Francisco Dionisio | Universidade de Lisboa (original) (raw)

Papers by Francisco Dionisio

Genetics, 2002

Conjugative plasmids can mediate gene transfer between bacterial taxa in diverse environments. Th... more Conjugative plasmids can mediate gene transfer between bacterial taxa in diverse environments. The ability to donate the F-type conjugative plasmid R1 greatly varies among enteric bacteria due to the interaction of the system that represses sex-pili formations (products of finOP) of plasmids already harbored by a bacterial strain with those of the R1 plasmid. The presence of efficient donors in heterogeneous bacterial populations can accelerate plasmid transfer and can spread by several orders of magnitude. Such donors allow millions of other bacteria to acquire the plasmid in a matter of days whereas, in the absence of such strains, plasmid dissemination would take years. This "amplification effect" could have an impact on the evolution of bacterial pathogens that exist in heterogeneous bacterial communities because conjugative plasmids can carry virulence or antibiotic-resistance genes.

Evolutionary Ecology Research, 2007

Background: A tragedy of the commons arises if individuals cannot protect their future use of a d... more Background: A tragedy of the commons arises if individuals cannot protect their future use of a depletable resource, and individual fitness increases if individuals exploit the resource at rates beyond sustainability. Natural selection then forces the individuals to diminish, perhaps even to destroy, their resource. One way to protect future use is privatization – that is, locally excluding rivals from the resource. Another is to reduce rivalry among individuals by restricting exploitation rates. Questions: Under what conditions will natural selection increase excludability? If relatedness among individuals is high, will kin selection be enough to eliminate or weaken the evolution of privatization? Mathematical method: We use a simple model that captures the tension between individual and group success. Then, we calculate the evolutionarily stable strategy using the standard optimization techniques of evolutionary game theory. Conclusions: Selection for privatization occurs at low v...

Antibiotics, 2021

Human metagenomes with a high diversity of virulence genes tend to have a high diversity of antib... more Human metagenomes with a high diversity of virulence genes tend to have a high diversity of antibiotic-resistance genes and vice-versa. To understand this positive correlation, we simulated the transfer of these genes and bacterial pathogens in a community of interacting people that take antibiotics when infected by pathogens. Simulations show that people with higher diversity of virulence and resistance genes took antibiotics long ago, not recently. On the other extreme, we find people with low diversity of both gene types because they took antibiotics recently—while antibiotics select specific resistance genes, they also decrease gene diversity by eliminating bacteria. In general, the diversity of virulence and resistance genes becomes positively correlated whenever the transmission probability between people is higher than the probability of losing resistance genes. The positive correlation holds even under changes of several variables, such as the relative or total diversity of ...

The perfect condition for the rising of superbugs: person-to-person contagion and 1 antibiotic us... more The perfect condition for the rising of superbugs: person-to-person contagion and 1 antibiotic use are the key factors responsible for the positive correlation between 2 antibiotic resistance gene diversity and virulence gene diversity in human 3 metagenomes 4 5 Célia P. F. Domingues, João S. Rebelo, Teresa Nogueira , Joël Pothier, 6 Francisca Monteiro, and Francisco Dionisio* 7 1 cE3c – Centre for Ecology, Evolution and Environmental Changes, Faculdade de 8 Ciências, Universidade de Lisboa, 1749-016 Lisboa, Portugal 9 2 INIAV National Institute for Agrarian and Veterinary Research, Bacteriology and 10 Mycology Laboratory, 2780 -157 Oeiras, Portugal 11 3 Atelier de Bioinformatique, ISYEB, UMR 7205 CNRS MNHN UPMC EPHE, 12 Muséum National d’Histoire Naturelle, CP 50, 45 rue Buffon F-75005 Paris, France 13 † These authors have contributed equally to this work 14 *Correspondence: 15 Francisco Dionisio 16 dionisio@fc.ul.pt 17

Evolutionary Ecology Research, 2005

Problem: Conjugative plasmids manipulate their bacterial hosts to express sex-pili – long, filame... more Problem: Conjugative plasmids manipulate their bacterial hosts to express sex-pili – long, filamentous organelles whose genes are carried by the plasmids themselves. Sex-pili locate and attach to another bacterial cell for plasmid transfer. Bacteria differ in their ability to express sex-pili and hence to donate plasmids. Does this diversity in sex-pilus expression contribute to the survival of conjugative plasmids? Method: Simulations of a chemostat containing bacterial cells, some harbouring a conjugative plasmid. Certain viruses, called male-specific phages (MSPs), enter the chemostat. These viruses infect only donor cells. I monitor whether plasmids continue to survive in each simulation. Key assumption: A bacterium’s ability to donate is proportional to its susceptibility to MSPs. Conclusions: Bacterial diversity in sex-pilus expression strongly increases the size of the parameter space for plasmid survival. A host with low expression of sex-pili – and hence a low plasmid trans...

