José Ponciano | University of Florida (original) (raw)

Papers by José Ponciano

Genetics, 2004

Temporarily discontinuing the use of antibiotics has been proposed as a means to eliminate resist... more Temporarily discontinuing the use of antibiotics has been proposed as a means to eliminate resistant bacteria by allowing sensitive clones to sweep through the population. In this study, we monitored a tetracycline-sensitive subpopulation that emerged during experimental evolution of E. coli K12 MG1655 carrying the multiresistance plasmid pB10 in the absence of antibiotics. The fraction of tetracyclinesensitive mutants increased slowly over 500 generations from 0.1 to 7%, and loss of resistance could be attributed to a recombination event that caused deletion of the tet operon. To help understand the population dynamics of these mutants, three mathematical models were developed that took into consideration recurrent mutations, increased host fitness (selection), or a combination of both mechanisms (full model). The data were best explained by the full model, which estimated a high mutation frequency ( ϭ 3.11 ϫ 10 Ϫ5 ) and a significant but small selection coefficient ( ϭ 0.007). This study emphasized the combined use of experimental data, mathematical models, and statistical methods to better understand and predict the dynamics of evolving bacterial populations, more specifically the possible consequences of discontinuing the use of antibiotics. Corresponding author: Department of Biological Sciences, 252 Life senting a clear selective sweep. These studies suggest Sciences S., 1132 L. De Gelder et al. et al. 1966) in 50-ml flasks, which were shaken at 225 rpm at population after ending antibiotic treatment. In con-30Њ. This medium supported a stationary-phase density of trast, other reports have clearly shown that coevolution ‫4ف‬ ϫ 10 9 /ml. Five lineages were founded from E. coli between plasmid-encoded genes and the host (Lenski K12(pB10) and five from E. coli K12::Km(pB10). Every 24 hr, et al. 1994) or compensatory mutations (Schrag et al. 39 l of each population was transferred to fresh media. The regime permitted 8 generations of binary fission every day. 1997; Andersson and Levin 1999) may result in resis-At 100-generation intervals a 1-ml sample of each population tant strains being equally as fit as or even fitter than was mixed with 0.3 ml glycerol and archived at Ϫ80Њ. The their sensitive counterparts. founding populations were archived in the same way.

Horizontal plasmid transfer plays a key role in bacterial adaptation. In harsh environments, bact... more Horizontal plasmid transfer plays a key role in bacterial adaptation. In harsh environments, bacterial populations adapt by sampling genetic material from a horizontal gene pool through self-transmissible plasmids, and that allows persistence of these mobile genetic elements. In the absence of selection for plasmid-encoded traits it is not well understood if and how plasmids persist in bacterial communities. Here we

Applied and environmental microbiology, 2005

We present a novel application of a stochastic ecological model to the study and analysis of micr... more We present a novel application of a stochastic ecological model to the study and analysis of microbial growth dynamics as influenced by environmental conditions in an extensive experimental data set. The model proved to be useful in bridging the gap between theoretical ideas in ecology and an applied problem in microbiology. The data consisted of recorded growth curves of Escherichia coli grown in triplicate in a base medium with all 32 possible combinations of five supplements: glucose, NH(4)Cl, HCl, EDTA, and NaCl. The potential complexity of 2(5) experimental treatments and their effects was reduced to 2(2) as just the metal chelator EDTA, the presumed osmotic pressure imposed by NaCl, and the interaction between these two factors were enough to explain the variability seen in the data. The statistical analysis showed that the positive and negative effects of the five chemical supplements and their combinations were directly translated into an increase or decrease in time require...

Proceedings of the National Academy of Sciences, 2015

Author contributions: J.M.F. and J.M.P. designed research; J.M.F. performed research; J.M.F. and ... more Author contributions: J.M.F. and J.M.P. designed research; J.M.F. performed research; J.M.F. and J.M.P. analyzed and interpreted results; and J.M.F. and J.M.P. wrote the paper.

