Prophages, viral sequences integrated into bacterial genomes, can be beneficial and costly. Despite the risk of prophage activation subsequent death, active prophages are present in most genomes. However, our understanding selective forces that maintain populations is limited. Combining experimental evolution with stochastic modeling, we show maintenance loss primarily determined by environmental conditions alter net fitness effect a on its host. When too costly, they rapidly lost through...

The success of antimicrobial treatment is threatened by the evolution drug resistance. Population genetic models are an important tool in mitigating that threat. However, most such consider resistance emergence via a single mutational step. Here, we assembled experimental evidence follows two patterns: (i) mutation, which provides large benefit, or (ii) multiple mutations, each conferring small combine to yield high-level Using stochastic modeling, then investigated consequences these...

Antibiotic resistance spread via plasmids is a serious threat to successfully fight infections and makes understanding plasmid transfer in nature crucial prevent the rise of antibiotic resistance. Studies addressing dynamics conjugation have yet neglected one omnipresent factor: prophages (viruses integrated into bacterial genomes), whose activation can kill host surrounding cells. To investigate impact on conjugation, we combined experiments mathematical modelling. Using Escherichia coli,...

Changes in gene expression are an important mode of evolution; however, the proximate mechanism these changes is poorly understood. In particular, little known about effects mutations within cis binding sites for transcription factors, or nature epistatic interactions between mutations. Here, we tested single and double mutants two involved transcriptional regulation Escherichia coli araBAD operon, a component arabinose metabolism, using synthetic system. This system decouples control from...

Pharmacokinetic-pharmacodynamic (PKPD) models, which describe how drug concentrations change over time and that affects pathogen growth, have proven highly valuable in designing optimal treatments aimed at bacterial eradication. However, the fast rise of antimicrobial resistance calls for increased focus on an additional treatment optimization criterion: avoidance evolution. We demonstrate here coupling PKPD population genetics models can be used to determine regimens minimize potential...

To curb the rising threat of antimicrobial resistance, we need to understand routes treatment failure. Bacteria can survive by using both genetic and phenotypic mechanisms diminish effect antimicrobials. We assemble empirical data showing that, for example, Pseudomonas aeruginosa infections frequently contain persisters, transiently non-growing cells unaffected antibiotics (AB) hyper-mutators, mutants with elevated mutation rates, thus higher probability resistance emergence. Resistance,...

Abstract Prophages, viral sequences integrated into bacterial genomes, can be beneficial and costly. Despite the risk of prophage activation subsequent death, active prophages are present in most genomes. However, our understanding selective forces that maintain populations is limited. Combining experimental evolution with stochastic modelling, we show maintenance loss primarily determined by environmental conditions alter net fitness effect a prophage. When too costly, they rapidly lost...

Under stable growth conditions, bacteria maintain cell size homeostasis through coordinated elongation and division. However, fluctuations in nutrient availability result dynamic regulation of the target size. Using microscopy imaging mathematical modelling, we examine how bacterial volume changes over curve response to conditions. We find that two rod-shaped bacteria,

Mobile genetic elements (MGEs), including temperate bacteriophages and conjugative plasmids, are major vectors of virulence antibiotic resistance in bacterial populations. To maximize reproductive fitness, MGEs have to optimize horizontal vertical transmission. Yet, the cost transmission (e.g. phage lysis) puts these modes at odds. Using virulence-transmission trade-off theory, we identify three groups environmental variables affecting balance between transmission: host density, physiology,...

Abstract Antibiotic resistance spread via plasmids is a serious threat to successfully fight infections and makes understanding plasmid transfer in nature crucial prevent the rise of antibiotic resistance. Studies addressing dynamics conjugation have yet neglected one omnipresent factor: prophages (viruses integrated into bacterial genomes), whose activation can kill host surrounding cells. To investigate impact on conjugation, we combined experiments mathematical modelling. Using E. coli ,...

Gene expression is regulated by the set of transcription factors (TFs) that bind to promoter. The ensuing regulating function often represented as a combinational logic circuit, where output (gene expression) determined current input values (promoter bound TFs) only. However, simultaneous arrival TFs strong assumption, since and translation genes introduce intrinsic time delays there no global synchronisation among times different molecular species at their targets. We present an...

Abstract Reliable operation of cellular programs depends crucially on the specificity biomolecular interactions. In gene regulatory networks, appropriate expression genes is determined through specific binding transcription factors (TFs) to their cognate DNA sequences. However, large genomic background likely contains many sequences showing similarity TF target motifs, potentially allowing for substantial non-cognate with low specificity. Whether and how impacts function fitness remains...

Accessory genes, such as antibiotic resistance genes (ARGs) can spread horizontally by mobile genetic elements, including plasmids and (temperate) bacteriophages leading to increased bacterial fitness in particular environments. In contrast plasmids, temperate phages i.e. viruses that incorporate their own material into host bacteria (then called lysogen) additionally increase hosts’ through ability kill phage-susceptible competitors. However, ARG-transfer (conjugation), which has been...

Abstract The success of antimicrobial treatment is threatened by the evolution drug resistance. Population genetic models are an important tool in mitigating that threat. However, most such consider resistance emergence via a single mutational step. Here, we assembled experimental evidence follows two patterns: i) mutation, which provides large MIC increase, or ii) multiple mutations, each conferring small combine to yield high-level Using stochastic modeling then investigated consequences...

Abstract Antimicrobial resistance poses a rising threat to global health, making it crucial understand the routes of bacterial survival during antimicrobial treatments. Treatment failure can result from genetic or phenotypic mechanisms, which diminish effect antibiotics. By assembling empirical data, we find that, for example, Pseudomonas aeruginosa infections in cystic fibrosis patients frequently contain persisters, transiently non-growing and antibiotic-refractory subpopulations,...

Abstract As infectious agents of bacteria and vehicles horizontal gene transfer, plasmids play a key role in bacterial ecology evolution. Plasmid dynamics are shaped not only by plasmid-host interactions, but also ecological interactions between plasmid variants. These complex: can co-infect the same host cell consequences for co-resident be either beneficial or detrimental. Many biological processes that govern co-infection–from systems to exclude infection other regulation copy number per...