Problem: In the study of conflicts, both economists and evolutionary biologists use the concepts ... more Problem: In the study of conflicts, both economists and evolutionary biologists use the concepts ‘tragedy of the commons’ and ‘public goods dilemma’. What is the relationship between the economist and evolutionist views of these concepts? Model features: The economics literature defines the tragedy of the commons and the public goods dilemma in terms of rivalry and excludability of the good. In contrast, evolutionists define these conflicts based on fitness functions with two components: individual and group components of fitness. Mathematical method: Evolutionary game theory and the calculation of evolutionarily stable strategy trait values by standard optimization techniques and by replacing slopes of group phenotype on individual genotype by coefficients of relatedness. Conclusion: There is a direct relationship between rivalry and the individual component of fitness and between excludability and the group component of fitness. Moreover, although the prisoner’s dilemma constitute...

Evolutionary Ecology Research, 2007

Questions: Can hosts use their parasites or pathogens to decrease the fitness of their conspecifi... more Questions: Can hosts use their parasites or pathogens to decrease the fitness of their conspecifics? Which conditions support the evolution of such harmful behaviour – expressed as spiteful or selfish behaviour? Mathematical model: I calculate the selective pressure acting on a mutant expressing harmful behaviour. The direction of selection on this social trait is given by its effect on inclusive fitness. Individuals are haploid and form a population of constant size and structured in an infinite island model with migration. Individuals harm others through their parasites or pathogens. Key assumptions: (1) An infected host may infect several other susceptible conspecifics simultaneously. (2) A variety of immunity mechanisms enables kin members to be immune to a given parasite or pathogen, a sort of kin recognition. Conclusions: By using parasites to harm non-kin hosts, the harming host may partially align its interests with those of the parasites, even when there is a fitness cost f...

PLOS ONE

Antibiotic-susceptible bacteria may survive bactericidal antibiotics if other co-inhabiting bacte... more Antibiotic-susceptible bacteria may survive bactericidal antibiotics if other co-inhabiting bacteria detoxify the medium through antibiotic degradation or modification, a phenomenon denominated as indirect resistance. However, it is unclear how susceptible cells survive while the medium is still toxic. One explanation relies on the speed of detoxification, and another, non-exclusive explanation, relies on persistence, a state of bacterial dormancy where cells with low metabolic activity and growth rates are phenotypically tolerant to antibiotics and other cytotoxic substances. Here we simulated the fate of susceptible cells in laboratory experiments in the context of indirect resistance to understand whether persistence is necessary to explain the survival of susceptible cells. Depending on the strain and experimental conditions, the decay of persister populations may follow an exponential or a power-law distribution. Therefore, we studied the impact of both distributions in the sim...

Frontiers in Microbiology

It is difficult to understand plasmid maintenance in the absence of selection and theoretical mod... more It is difficult to understand plasmid maintenance in the absence of selection and theoretical models predict the conditions for plasmid persistence to be limited. Plasmid-associated fitness costs decrease bacterial competitivity, while imperfect partition allows the emergence of plasmid-free cells during cell division. Although plasmid conjugative transfer allows mobility into plasmid-free cells, the rate of such events is generally not high enough to ensure plasmid persistence. Experimental data suggest several factors that may expand the conditions favorable for plasmid maintenance, such as compensatory mutations and accessory genes that allow positive selection. Most of the previous studies focus on bacteria that carry a single plasmid. However, there is increasing evidence that multiple plasmids inhabit the same bacterial population and that interactions between them affect their transmission and persistence. Here, we adapt previous mathematical models to include multiple plasmids and perform computer simulations to study how interactions among them affect plasmid maintenance. We tested the contribution of different plasmid interaction parameters that impact three biological features: host fitness, conjugative transfer and plasmid loss – which affect plasmid persistence. The interaction affecting conjugation was studied in the contexts of intracellular and intercellular interactions, i.e., the plasmids interact when present in the same cell or when in different cells, respectively. First, we tested the effect of each type of interaction alone and concluded that only interactions affecting fitness (epistasis) prevented plasmid extinction. Although not allowing plasmid maintenance, intracellular interactions increasing conjugative efficiencies had a more determinant impact in delaying extinction than the remaining parameters. Then, we allowed multiple interactions between plasmids and concluded that, in a few cases, a combined effect of (intracellular) interactions increasing conjugation and fitness lead to plasmid maintenance. Our results show a hierarchy among these interaction parameters. Those affecting fitness favor plasmid persistence more than those affecting conjugative transfer and lastly plasmid loss. These results suggest that interactions between different plasmids can favor their persistence in bacterial communities.

Persistence is a state of bacterial dormancy where cells with low metabolic activity and growth r... more Persistence is a state of bacterial dormancy where cells with low metabolic activity and growth rates are phenotypically tolerant to antibiotics and other cytotoxic substances. Given its obvious advantage to bacteria, several researchers have been looking for the genetic mechanism behind persistence. However, other authors argue that there is no such mechanism and that persistence results from inadvertent cell errors. In this case, the persistent population should decay according to a power-law with a particular exponent of −2. Studying persisters’ decay is, therefore, a valuable way to understand persistence. Here we simulated the fate of susceptible cells in laboratory experiments in the context of indirect resistance. Eventually, under indirect resistance, detoxifying drug-resistant cells save the persister cells that leave the dormant state and resume growth. The simulations presented here show that, by assuming a power-law decline, the exponent is close to −2, which is the expe...

