Libertad Garcia-Villada

National Institute of Environmental Health Sciences | NIEHS · Laboratory of Genome Integrity and Structural Biology

Pseudomonas aeruginosa is a major cause of nosocomial infections and the leading cause of chronic lung infections in cystic fibrosis and chronic obstructive pulmonary disease patients. Antibiotic treatment remains challenging because P. aeruginosa is resistant to high concentrations of antibiotics and has a remarkable ability to acquire mutations c...

Evolution of antibiotic resistance is a world health crisis, fueled by new mutations. Drugs to slow mutagenesis could, as cotherapies, prolong the shelf-life of antibiotics, yet evolution-slowing drugs and drug targets have been underexplored and ineffective. Here, we used a network-based strategy to identify drugs that block hubs of fluoroquinolon...

Antibiotic resistance is a global health threat and often results from new mutations. Antibiotics can induce mutations via mechanisms activated by stress responses, which both reveal environmental cues of mutagenesis and are weak links in mutagenesis networks. Network inhibition could slow the evolution of resistance during antibiotic therapies. De...

Antibiotics can induce mutations that cause antibiotic resistance, triggered by stress responses. The identities of the stress-response activators reveal environmental cues that elicit mutagenesis, and are weak links in mutagenesis networks, inhibition of which could slow evolution of resistance during antibiotic therapies. Despite pivotal importan...

Antibiotics can induce mutations that cause antibiotic resistance. Yet, despite their importance, mechanisms of antibiotic-promoted mutagenesis remain elusive. We report that the fluoroquinolone antibiotic ciprofloxacin (cipro) induces mutations by triggering transient differentiation of a mutant-generating cell subpopulation, using reactive oxygen...

Antibiotics can induce mutations that cause antibiotic resistance. Yet, despite their importance, mechanisms of antibiotic-promoted mutagenesis remain elusive. We report that the fluoroquinolone antibiotic ciprofloxacin (cipro) induces mutations by triggering transient differentiation of a mutantgenerating cell subpopulation, using reactive oxygen...

Antibiotics can induce mutations that cause antibiotic resistance. Yet, despite their importance, mechanisms of antibiotic-promoted mutagenesis remain elusive. We report that the fluoroquinolone antibiotic ciprofloxacin (cipro) induces mutations that cause drug resistance by triggering differentiation of a mutant-generating cell subpopulation, usin...

Understanding virus evolution is key for improving ways to counteract virus-borne diseases. Results from comparative analyses have previously suggested a trade-off between fecundity and lifespan for viruses that infect the bacterium Escherichia coli (i.e. for coliphages), which, if confirmed, would define a particular constraint on the evolution of...

Parameters of the sigmoidal curves fitted to the RTIN and RTSUB one-step curves shown in Figure S2. (DOC)

Primers and PCR cycling parameters for amplifying and sequencing. (DOC)

Probability that a new RT mutation with selection coefficient s is lost during plaque growth in a host lawn. The black line represents the estimations for μg = 0.039 while the gray line represents the estimations for μg = 0.287. (TIF)

One-step curves for RTIN and RTSUB. Three independent curves were obtained per RT mutant. In all cases, the first bursts appeared between 30 and 40 min after infection. If the 20 min allowed for adsorption are also considered, it means that Qß requires a minimum of 50 to 60 min to complete an infection cycle in RTH cells. Thus, if any of the progen...

Riboviruses (RNA viruses without DNA replication intermediates) are the most abundant pathogens infecting animals and plants. Only a few riboviral infections can be controlled with antiviral drugs, mainly because of the rapid appearance of resistance mutations. Little reliable information is available concerning i) kinds and relative frequencies of...

Available DNA mutational spectra reveal that the number of mutants with multiple mutations ("multiples") is usually greater than expected from a random distribution of mutations among mutants. These overloads imply the occurrence of non-random clusters of mutations, probably generated during episodes of low-fidelity DNA synthesis. Excess multiples...

We investigated the occurrence of tolerance to atrazine (2-chloro-4-ethylamino-6-isopropylamino-s-triazine) in soil microalgae by means of the pollution-induced community tolerance methodology. To this end, a natural soil assemblage of microalgae, reared under laboratory conditions, was used as experimental model. Experimental cultures were exposed...

Phenotypic evolution in microalgae: a dramatic morphological shift in Dictyosphaerium chlorelloides (Chlorophyta) after exposure to TNT. The occurrence of rapid morphological evolution in the microalga Dictyosphaerium chlorelloides (Chlorophyta) was induced after exposure of the wild strains of the alga to the potent algal poison 2,4,6-trinitrotolu...

Phenotypic expression of traits is the result of complex interactions between genotype and environment. A combination of experiments and statistics based on restricted maximum likelihood (REML) procedures was utilised for estimating the proportion of genetic variability in a series of phenotypic characters (microcystin net production, cell size, da...

No abstract available.

Neospora caninum, a recently recognized protozoan parasite of animals, is considered to be a major cause of bovine abortion worldwide. Although its life cycle is not completely known, recent studies suggest that the sexual stage occurs in dogs. The prevalence of sexual reproduction in N. caninum, however, is unknown. We investigated the ability of...

Adaptation of Spirogyra insignis (Chlorophyceae) to growth and survival in an extreme natural environment (sulphureous waters from La Hedionda Spa, S. Spain) was analysed by using an experimental model. Photosynthesis and growth of the alga were inhibited when it was cultured in La Hedionda Spa waters (LHW), but after further incubation for several...

A new genetic approach was developed for increasing specificity of microalgal biosensors. This method is based on the use of two different genotypes jointly to detect a given pollutant: (i) a sensitive genotype to obtain sensitivity; and (ii) a resistant mutant to obtain specificity. The method was tested by the development of a microalgal biosenso...

Freshwater toxic cyanobacteria are an increasing problem to human and animal health. Control of cyanobacteria in water supply reservoirs involves the use of algaecides, such as copper sulphate, usually in a repetitive way. Repercussions of recurrent algaecide treatments on cyanobacteria population dynamics remain still unknown. We studied the adapt...

The toxic spill of acid wastes rich in heavy metals/metalloids (AWHM) from the Aznalcóllar mine in April 1998, threatening the Doñana National Park, is considered to be the worst environmental disaster related to acute pollution in Spanish history. The aim of this work was to study the adaptation of microalgae (which play an important role as prima...

The increasing rates of global extinction due to human activities necessitate studies of the ability of organisms to adapt to the new environmental conditions resulting from human disturbances. We investigated the evolutionary adaptation of a microalga to sudden environmental change resulting from exposure to novel toxic chemical residues. A labora...

Residues contribute to water pollution and pose a challenge to microalgal populations because numerous contaminants are toxic to microalgae, even in the micromolar range. Adaptation of microalgae from herbicide sensitivity to herbicide resistance was analysed by an ecological genetic approach, using the unicellular alga Dictyosphaerium chlorelloide...