PLoS Computational Biology, 2011

In this paper we used a general stochastic processes framework to derive from first principles th... more In this paper we used a general stochastic processes framework to derive from first principles the incidence rate function that characterizes epidemic models. We investigate a particular case, the Liu-Hethcote-van den Driessche's (LHD) incidence rate function, which results from modeling the number of successful transmission encounters as a pure birth process. This derivation also takes into account heterogeneity in the population with regard to the per individual transmission probability. We adjusted a deterministic SIRS model with both the classical and the LHD incidence rate functions to time series of the number of children infected with syncytial respiratory virus in Banjul, Gambia and Turku, Finland. We also adjusted a deterministic SEIR model with both incidence rate functions to the famous measles data sets from the UK cities of London and Birmingham. Two lines of evidence supported our conclusion that the model with the LHD incidence rate may very well be a better description of the seasonal epidemic processes studied here. First, our model was repeatedly selected as best according to two different information criteria and two different likelihood formulations. The second line of evidence is qualitative in nature: contrary to what the SIRS model with classical incidence rate predicts, the solution of the deterministic SIRS model with LHD incidence rate will reach either the disease free equilibrium or the endemic equilibrium depending on the initial conditions. These findings along with computer intensive simulations of the models' Poincaré map with environmental stochasticity contributed to attain a clear separation of the roles of the environmental forcing and the mechanics of the disease transmission in shaping seasonal epidemics dynamics.

Journal of Mathematical Biology, 2005

Antibiotic resistant bacteria are a constant threat in the battle against infectious diseases. On... more Antibiotic resistant bacteria are a constant threat in the battle against infectious diseases. One strategy for reducing their effect is to temporarily discontinue the use of certain antibiotics in the hope that in the absence of the antibiotic the resistant strains will be replaced by the sensitive strains. An experiment where this strategy is employed in vitro produces data which showed a slow accumulation of sensitive mutants. Here we propose a mathematical model and statistical analysis to explain this data.

Genetics, 2006

Genetics, 2008

Little is known about the range of hosts in which broad-host-range (BHR) plasmids can persist in ... more Little is known about the range of hosts in which broad-host-range (BHR) plasmids can persist in the absence of selection for plasmid-encoded traits, and whether this ''long-term host range'' can evolve over time. Previously, the BHR multidrug resistance plasmid pB10 was shown to be highly unstable in Stenotrophomonas maltophilia P21 and Pseudomonas putida H2. To investigate whether this plasmid can adapt to such unfavorable hosts, we performed evolution experiments wherein pB10 was maintained in strain P21, strain H2, and alternatingly in P21 and H2. Plasmids that evolved in P21 and in both hosts showed increased stability and decreased cost in ancestral host P21. However, the latter group showed higher variability in stability patterns, suggesting that regular switching between distinct hosts hampered adaptive plasmid evolution. The plasmids evolved in P21 were also equally or more stable in other hosts compared to pB10, which suggested true host-range expansion. The complete genome sequences of four evolved plasmids with improved stability showed only one or two genetic changes. The stability of plasmids evolved in H2 improved only in their coevolved hosts, not in the ancestral host. Thus a BHR plasmid can adapt to an unfavorable host and thereby expand its long-term host range.

Ecology, 2009

Hierarchical statistical models are increasingly being used to describe complex ecological proces... more Hierarchical statistical models are increasingly being used to describe complex ecological processes. The data cloning (DC) method is a new general technique that uses Markov chain Monte Carlo (MCMC) algorithms to compute maximum likelihood (ML) estimates along with their asymptotic variance estimates for hierarchical models. Despite its generality, the method has two inferential limitations. First, it only provides Wald-type confidence intervals, known to be inaccurate in small samples. Second, it only yields ML parameter estimates, but not the maximized likelihood values used for profile likelihood intervals, likelihood ratio hypothesis tests, and information-theoretic model selection. Here we describe how to overcome these inferential limitations with a computationally efficient method for calculating likelihood ratios via data cloning. The ability to calculate likelihood ratios allows one to do hypothesis tests, construct accurate confidence intervals and undertake information-based model selection with hierarchical models in a frequentist context. To demonstrate the use of these tools with complex ecological models, we reanalyze part of Gause's classic Paramecium data with state-space population models containing both environmental noise and sampling error. The analysis results include improved confidence intervals for parameters, a hypothesis test of laboratory replication, and a comparison of the Beverton-Holt and the Ricker growth forms based on a model selection index.