Journal of Health Psychology

Attachment security has been associated with health status and symptom reporting. In this longitu... more Attachment security has been associated with health status and symptom reporting. In this longitudinal study, we investigated the association between antibiotics uptake by infants at 9-months and mother-infant attachment at 12-months. Logistic regression analyses indicated that lower maternal sensitivity was associated with increased odds of antibiotic uptake. Furthermore, 89.7% of insecure-ambivalent infants consumed antibiotics, which contrasted with 32.5% of avoidant infants and 21.5% of secure infants. This study suggests that maternal behavior and mother-infant attachment impact on antibiotic consumption, which is worrying because antibiotics may lead to several health problems later in life and antibiotic-resistance.

Frontiers in Microbiology

Bacterial biofilms have an impact in medical and industrial environments because they often confe... more Bacterial biofilms have an impact in medical and industrial environments because they often confer protection to bacteria against harmful agents, and constitute a source from which microorganisms can disperse. Conjugative plasmids can enhance bacterial ability to form biofilms because conjugative pili act as adhesion factors. However, plasmids may interact with each other, either facilitating or inhibiting plasmid transfer. Accordingly, we asked whether effects on plasmid transfer also impacts biofilm formation. We measured biofilm formation of Escherichia coli cells harboring two plasmid types, or when the two plasmids were present in the same population but carried in different cells. Using eleven natural isolated conjugative plasmids, we confirmed that some indeed promote biofilm formation and, importantly, that this ability is correlated with conjugative efficiency. Further we studied the effect of plasmid pairs on biofilm formation. We observed increased biofilm formation in approximately half of the combinations when both plasmids inhabited the same cell or when the plasmids were carried in different cells. Moreover, in approximately half of the combinations, independent of the co-inhabitation conditions, one of the plasmids alone determined the extent of biofilm formation-thus having a dominant effect over the other plasmid. The molecular mechanisms responsible for these interactions were not evaluated here and future research is required to elucidate them.

Antibiotics have been used on a large scale in veterinary and medical contexts. The massive and c... more Antibiotics have been used on a large scale in veterinary and medical contexts. The massive and continuous exposure to antimicrobial drugs has led to the emergence and spread of antibiotic resistance, which is nowadays one of the greatest threats to public health. Although antibiotics are used to treat bacterial infections, it is not only pathogenic bacteria that are affected. Upon exposure to antimicrobial drugs, bacteria that are resistant to the antibiotic administered are selected. Therefore, resistance and pathogenicity may be associated. It was recently shown that there is a positive correlation between the diversity of antibiotic resistance genes and the diversity of pathogenicity genes in human metagenomes from different geographical origins. Our study aimed to understand the factors that lead to the establishment of this positive correlation in human populations using computer simulations. Our results suggest that this positive correlation emerges if the contagion probabili...

mSphere

Human beings have used large amounts of antibiotics, not only in medical contexts but also, for e... more Human beings have used large amounts of antibiotics, not only in medical contexts but also, for example, as growth factors in agriculture and livestock, resulting in the contamination of the environment. Even when pathogenic bacteria are the targets of antibiotics, hundreds of nonpathogenic bacterial species are affected as well. Therefore, both pathogenic and nonpathogenic bacteria have gradually become resistant to antibiotics. We tested whether there is still cooccurrence of resistance and virulence determinants. We performed a comparative study of environmental and human gut metagenomes from different individuals and from distinct human populations across the world. We found a great diversity of antibiotic resistance determinants (AR diversity [ARd]) and virulence factors (VF diversity [VFd]) in metagenomes. Importantly there is a correlation between ARd and VFd, even after correcting for protein family richness. In the human gut, there are less ARd and VFd than in more diversif...

Plasmid

Plasmids are genetic elements that play a role in bacterial evolution by providing new genes that... more Plasmids are genetic elements that play a role in bacterial evolution by providing new genes that promote adaptation to diverse conditions. Plasmids are also known to reduce bacterial competitiveness in the absence of selection for plasmid-encoded traits. It is easier to understand plasmid persistence when considering the evidence that plasmid maintenance can improve during co-evolution with the bacterial host, i.e. the chromosome. However, bacteria isolated from nature often harbor diverse mobile elements: phages, transposons, genomic islands and even other plasmids. Recent interest has emerged on the role such elements play on the persistence and evolution of plasmids. Here, we mainly review interactions between different plasmids, but also discuss their interactions with other genetic elements. We focus on interactions that impact fundamental plasmid traits, such as the fitness effect imposed on their hosts and the transfer efficiency into new host cells. We illustrate these phenomena with examples concerning clinically relevant organisms and the spread of plasmids carrying antibiotic resistance genes and virulence factors.

