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Environmental perturbations impact multiple cellular traits, including gene expression. Bacteria respond to these stressful situations through complex gene interaction networks, thereby inducing stress tolerance and survival of cells. In this paper, we study the response mechanisms of E. coli when exposed to different environmental stressors via differential expression and co-expression analysis. Gene co-expression networks were generated and analyzed via Weighted Gene Co-expression Network Analysis (WGCNA). Based on the gene co-expression networks, genes with similar expression profiles were clustered into modules. The modules were analysed for identification of hub genes, enrichment of biological processes and transcription factors. In addition, we also studied the link between transcription factors and their differentially regulated targets to understand the regulatory mechanisms involved. These networks validate known gene interactions and provide new insights into genes mediating transcriptional regulation in specific stress environments, thus allowing for in silico hypothesis generation.

Peptides play an essential role in biotechnological applications as therapeutic and diagnostic agents due to their tunable activity for desired function. So far, a variety of peptide therapeutics and their peptide-based carriers have been engineered for drug delivery applications. However, in order to design and develop such systems for tissue-specific applications, the cellular microenvironment must be properly considered. Peptide-based materials have vast potential applications, particularly for cancer-related systems. Thus, in this chapter, we first focus on different design strategies and considerations for drug-release mechanisms in peptide-based materials. Then, we explain how tumor microenvironments may be distinguished from healthy tissue, including discussion of tumor-specific drug delivery strategies. Finally, the growing significance of peptide chemotherapeutics will be emphasized in terms of design concerns and current applications.

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Gene acquisition through horizontal gene transfer (HGT) may either exert a beneficial, neutral, or deleterious fitness effect on the recipient cell thereby determining the evolutionary fate of the newly transferred gene. The distribution of fitness effects (DFE) thus is a fundamental predictor of the outcome of an HGT event. The environment plays a considerable role in altering the fitness of a horizontally transferred gene. We have studied the DFE of genes transferred from Salmonella enterica serovar Typhimurium to Escherichia coli in six environments, that potentially represent the conditions experienced by the two species. The data suggests high variability, with some genes becoming deleterious in one environment, while becoming neutral or even beneficial in another, suggesting that fluctuating environments may increase the likelihood of HGT. The present study focuses on the DFE of genes transferred from Escherichia coli to macrophage-associated Salmonella Typhimurium strain 4/74 in four environments, that mimic the conditions inside a macrophage cell. In addition to the external environment, we are also looking at, how changes in the intrinsic environment of a cell, after an HGT event, could affect fitness. Functional similarity of the horizontally transferred gene to the endogenous copy can cause an imbalance due to increased protein dosage, thereby leading to a negative fitness effect. By comparing the growth rates of each ortholog gene with the ‘wild type’, in the four environments, we can elucidate when gene dosage acts as a barrier to HGT, helping us to understand the relationship of environmental quality and HGT, which is of evolutionary importance. We have identified 12 genes showing dosage dependent effects across the four environments, with some genes showing environment specificity, indicating an increased intolerance of the recipient to high protein dosage, making it a significant barrier to HGT. A preprint is available on bioRxiv https://doi.org/10.1101/2022.04.01.486712

Horizontal Gene Transfer (HGT) is a powerful evolutionary force facilitating bacterial adaptation and emergence of novel phenotypes. Several factors, including environmental ones, are predicted to restrict HGT, but we lack data supporting these predictions. Here, we address this gap by measuring the relative fitness of 44 genes horizontally transferred from E. coli to S. Typhimurium strain 4/74 in four infection relevant environments and estimated the distribution of fitness effects (DFE) in each environment. Roughly half of the genes, 40-50%, had significant fitness effects in at least one environment, with most genes showing significant gene by environment (G x E) interactions. We further identified 12 genes with dosage-dependent effects across the four environments, indicating that intolerance of the recipient strain to high protein dosage is a significant barrier to HGT. We also found longer genes had stronger fitness detriments than shorter ones, showing that gene length can significantly hinder HGT. In summary, a substantial fraction of transferred genes had a significant fitness cost on the recipient, with both gene characteristics and the environment providing barriers to HGT.

The evolutionary fate of a horizontal gene transfer (HGT) event is determined by its fitness on the recipient cell, i.e., whether it is beneficial, neutral or deleterious. The distribution of fitness effects (DFE), thus is a fundamental predictor of the outcome of an HGT event. The environment plays a considerable role in determining the fitness cost of a horizontally transferred gene. We have studied the fitness effects of genes transferred from Salmonella enterica serovar Typhimurium to Escherichia coli in six environments, that potentially represent the conditions experienced by the two species. The data suggests high variability of genes in different environments. Genes, whose fitness varies substantially between environments, may be able to persist in populations while being deleterious in one environment, they may be neutral or even beneficial in another environment, suggesting that environmental fluctuations may increase the likelihood of HGT. In addition to the in vitro environments, we are also looking at, how changes in the intrinsic environment of a cell, after an HGT event, could affect fitness. An increase in protein dosage due to functional similarity of the horizontally transferred gene to the endogenous gene can cause an imbalance in the cell, thereby leading to a negative fitness effect. By comparing the growth rates of each ortholog gene with the wild type strain, we can elucidate when gene dosage acts as a barrier to HGT.