from a population. Consequently, cheat invasion is often considered equal to extinction in empirical and theoretical studies of cooperator-cheat dynamics. But does cheat invasion necessarily equate extinction in nature? By following the social dynamics of iron metabolism in Pseudomonas aeruginosa during cystic fibrosis lung infection, we observed that individuals evolved to replace cooperation with a 'private' behaviour. Phenotypic assays showed that cooperative iron acquisition frequently was upregulated early in infection, which, however, increased the risk of cheat invasion. With whole-genome sequencing we showed that if, and only if, cooperative iron acquisition is lost from the population, a private system was upregulated. The benefit of upregulation depended on iron availability. These findings highlight the importance of social dynamics of natural populations and emphasizes the potential impact of past social interaction on the evolution of private traits.
Asunto(s)
Regulación Bacteriana de la Expresión Génica , Hierro/metabolismo , Infecciones por Pseudomonas/microbiología , Pseudomonas aeruginosa/metabolismo , Fibrosis Quística/complicaciones , Genética de Población , Pseudomonas aeruginosa/genética , Secuenciación Completa del GenomaRESUMEN
The evolution of helping behaviour in species that breed cooperatively in family groups is typically attributed to kin selection alone. However, in many species, helpers go on to inherit breeding positions in their natal groups, but the extent to which this contributes to selection for helping is unclear as the future reproductive success of helpers is often unknown. To quantify the role of future reproduction in the evolution of helping, we compared the helping effort of female and male retained offspring across cooperative birds. The kin selected benefits of helping are equivalent between female and male helpers-they are equally related to the younger siblings they help raise-but the future reproductive benefits of helping differ because of sex differences in the likelihood of breeding in the natal group. We found that the sex which is more likely to breed in its natal group invests more in helping, suggesting that in addition to kin selection, helping in family groups is shaped by future reproduction.
Asunto(s)
Aves/fisiología , Comportamiento de Nidificación , Reproducción , Animales , Conducta Cooperativa , Femenino , Conducta de Ayuda , Masculino , Caracteres SexualesRESUMEN
Bacteria perform cooperative behaviors that are exploitable by noncooperative cheats, and cheats frequently arise and coexist with cooperators in laboratory microcosms. However, evidence of competitive dynamics between cooperators and cheats in nature remains limited. Using the production of pyoverdine, an iron-scavenging molecule, and natural soil populations of Pseudomonas fluorescens, we found that (1) nonproducers are present in the population; (2) they co-occur (<1cm3 ) with pyoverdine producers; (3) they retain functional pyoverdine receptors; and (4) they can use the pyoverdine of on average 52% of producers. This suggests nonproducers can potentially act as social cheats in soil: utilizing the pyoverdine of others while producing little or none themselves. However, we found considerable variation in the extent to which nonproducers can exploit producers, as some isolates appear to produce exclusive forms of pyoverdine or kill nonproducers with toxins. We examined the consequences of this variation using theoretical modeling. We found variance in exploitability leads to some cheats gaining increased fitness benefits and others decreased benefits. However, the absolute gain in fitness from high exploitation is lower than the drop in fitness from low exploitation, decreasing the mean fitness of cheats and subsequently lowering the proportion of cheats maintained in the population. Our results suggest that although cooperator-cheat dynamics can occur in soil, a range of mechanisms can prevent nonproducers from exploiting producers.
Asunto(s)
Interacciones Microbianas/genética , Pseudomonas/genética , Microbiología del Suelo , Aptitud Genética , Variación Genética , Oligopéptidos/genética , Oligopéptidos/metabolismo , Pseudomonas/metabolismo , Pseudomonas/fisiologíaRESUMEN
Animals living in harsh environments, where temperatures are hot and rainfall is unpredictable, are more likely to breed in cooperative groups. As a result, harsh environmental conditions have been accepted as a key factor explaining the evolution of cooperation. However, this is based on evidence that has not investigated the order of evolutionary events, so the inferred causality could be incorrect. We resolved this problem using phylogenetic analyses of 4,707 bird species and found that causation was in the opposite direction to that previously assumed. Rather than harsh environments favouring cooperation, cooperative breeding has facilitated the colonization of harsh environments. Cooperative breeding was, in fact, more likely to evolve from ancestors occupying relatively cool environmental niches with predictable rainfall, which had low levels of polyandry and hence high within-group relatedness. We also found that polyandry increased after cooperative breeders invaded harsh environments, suggesting that when helpers have limited options to breed independently, polyandry no longer destabilizes cooperation. This provides an explanation for the puzzling cases of polyandrous cooperative breeding birds. More generally, this illustrates how cooperation can play a key role in invading ecological niches, a pattern observed across all levels of biological organization from cells to animal societies.