Human beings have used large amounts of antibiotics, not only in medical contexts but also, for e... more Human beings have used large amounts of antibiotics, not only in medical contexts but also, for example, as growth factors in agriculture and livestock, resulting in the contamination of the environment. Even when pathogenic bacteria are the targets of antibiotics, hundreds of non-pathogenic bacterial species are affected as well. Therefore, both pathogenic and non-pathogenic bacteria have gradually become resistant to antibiotics. We tested whether there is still co-occurrence of resistance and virulence determinants. We performed a comparative study of environmental and human gut metagenomes issuing from different individuals and from distinct human populations across the world. We found a great diversity of antibiotic resistance determinants (ARd) and virulence factors (VFd) in metagenomes. Importantly there is a correlation between ARd and VFd, even after correcting for protein family richness. In the human gut there are less ARd and VFd than in more diversified environments, an...

Plasmid

Naturally occurring plasmids have medical importance given that they frequently code for virulenc... more Naturally occurring plasmids have medical importance given that they frequently code for virulence or antibiotic resistance. In many cases, plasmids impose a fitness cost to their hosts, meaning that the growth rate of plasmid-bearing cells is lower than that of plasmid-free cells. However, this does not fit with the fact that plasmids are ubiquitous in nature nor that plasmids and their hosts adapt to each other very fast - as has been shown in laboratory evolutionary assays. Even when plasmids are costly, they seem to largely interact in such a way that the cost of two plasmids is lower than the cost of one of them alone. Moreover, it has been argued that transfer rates are too low to compensate for plasmid costs and segregation. Several mechanisms involving interactions between plasmids and other replicons could overcome this limitation, hence contributing to the maintenance of plasmids in bacterial populations. We examine the importance of these mechanisms from a clinical point of view, particularly the spread of antibiotic resistance genes.

Bulletin of Mathematical Biology

Humans are often colonized by polymorphic bacteria such as Streptococcus pneumoniae, Bordetella p... more Humans are often colonized by polymorphic bacteria such as Streptococcus pneumoniae, Bordetella pertussis, Staphylococcus Aureus, and Haemophilus influenzae. Two co-colonizing pathogen clones may interact with each other upon host entry and during within-host dynamics, ranging from competition to facilitation. Here we examine the significance of these exploitation strategies for bacterial spread and persistence in host populations. We model SIS epidemiological dynamics to capture the global behavior of such multi-strain systems, focusing on different parameters of single and dual colonization. We analyze the impact of heterogeneity in clearance and transmission rates of single and dual colonization and find the criteria under which these asymmetries enhance endemic persistence. We obtain a backward bifurcation near R_0 = 1$$R0=1 if the reproductive value of the parasite in dually infected hosts is sufficiently higher than that in singly infected ones. In such cases, the parasite is able to persist even in sub-threshold conditions, and reducing the basic reproduction number below 1 would be insufficient for elimination. The fitness superiority in co-colonized hosts can be attained by lowering net parasite clearance rate ($$\gamma _\mathrm{{d}}$$γd), by increasing transmission rate ($$\beta _\mathrm{{d}}$$βd), or both, and coupling between these traits critically constrains opportunities of pathogen survival in the R_0<1$$R0<1 regime. Finally, using an adaptive dynamics approach, we verify that despite their importance for sub-threshold endemicity, traits expressed exclusively in coinfection should generally evolve independently of single infection traits. In particular, for \beta _\mathrm{{d}}$$βd a saturating parabolic or hyperbolic function of \gamma _\mathrm{{d}}$$γd, co-colonization traits evolve to an intermediate optimum (evolutionarily stable strategy, ESS), determined only by host lifespan and the trade-off parameters linking \beta _\mathrm{{d}}$$βd and \gamma _\mathrm{{d}}$$γd. Our study invites more empirical attention to the dynamics and evolution of parasite life-history traits expressed exclusively in coinfection.

Plasmid

Conjugative plasmids encode genes that enable them to transfer, by conjugation, from a given host... more Conjugative plasmids encode genes that enable them to transfer, by conjugation, from a given host cell to another cell. Conjugative transfer, despite being an important feature of conjugative plasmids, is not constitutive for most plasmids, the reason being that genes involved in horizontal transfer are mostly repressed. Only upon their transient de-repression are plasmids able to transfer horizontally. If host cells harbour multiple plasmids, their simultaneous transfer depends on simultaneous transient de-repression of all plasmids. If de-repression of different plasmids was random and independent events, simultaneous de-repression should be a rare event because the probability of simultaneous de-repression would be the product of the probabilities of de-repression of each plasmid. Some previous observations support this hypothesis, while others show that co-transfer of plasmids is more frequent than this reasoning indicates. Here, we show that co-transfer of multiple plasmids mainly results from non-independent events: the probability that all plasmids within a cell become de-repressed is much higher than if de-repression of plasmids genes were independent. We found a simple model for the probability of co-transfer: the plasmid having the lowest conjugation rates is the one who limits co-transfer. In this sense, cells receiving the plasmid with the lower transfer rate also receive the other plasmid. If de-repression happens simultaneously on co-resident plasmids, common cues may stimulate de-repression of distinct plasmids.

