Biology subjects

Petersen, M. E.

Publications and source records attributed to Petersen, M. E..

6 recordsLinked to original sources

bioRxiv2026

Negative allometry of egg size among 29 species of drosophilid flies

The body size of adults and immature stages are fundamental animal traits that influence animal physiology, ecology, and range distribution. While the importance of egg size has been acknowledged as a proxy of parental investment in animals, little work has addressed the tempo and mode of evolution of egg size and shape. Here, we present a comparative study of this trait using a phylogeny based on genome-wide markers together with measurements of egg size and adult body size from 29 drosophilid species. Our analyses revisit the allometric relationship between egg size and body size and show that egg size scales negatively with respect to adult size, even after accounting for shared evolutionary history. In other words, larger species tend to produce proportionally smaller eggs. We also detect a moderate phylogenetic signal in both egg size and egg shape, indicating that closely related species resemble each other in these traits. Model comparisons show that the evolution of egg morphology in drosophilids is best described by gradual divergence through time driven by stochastic evolutionary change. This pattern contrasts with findings from other animal groups, including birds, cephalopods, and reptiles, where alternative evolutionary models better explain trait evolution. Together, these results suggest that the evolutionary dynamics shaping egg morphology in drosophilids differ from those operating in other major lineages and underscore the importance of comparative analyses of early developmental traits across taxa.

evolutionary biology↗

bioRxiv2025

The host environment activates multiple stress responses which correlate with antibiotic tolerance in Staphylococcus aureus

Introduction. Antibiotic tolerance allows genetically susceptible bacteria to survive antibiotic exposure and contributes to treatment failure and recurrent infection. In Staphylococcus aureus, tolerance is closely associated with biofilm infections, and this association is conventionally explained by the biofilm mode of growth itself, in which mass transfer limitation is presumed to starve and arrest cells in the deeper layers. Gap Statement. That explanation rests largely on biofilms grown in rich laboratory media, and it has rarely been tested against the alternative that the host environment, rather than the biofilm architecture, drives the underlying physiological change. Furthermore, because transcriptomic and bulk fluorescence methods average across the population, they cannot establish whether stress responses are activated uniformly in all cells or strongly in a minority. Aim. To determine, at single-cell resolution, whether bacterial stress responses are activated by biofilm growth, by the host environment, or by both, and whether such activation coincides with a reduced rate of antibiotic killing. Methodology. Promoter regions of recA, katA, relQ, ilvleu and groESL were fused to a stable green fluorescent protein variant to report the SOS, oxidative stress, cell wall stress- and starvation-activated stringent, and heat shock responses. Reporter activation was quantified by confocal microscopy in exponential and stationary cultures, after defined chemical and physical stresses, in biofilms grown in tryptic soy broth, in diluted and undiluted human serum, in heat-inactivated serum, and in S. aureus internalised by human neutrophils. Tolerance was assessed as the rate of killing in time-kill assays. Results. Biofilms grown in laboratory media or in diluted serum showed minimal stress response activation, whereas biofilms of the same strain grown in undiluted human serum activated all five responses, uniformly across the population. Heat inactivation of the serum did not abolish this effect, indicating that complement and heat-labile serum enzymes are not required. One hour of serum exposure activated the stringent response via both starvation and cell wall stress, and it abolished detectable killing by ciprofloxacin, while producing only small changes in killing by vancomycin and rifampicin and none by daptomycin or dicloxacillin. Pre-treatments that activated the stringent or heat shock responses likewise arrested growth and slowed ciprofloxacin killing. Neutrophil phagocytosis activated the oxidative stress response and both stringent response branches. The host environment, rather than the biofilm mode of growth, is the dominant driver of stress response activation in S. aureus. Activation is population-wide and coincides with population-wide ciprofloxacin tolerance. Laboratory biofilm models that omit host components are therefore likely to underestimate the tolerance encountered during infection.

microbiology↗

bioRxiv2025

Flight feathers evolve fastest near the tip of the wing

Form-function relationships are foundational to evolutionary biology, but we are only beginning to understand the mechanisms that link biomechanical function to morphological evolution. In bird wings, the pace of morphological evolution follows a gradient of aerodynamic force production along the wing, with the fastest rates experienced at the wingtip. We examined how this gradient has manifested in the evolution of the individual flight feathers that comprise the wing surface. Specifically, we studied whether the flight feathers show a pattern of allometric scaling with respect to avian body size, and if the allometric pattern varies along the wing. We also asked whether the pace of evolution of the primary flight feathers follows the same gradient pattern as the overall wing morphology, and if there is modularity within the feather series. We measured the lengths of each of the primary flight feathers from 509 wings representing 514 bird species and calculated morphological disparity and evolutionary rate for each feather in the primary sequence. We found that evolutionary rate and disparity increase significantly toward the wingtip. We also found evidence for modularity within the feather sequence, but we were unable to positively delineate those modules. Our study provides further evidence that the mechanical sensitivity of morphological traits predicts their evolution, with highly sensitive features biased toward higher rates, and that it scales across multiple levels of anatomical organization.

evolutionary biology↗

bioRxiv2024

Mitomycin C Retains Efficacy after Adaptive Laboratory Evolution of Staphylococcus aureus

