Biology subjects

Worthan, S. B.

Publications and source records attributed to Worthan, S. B..

3 recordsLinked to original sources

bioRxiv2024

Evolution of pH-sensitive transcription termination during adaptation to repeated long-term starvation.

Fluctuating environments that consist of regular cycles of co-occurring stress are a common challenge faced by cellular populations. For a population to thrive in constantly changing conditions, an ability to coordinate a rapid cellular response is essential. Here, we identify a mutation conferring an arginine-to-histidine (Arg to His) substitution in the transcription terminator Rho. The rho R109H mutation frequently arose in E. coli populations experimentally evolved under repeated long-term starvation conditions, during which feast and famine result in drastic environmental pH fluctuations. Metagenomic sequencing revealed that populations containing the rho mutation also possess putative loss-of-function mutations in ydcI, which encodes a recently characterized transcription factor associated with pH homeostasis. Genetic reconstructions of these mutations show that the rho allele confers a plastic alkaline-induced reduction of Rho function that, when found in tandem with a {Delta}ydcI allele, leads to intracellular alkalinization and genetic assimilation of Rho mutant function. We further identify Arg to His substitutions at analogous sites in rho alleles from species originating from fluctuating alkaline environments. Our results suggest that Arg to His substitutions in global regulators of gene expression can serve to rapidly coordinate complex responses through pH sensing and shed light on how cellular populations across the tree of life use environmental cues to coordinate rapid responses to complex, fluctuating environments.

microbiology↗

bioRxiv2023

Trade-offs, trade-ups, and high mutational parallelism underlie microbial adaptation to extreme feast/famine

Microbes are robust organisms capable of rapidly adapting to complex stress, enabling the colonization of harsh environments. In nature, microbes are regularly challenged by starvation, which is a particularly complex stress because resource limitation often co-occurs with changes in pH, osmolarity, and toxin accumulation created by metabolic waste. Often overlooked are the additional complications introduced by eventual resource replenishment as successful microbes must withstand rapid environmental shifts before swiftly capitalizing on replenished resources to avoid invasion by competing species. To understand how microbes navigate trade-offs between growth and survival, ultimately adapting to thrive in environments with extreme fluctuations, we experimentally evolved 16 Escherichia coli populations for 900 days to repeated feast/famine cycles of 100-day starvation before resource replenishment. Using longitudinal population-genomic analysis, we found that evolution in response to extreme feast/famine is characterized by narrow adaptive trajectories with high mutational parallelism and notable mutational order. Genetic reconstructions reveal that early mutations result in trade-offs for biofilm and motility but trade-ups for growth and survival, as these mutations conferred correlated advantages during both short-term and long-term culture. Our results demonstrate how microbes can navigate the adaptive landscapes of regularly fluctuating conditions and ultimately follow mutational trajectories that confer benefits across diverse environments.

evolutionary biology↗

bioRxiv2021

A ribosomal protein variant that confers macrolide resistance differentially regulates acid resistance, catabolism, and biofilm formation related genes in Escherichia coli

Mutational changes in bacterial ribosomes that confer antibiotic resistance decrease cell fitness. Determining the genetic factors that interconnect antibiotic resistance and cell fitness is critical in the fight against bacterial infections. Here, we describe gene expression and phenotypic changes presented in Escherichia coli cells carrying an uL22(K90D) mutant ribosomal protein, which showed growth defects and resistance to macrolide antibiotics. Ribosome profiling analyses revealed reduced expression of operons involved in catabolism, electron transportation, indole production, and lysine-decarboxylase acid resistance. In general, ribosome occupancy was increased at rare codons while translation initiation of proximal genes in several of the affected operons was substantially reduced. Decline of the activity of these genes was accompanied by increased expression of macrolide multidrug efflux pumps, the glutamate-decarboxylase regulon, and the autoinducer-2 metabolic regulon. In concordance with these changes, uL22(K90D) mutant cells grew better in acidic conditions and generated more biofilm in static cultures than their parental strain. Our work provides new insights on how mutations in ribosomal proteins induce the acquisition of macrolide and pH resistance, and increase the ability to generate biofilms.

genomics↗