Genetics, 2002

Conjugative plasmids can mediate gene transfer between bacterial taxa in diverse environments. Th... more Conjugative plasmids can mediate gene transfer between bacterial taxa in diverse environments. The ability to donate the F-type conjugative plasmid R1 greatly varies among enteric bacteria due to the interaction of the system that represses sex-pili formations (products of finOP) of plasmids already harbored by a bacterial strain with those of the R1 plasmid. The presence of efficient donors in heterogeneous bacterial populations can accelerate plasmid transfer and can spread by several orders of magnitude. Such donors allow millions of other bacteria to acquire the plasmid in a matter of days whereas, in the absence of such strains, plasmid dissemination would take years. This "amplification effect" could have an impact on the evolution of bacterial pathogens that exist in heterogeneous bacterial communities because conjugative plasmids can carry virulence or antibiotic-resistance genes.

Evolutionary Ecology Research, 2007

Background: A tragedy of the commons arises if individuals cannot protect their future use of a d... more Background: A tragedy of the commons arises if individuals cannot protect their future use of a depletable resource, and individual fitness increases if individuals exploit the resource at rates beyond sustainability. Natural selection then forces the individuals to diminish, perhaps even to destroy, their resource. One way to protect future use is privatization – that is, locally excluding rivals from the resource. Another is to reduce rivalry among individuals by restricting exploitation rates. Questions: Under what conditions will natural selection increase excludability? If relatedness among individuals is high, will kin selection be enough to eliminate or weaken the evolution of privatization? Mathematical method: We use a simple model that captures the tension between individual and group success. Then, we calculate the evolutionarily stable strategy using the standard optimization techniques of evolutionary game theory. Conclusions: Selection for privatization occurs at low v...

Antibiotics, 2021

Human metagenomes with a high diversity of virulence genes tend to have a high diversity of antib... more Human metagenomes with a high diversity of virulence genes tend to have a high diversity of antibiotic-resistance genes and vice-versa. To understand this positive correlation, we simulated the transfer of these genes and bacterial pathogens in a community of interacting people that take antibiotics when infected by pathogens. Simulations show that people with higher diversity of virulence and resistance genes took antibiotics long ago, not recently. On the other extreme, we find people with low diversity of both gene types because they took antibiotics recently—while antibiotics select specific resistance genes, they also decrease gene diversity by eliminating bacteria. In general, the diversity of virulence and resistance genes becomes positively correlated whenever the transmission probability between people is higher than the probability of losing resistance genes. The positive correlation holds even under changes of several variables, such as the relative or total diversity of ...

The perfect condition for the rising of superbugs: person-to-person contagion and 1 antibiotic us... more The perfect condition for the rising of superbugs: person-to-person contagion and 1 antibiotic use are the key factors responsible for the positive correlation between 2 antibiotic resistance gene diversity and virulence gene diversity in human 3 metagenomes 4 5 Célia P. F. Domingues, João S. Rebelo, Teresa Nogueira , Joël Pothier, 6 Francisca Monteiro, and Francisco Dionisio* 7 1 cE3c – Centre for Ecology, Evolution and Environmental Changes, Faculdade de 8 Ciências, Universidade de Lisboa, 1749-016 Lisboa, Portugal 9 2 INIAV National Institute for Agrarian and Veterinary Research, Bacteriology and 10 Mycology Laboratory, 2780 -157 Oeiras, Portugal 11 3 Atelier de Bioinformatique, ISYEB, UMR 7205 CNRS MNHN UPMC EPHE, 12 Muséum National d’Histoire Naturelle, CP 50, 45 rue Buffon F-75005 Paris, France 13 † These authors have contributed equally to this work 14 *Correspondence: 15 Francisco Dionisio 16 dionisio@fc.ul.pt 17

Evolutionary Ecology Research, 2005

Problem: Conjugative plasmids manipulate their bacterial hosts to express sex-pili – long, filame... more Problem: Conjugative plasmids manipulate their bacterial hosts to express sex-pili – long, filamentous organelles whose genes are carried by the plasmids themselves. Sex-pili locate and attach to another bacterial cell for plasmid transfer. Bacteria differ in their ability to express sex-pili and hence to donate plasmids. Does this diversity in sex-pilus expression contribute to the survival of conjugative plasmids? Method: Simulations of a chemostat containing bacterial cells, some harbouring a conjugative plasmid. Certain viruses, called male-specific phages (MSPs), enter the chemostat. These viruses infect only donor cells. I monitor whether plasmids continue to survive in each simulation. Key assumption: A bacterium’s ability to donate is proportional to its susceptibility to MSPs. Conclusions: Bacterial diversity in sex-pilus expression strongly increases the size of the parameter space for plasmid survival. A host with low expression of sex-pili – and hence a low plasmid trans...