Ecology, 2010

Observation or sampling error in population monitoring can cause serious degradation of the infer... more Observation or sampling error in population monitoring can cause serious degradation of the inferences, such as estimates of trend or risk, that ecologists and managers frequently seek to make with time-series observations of population abundances. We show that replicating the sampling process can considerably improve the information obtained from population monitoring. At each sampling time the sampling method would be repeated, either simultaneously or within a short time. In this study we examine the potential value of replicated sampling to population monitoring using a density-dependent population model. We modify an existing population time-series model, the Gompertz state-space model, to incorporate replicated sampling, and we develop maximum-likelihood and restricted maximum-likelihood estimates of model parameters. Depending on sampling protocols, replication may or may not entail substantial extra cost. Some sampling programs already have replicated samples, but the samples are aggregated or pooled into one estimate of population abundance; such practice of aggregating samples, according to our model, loses considerable information about model parameters. The gains from replicated sampling are realized in substantially improved statistical inferences about model parameters, especially inferences for sorting out the contributions of process noise and observation error to observed population variability.

Ecological Monographs, 2006

We describe a discrete-time, stochastic population model with density dependence, environmental-t... more We describe a discrete-time, stochastic population model with density dependence, environmental-type process noise, and lognormal observation or sampling error. The model, a stochastic version of the Gompertz model, can be transformed into a linear Gaussian state-space model (Kalman filter) for convenient fitting to time series data. The model has a multivariate normal likelihood function and is simple enough for a variety of uses ranging from theoretical study of parameter estimation issues to routine data analyses in population monitoring. A special case of the model is the discrete-time, stochastic exponential growth model (density independence) with environmental-type process error and lognormal observation error.

Applied and Environmental Microbiology, 2009

The stochastic Ricker population model was used to investigate the generation and maintenance of ... more The stochastic Ricker population model was used to investigate the generation and maintenance of genetic diversity in a bacterial population grown in a spatially structured environment. In particular, we showed that Escherichia coli undergoes dramatic genetic diversification when grown as a biofilm. Using a novel biofilm entrapment method, we retrieved 64 clones from each of six different depths of a mature biofilm, and after subculturing for ϳ30 generations, we measured their growth kinetics in three different media. We fit a stochastic Ricker population growth model to the recorded growth curves. The growth kinetics of clonal lineages descendant from cells sampled at different biofilm depths varied as a function of both the depth in the biofilm and the growth medium used. We concluded that differences in the growth dynamics of clones were heritable and arose during adaptive evolution under local conditions in a spatially heterogeneous environment. We postulate that under nutrient-limited conditions, selective sweeps would be protracted and would be insufficient to purge less-fit variants, a phenomenon that would allow the coexistence of genetically distinct clones. These findings contribute to the current understanding of biofilm ecology and complement current hypotheses for the maintenance and generation of microbial diversity in spatially structured environments.

Microbiology, 2007

Broad-host-range (BHR) IncP-1 plasmids have the ability to transfer between and replicate in near... more Broad-host-range (BHR) IncP-1 plasmids have the ability to transfer between and replicate in nearly all species of the Alpha-, Beta-and Gammaproteobacteria, but surprisingly few data are available on the stability of these plasmids in strains within their host range. Moreover, even though molecular interactions between the bacterial host and its plasmid(s) exist, no systematic study to date has compared the stability of the same plasmid among different hosts. The goal of this study was to examine whether the stability characteristics of an IncP-1 plasmid can be variable between strains within the host range of the plasmid. Therefore, 19 strains within the Alpha-, Beta-or Gammaproteobacteria carrying the IncP-1b plasmid pB10 were serially propagated in non-selective medium and the fraction of segregants was monitored through replica-picking. Remarkably, a large variation in the stability of pB10 in different strains was found, even between strains within the same genus or species. Ten strains showed no detectable plasmid loss over about 200 generations, and in two strains plasmid-free clones were only sporadically observed. In contrast, three strains, Pseudomonas koreensis R28, Pseudomonas putida H2 and Stenotrophomonas maltophilia P21, exhibited rapid plasmid loss within 80 generations. Parameter estimation after mathematical modelling of these stability data suggested high frequencies of segregation (about 0.04 per generation) or high plasmid cost (i.e. a relative fitness decrease in plasmid-bearing cells of about 15 and 40 %), which was confirmed experimentally. The models also suggested that plasmid reuptake by conjugation only played a significant role in plasmid stability in one of the three strains. Four of the 19 strains lost the plasmid very slowly over about 600 generations. The erratic decrease of the plasmid-containing fraction and simulation of the data with a new mathematical model suggested that plasmid cost was variable over time due to compensatory mutations. The findings of this study demonstrate that the ability of a so-called 'BHR' plasmid to persist in a bacterial population is influenced by strain-specific traits, and therefore observations made for one strain should not be generalized for the entire species or genus.