Biology subjects

Balbontin, R.

Publications and source records attributed to Balbontin, R..

3 recordsLinked to original sources

bioRxiv2025

Lack of RNase HI affects virulence in Salmonella enterica

Bacterial virulence and antibiotic resistance are interconnected global threats that can synergize to multiply their adverse effects on health and economy. Two proposed strategies to address this dual challenge are non-biocidal inhibition of virulence traits (anti-virulence strategy) and manipulation of eco-evolutionary dynamics in bacterial populations to hinder dissemination of antibiotic resistance (anti-resistance strategy). Both strategies require identifying factors involved in bacterial gene expression, fitness and evolution. R-loops strongly influence these traits, as well as fitness of bacteria carrying antibiotic resistance mutations. This makes the enzyme responsible for R-loop degradation, the RNase HI, a promising target for anti-resistance approaches. Interestingly, the involvement of R-loops in gene expression could also make RNase HI a potential target for anti-virulence strategies. In this study, we explored this possibility by investigating the effects of RNase HI deficiency on the pathogenicity of Salmonella enterica. We found that the absence of RNase HI alters the expression of genes associated with virulence both at the population and single-cell levels, and both ex vivo and during infection of mammalian cells. Furthermore, we observed that RNase HI depletion causes defects in phenotypes associated with virulence, such as motility and biofilm formation. Lack of RNase HI also reduces the ability of Salmonella to survive within macrophages. However, lack of RNase HI does not significantly affect the invasion of mammalian epithelial cells or their immune response. Overall, our results demonstrate a pleiotropic influence of R-loops on bacterial virulence, suggesting that RNase HI could be a target for anti-virulence strategies. These findings provide a theoretical framework for the development of dual anti-resistance and anti-virulence interventions based on RNase HI targeting.

microbiology↗

bioRxiv2019

DNA breaks are key contributors to the cost of antibiotic resistance

Antibiotic resistance often generates a fitness cost to bacteria in drug-free environments. Understanding the causes of the cost is considered the Holy Grail in the antibiotic resistance field, as it is the main determinant of the prevalence of resistances upon reducing antibiotics use. We show that DNA breaks can explain most of the variation in the cost of resistances common in pathogens. Here we demonstrate that targeting the RNase that degrades R-loops, which cause DNA breaks, exacerbates the cost of resistance. Consequently, lack of RNase HI function drives resistant clones to extinction in populations with high initial frequency of resistance, both in laboratory conditions and in a mouse model of gut colonization. Thus, RNase HI provides a target specific against resistant bacteria, which we validate using a repurposed drug. In summary, we revealed key mechanisms underlying the cost of antibiotic resistance that can be exploited to specifically eliminate resistant bacteria.

microbiology↗

bioRxiv2017

Cheating on orthogonal social traits prevents the tragedy of the commons in Pseudomonas aeruginosa

Bacterial cooperation can be disrupted by non-producers, which can profit from public goods without paying their production cost. A cheater can increase in frequency, exhausting the public good and causing a population collapse. Here we investigate how interactions among two cheaters for distinct social traits influence the short and long-term dynamics of polymorphic populations. Using as a model Pseudomonas aeruginosa and its extensively studied social traits, production of the siderophore pyoverdine and the quorum sensing regulated elastase, we analyzed the social dynamics of polymorphic populations under conditions where the two traits are required for optimal growth. We show that cheaters for either trait compete with both the wild type and each other, and that mutants for pyoverdine production can prevent a drastic population collapse caused by quorum sensing cheaters. A simple mathematical model suggests that the observed social dynamics are determined by the ratio of the costs of each social trait, such that the mutant which avoids paying the highest cost dominates the population. Finally, we demonstrate how quorum sensing regulation can avoid the full loss of cooperation.

genomics↗