Problem: In the study of conflicts, both economists and evolutionary biologists use the concepts ... more Problem: In the study of conflicts, both economists and evolutionary biologists use the concepts ‘tragedy of the commons’ and ‘public goods dilemma’. What is the relationship between the economist and evolutionist views of these concepts? Model features: The economics literature defines the tragedy of the commons and the public goods dilemma in terms of rivalry and excludability of the good. In contrast, evolutionists define these conflicts based on fitness functions with two components: individual and group components of fitness. Mathematical method: Evolutionary game theory and the calculation of evolutionarily stable strategy trait values by standard optimization techniques and by replacing slopes of group phenotype on individual genotype by coefficients of relatedness. Conclusion: There is a direct relationship between rivalry and the individual component of fitness and between excludability and the group component of fitness. Moreover, although the prisoner’s dilemma constitute...

Evolutionary Ecology Research, 2007

Questions: Can hosts use their parasites or pathogens to decrease the fitness of their conspecifi... more Questions: Can hosts use their parasites or pathogens to decrease the fitness of their conspecifics? Which conditions support the evolution of such harmful behaviour – expressed as spiteful or selfish behaviour? Mathematical model: I calculate the selective pressure acting on a mutant expressing harmful behaviour. The direction of selection on this social trait is given by its effect on inclusive fitness. Individuals are haploid and form a population of constant size and structured in an infinite island model with migration. Individuals harm others through their parasites or pathogens. Key assumptions: (1) An infected host may infect several other susceptible conspecifics simultaneously. (2) A variety of immunity mechanisms enables kin members to be immune to a given parasite or pathogen, a sort of kin recognition. Conclusions: By using parasites to harm non-kin hosts, the harming host may partially align its interests with those of the parasites, even when there is a fitness cost f...

PLOS ONE

Antibiotic-susceptible bacteria may survive bactericidal antibiotics if other co-inhabiting bacte... more Antibiotic-susceptible bacteria may survive bactericidal antibiotics if other co-inhabiting bacteria detoxify the medium through antibiotic degradation or modification, a phenomenon denominated as indirect resistance. However, it is unclear how susceptible cells survive while the medium is still toxic. One explanation relies on the speed of detoxification, and another, non-exclusive explanation, relies on persistence, a state of bacterial dormancy where cells with low metabolic activity and growth rates are phenotypically tolerant to antibiotics and other cytotoxic substances. Here we simulated the fate of susceptible cells in laboratory experiments in the context of indirect resistance to understand whether persistence is necessary to explain the survival of susceptible cells. Depending on the strain and experimental conditions, the decay of persister populations may follow an exponential or a power-law distribution. Therefore, we studied the impact of both distributions in the sim...

Frontiers in Microbiology

It is difficult to understand plasmid maintenance in the absence of selection and theoretical mod... more It is difficult to understand plasmid maintenance in the absence of selection and theoretical models predict the conditions for plasmid persistence to be limited. Plasmid-associated fitness costs decrease bacterial competitivity, while imperfect partition allows the emergence of plasmid-free cells during cell division. Although plasmid conjugative transfer allows mobility into plasmid-free cells, the rate of such events is generally not high enough to ensure plasmid persistence. Experimental data suggest several factors that may expand the conditions favorable for plasmid maintenance, such as compensatory mutations and accessory genes that allow positive selection. Most of the previous studies focus on bacteria that carry a single plasmid. However, there is increasing evidence that multiple plasmids inhabit the same bacterial population and that interactions between them affect their transmission and persistence. Here, we adapt previous mathematical models to include multiple plasmids and perform computer simulations to study how interactions among them affect plasmid maintenance. We tested the contribution of different plasmid interaction parameters that impact three biological features: host fitness, conjugative transfer and plasmid loss – which affect plasmid persistence. The interaction affecting conjugation was studied in the contexts of intracellular and intercellular interactions, i.e., the plasmids interact when present in the same cell or when in different cells, respectively. First, we tested the effect of each type of interaction alone and concluded that only interactions affecting fitness (epistasis) prevented plasmid extinction. Although not allowing plasmid maintenance, intracellular interactions increasing conjugative efficiencies had a more determinant impact in delaying extinction than the remaining parameters. Then, we allowed multiple interactions between plasmids and concluded that, in a few cases, a combined effect of (intracellular) interactions increasing conjugation and fitness lead to plasmid maintenance. Our results show a hierarchy among these interaction parameters. Those affecting fitness favor plasmid persistence more than those affecting conjugative transfer and lastly plasmid loss. These results suggest that interactions between different plasmids can favor their persistence in bacterial communities.

Persistence is a state of bacterial dormancy where cells with low metabolic activity and growth r... more Persistence is a state of bacterial dormancy where cells with low metabolic activity and growth rates are phenotypically tolerant to antibiotics and other cytotoxic substances. Given its obvious advantage to bacteria, several researchers have been looking for the genetic mechanism behind persistence. However, other authors argue that there is no such mechanism and that persistence results from inadvertent cell errors. In this case, the persistent population should decay according to a power-law with a particular exponent of −2. Studying persisters’ decay is, therefore, a valuable way to understand persistence. Here we simulated the fate of susceptible cells in laboratory experiments in the context of indirect resistance. Eventually, under indirect resistance, detoxifying drug-resistant cells save the persister cells that leave the dormant state and resume growth. The simulations presented here show that, by assuming a power-law decline, the exponent is close to −2, which is the expe...