Antibiotic resistance is one of the greatest threats against human health and the misuse and overuse of antibiotics is a key factor driving resistance development. During prolonged antibiotic treatment of chronic infections, the antimicrobial pressure facilitates selection of antibiotic resistance mutations. It has been suggested that using antibiotics in combinations may reduce the emergence of resistance. Furthermore, antibiotic tolerant persister cells may be a reservoir for resistance development, so targeting persister cells with anti-persister drugs could also reduce the emergence of resistance. In this study, we conducted a 42-day adaptive laboratory evolution experiment using Staphylococcus aureus exposed to common antibiotics and the anti-persister drug mitomycin C, either alone or in combination. We monitored susceptibility daily and assessed phenotypic changes in growth and biofilm formation in evolved strains. Whole-genome sequencing revealed mutations linked to antibiotic resistance and phenotypic shifts. Resistance developed rapidly against rifampicin, while ciprofloxacin and daptomycin showed slower resistance emergence. Treatments with vancomycin or mitomycin C resulted in minimal changes in susceptibility. Combination therapies generally delayed resistance, though resistance was not fully prevented. Notably, mitomycin C combined with rifampicin effectively suppressed rifampicin resistance. Sub-inhibitory antibiotic concentrations were associated with both known and novel mutations, including in the nucleotide excision repair system and azoreductase, following mitomycin C treatment--mutations not previously reported. While combination therapy delayed resistance, mitomycin Cs efficacy and ability to prevent rifampicin resistance highlights its potential in combating antibiotic resistance. Further investigation is needed to evaluate the broader application of anti-persister drugs in resistance prevention.

microbiology↗

bioRxiv2023

A novel high-throughput assay identifies small molecules with activity against persister cells

Persister cells are a subpopulation of transiently antibiotic tolerant bacteria, which are believed to be the main cause of relapsing bacterial infections. Due to the importance of persister cells in human infections, there is a need for new antibiotics that kill bacteria independently of their activity. However, high-throughput assays to screen for drugs with such activity are missing. This is partly due to the transient nature of the phenotype, which makes it is difficult to prepare a concentrated population of persister cells that remain inactive during incubation with antibiotics in standard growth media. The purpose of this study was to develop a simple and high-throughput assay to identify compounds with antimicrobial activity against persister cells during a 24 h incubation period. Subsequently, this assay was used to screen a selection of small molecules with hypothesized antimicrobial activity. The fraction of S. aureus that tolerate bactericidal concentrations of ciprofloxacin were defined as persister cells. We first quantified how the cell concentration, growth phase, antibiotic concentration, duration of antibiotic exposure, and presence/absence of nutrients during antibiotic exposure affected the fraction of persister cells in a population. After optimizing these parameters, we compared our approach to generate persister cells, to a process that generated persister cells by a short exposure to rifampicin. Finally, we used the optimised protocol to identify molecular structures that have anti-persister activity by performing screening on initially compound fragments and then selecting compounds that incorporated the fragments that displayed activity. We show that exponential- and stationary-phase cultures transferred to nutrient-rich media only contain a small fraction (0.001 to 0.07 %) of persister cells that tolerated 10, 50 and 100 x MIC ciprofloxacin. Exponential-phase cultures displayed a bi-phasic time-kill curve, which plateaued after 5 h exposure, while stationary phase cultures displayed a low, but constant death rate at 50 and 100 x MIC ciprofloxacin. Inducing the persister phenotype with a short rifampicin treatment resulted in 100% persister cells when evaluated after [≤]5 h exposure to ciprofloxacin. However, after longer incubation times, cells resumed activity and lost their tolerance to ciprofloxacin. Tolerance was only maintained in the majority of the population for the full 24 h incubation period if cells were transferred to a carbon-free minimal medium before exposure to ciprofloxacin. We conclude that keeping cells starved in a carbon-free medium enables generation of high concentrations of S. aureus cells that tolerate 50 x MIC ciprofloxacin, and we find this protocol easily applicable for rapid screening of anti-persister drugs that act on dormant or non-dividing cells.

microbiology↗

bioRxiv2023

Toxin/Antitoxin Systems Induce Persistence and Work in Concert with Restriction/Modification Systems to Inhibit Phage

Myriad bacterial anti-phage systems have been described and often the mechanism of programmed cell death is invoked for phage inhibition. However, there is little evidence of suicide under physiological conditions for these systems. Instead of death to stop phage propagation, we show here that persister cells, i.e., transiently-tolerant, dormant, antibiotic-insensitive cells, are formed and survive using the Escherichia coli C496_10 tripartite toxin/antitoxin system MqsR/MqsA/MqsC to inhibit T2 phage. Specifically, MqsR/MqsA/MqsC inhibited T2 phage by one million-fold and reduced T2 titers by 500-fold. During T2 phage attack, in the presence of MqsR/MqsA/MqsC, evidence of persistence include the single-cell physiological change of reduced metabolism (via flow cytometry), increased spherical morphology (via transmission electron microscopy), and heterogeneous resuscitation. Critically, we found restriction-modification systems (primarily EcoK McrBC) work in concert with the toxin/antitoxin system to inactivate phage, likely while the cells are in the persister state. Phage attack also induces persistence in Klebsiella and Pseudomonas spp. Hence, phage attack invokes a stress response similar to antibiotics, starvation, and oxidation, which leads to persistence, and this dormant state likely allows restriction/modification systems to clear phage DNA.

molecular biology↗