Journal of Health Psychology

Attachment security has been associated with health status and symptom reporting. In this longitu... more Attachment security has been associated with health status and symptom reporting. In this longitudinal study, we investigated the association between antibiotics uptake by infants at 9-months and mother-infant attachment at 12-months. Logistic regression analyses indicated that lower maternal sensitivity was associated with increased odds of antibiotic uptake. Furthermore, 89.7% of insecure-ambivalent infants consumed antibiotics, which contrasted with 32.5% of avoidant infants and 21.5% of secure infants. This study suggests that maternal behavior and mother-infant attachment impact on antibiotic consumption, which is worrying because antibiotics may lead to several health problems later in life and antibiotic-resistance.

Frontiers in Microbiology

Bacterial biofilms have an impact in medical and industrial environments because they often confe... more Bacterial biofilms have an impact in medical and industrial environments because they often confer protection to bacteria against harmful agents, and constitute a source from which microorganisms can disperse. Conjugative plasmids can enhance bacterial ability to form biofilms because conjugative pili act as adhesion factors. However, plasmids may interact with each other, either facilitating or inhibiting plasmid transfer. Accordingly, we asked whether effects on plasmid transfer also impacts biofilm formation. We measured biofilm formation of Escherichia coli cells harboring two plasmid types, or when the two plasmids were present in the same population but carried in different cells. Using eleven natural isolated conjugative plasmids, we confirmed that some indeed promote biofilm formation and, importantly, that this ability is correlated with conjugative efficiency. Further we studied the effect of plasmid pairs on biofilm formation. We observed increased biofilm formation in approximately half of the combinations when both plasmids inhabited the same cell or when the plasmids were carried in different cells. Moreover, in approximately half of the combinations, independent of the co-inhabitation conditions, one of the plasmids alone determined the extent of biofilm formation-thus having a dominant effect over the other plasmid. The molecular mechanisms responsible for these interactions were not evaluated here and future research is required to elucidate them.

Antibiotics have been used on a large scale in veterinary and medical contexts. The massive and c... more Antibiotics have been used on a large scale in veterinary and medical contexts. The massive and continuous exposure to antimicrobial drugs has led to the emergence and spread of antibiotic resistance, which is nowadays one of the greatest threats to public health. Although antibiotics are used to treat bacterial infections, it is not only pathogenic bacteria that are affected. Upon exposure to antimicrobial drugs, bacteria that are resistant to the antibiotic administered are selected. Therefore, resistance and pathogenicity may be associated. It was recently shown that there is a positive correlation between the diversity of antibiotic resistance genes and the diversity of pathogenicity genes in human metagenomes from different geographical origins. Our study aimed to understand the factors that lead to the establishment of this positive correlation in human populations using computer simulations. Our results suggest that this positive correlation emerges if the contagion probabili...

mSphere

Human beings have used large amounts of antibiotics, not only in medical contexts but also, for e... more Human beings have used large amounts of antibiotics, not only in medical contexts but also, for example, as growth factors in agriculture and livestock, resulting in the contamination of the environment. Even when pathogenic bacteria are the targets of antibiotics, hundreds of nonpathogenic bacterial species are affected as well. Therefore, both pathogenic and nonpathogenic bacteria have gradually become resistant to antibiotics. We tested whether there is still cooccurrence of resistance and virulence determinants. We performed a comparative study of environmental and human gut metagenomes from different individuals and from distinct human populations across the world. We found a great diversity of antibiotic resistance determinants (AR diversity [ARd]) and virulence factors (VF diversity [VFd]) in metagenomes. Importantly there is a correlation between ARd and VFd, even after correcting for protein family richness. In the human gut, there are less ARd and VFd than in more diversif...

Plasmid

Plasmids are genetic elements that play a role in bacterial evolution by providing new genes that... more Plasmids are genetic elements that play a role in bacterial evolution by providing new genes that promote adaptation to diverse conditions. Plasmids are also known to reduce bacterial competitiveness in the absence of selection for plasmid-encoded traits. It is easier to understand plasmid persistence when considering the evidence that plasmid maintenance can improve during co-evolution with the bacterial host, i.e. the chromosome. However, bacteria isolated from nature often harbor diverse mobile elements: phages, transposons, genomic islands and even other plasmids. Recent interest has emerged on the role such elements play on the persistence and evolution of plasmids. Here, we mainly review interactions between different plasmids, but also discuss their interactions with other genetic elements. We focus on interactions that impact fundamental plasmid traits, such as the fitness effect imposed on their hosts and the transfer efficiency into new host cells. We illustrate these phenomena with examples concerning clinically relevant organisms and the spread of plasmids carrying antibiotic resistance genes and virulence factors.

Human beings have used large amounts of antibiotics, not only in medical contexts but also, for e... more Human beings have used large amounts of antibiotics, not only in medical contexts but also, for example, as growth factors in agriculture and livestock, resulting in the contamination of the environment. Even when pathogenic bacteria are the targets of antibiotics, hundreds of non-pathogenic bacterial species are affected as well. Therefore, both pathogenic and non-pathogenic bacteria have gradually become resistant to antibiotics. We tested whether there is still co-occurrence of resistance and virulence determinants. We performed a comparative study of environmental and human gut metagenomes issuing from different individuals and from distinct human populations across the world. We found a great diversity of antibiotic resistance determinants (ARd) and virulence factors (VFd) in metagenomes. Importantly there is a correlation between ARd and VFd, even after correcting for protein family richness. In the human gut there are less ARd and VFd than in more diversified environments, an...

Plasmid

Naturally occurring plasmids have medical importance given that they frequently code for virulenc... more Naturally occurring plasmids have medical importance given that they frequently code for virulence or antibiotic resistance. In many cases, plasmids impose a fitness cost to their hosts, meaning that the growth rate of plasmid-bearing cells is lower than that of plasmid-free cells. However, this does not fit with the fact that plasmids are ubiquitous in nature nor that plasmids and their hosts adapt to each other very fast - as has been shown in laboratory evolutionary assays. Even when plasmids are costly, they seem to largely interact in such a way that the cost of two plasmids is lower than the cost of one of them alone. Moreover, it has been argued that transfer rates are too low to compensate for plasmid costs and segregation. Several mechanisms involving interactions between plasmids and other replicons could overcome this limitation, hence contributing to the maintenance of plasmids in bacterial populations. We examine the importance of these mechanisms from a clinical point of view, particularly the spread of antibiotic resistance genes.

Bulletin of Mathematical Biology

Humans are often colonized by polymorphic bacteria such as Streptococcus pneumoniae, Bordetella p... more Humans are often colonized by polymorphic bacteria such as Streptococcus pneumoniae, Bordetella pertussis, Staphylococcus Aureus, and Haemophilus influenzae. Two co-colonizing pathogen clones may interact with each other upon host entry and during within-host dynamics, ranging from competition to facilitation. Here we examine the significance of these exploitation strategies for bacterial spread and persistence in host populations. We model SIS epidemiological dynamics to capture the global behavior of such multi-strain systems, focusing on different parameters of single and dual colonization. We analyze the impact of heterogeneity in clearance and transmission rates of single and dual colonization and find the criteria under which these asymmetries enhance endemic persistence. We obtain a backward bifurcation near R_0 = 1$$R0=1 if the reproductive value of the parasite in dually infected hosts is sufficiently higher than that in singly infected ones. In such cases, the parasite is able to persist even in sub-threshold conditions, and reducing the basic reproduction number below 1 would be insufficient for elimination. The fitness superiority in co-colonized hosts can be attained by lowering net parasite clearance rate ($$\gamma _\mathrm{{d}}$$γd), by increasing transmission rate ($$\beta _\mathrm{{d}}$$βd), or both, and coupling between these traits critically constrains opportunities of pathogen survival in the R_0<1$$R0<1 regime. Finally, using an adaptive dynamics approach, we verify that despite their importance for sub-threshold endemicity, traits expressed exclusively in coinfection should generally evolve independently of single infection traits. In particular, for \beta _\mathrm{{d}}$$βd a saturating parabolic or hyperbolic function of \gamma _\mathrm{{d}}$$γd, co-colonization traits evolve to an intermediate optimum (evolutionarily stable strategy, ESS), determined only by host lifespan and the trade-off parameters linking \beta _\mathrm{{d}}$$βd and \gamma _\mathrm{{d}}$$γd. Our study invites more empirical attention to the dynamics and evolution of parasite life-history traits expressed exclusively in coinfection.

Plasmid

Conjugative plasmids encode genes that enable them to transfer, by conjugation, from a given host... more Conjugative plasmids encode genes that enable them to transfer, by conjugation, from a given host cell to another cell. Conjugative transfer, despite being an important feature of conjugative plasmids, is not constitutive for most plasmids, the reason being that genes involved in horizontal transfer are mostly repressed. Only upon their transient de-repression are plasmids able to transfer horizontally. If host cells harbour multiple plasmids, their simultaneous transfer depends on simultaneous transient de-repression of all plasmids. If de-repression of different plasmids was random and independent events, simultaneous de-repression should be a rare event because the probability of simultaneous de-repression would be the product of the probabilities of de-repression of each plasmid. Some previous observations support this hypothesis, while others show that co-transfer of plasmids is more frequent than this reasoning indicates. Here, we show that co-transfer of multiple plasmids mainly results from non-independent events: the probability that all plasmids within a cell become de-repressed is much higher than if de-repression of plasmids genes were independent. We found a simple model for the probability of co-transfer: the plasmid having the lowest conjugation rates is the one who limits co-transfer. In this sense, cells receiving the plasmid with the lower transfer rate also receive the other plasmid. If de-repression happens simultaneously on co-resident plasmids, common cues may stimulate de-repression of distinct plasmids.