Biology subjects

Micali, G.

Publications and source records attributed to Micali, G..

5 recordsLinked to original sources

bioRxiv2025

Phage-mediated lysis increases growth rate of surviving bacterial cells

Bacterial phage infection and subsequent lysis are traditionally considered mechanisms of bacterial mortality and viral propagation; additionally, emerging evidence indicates that they may also contribute to nutrient recycling in broader ecological systems. However, it remains unclear how the nutrients released during cell lysis affect the growth dynamics of the remaining bacterial population. Addressing this gap, we built a controlled system consisting of two Escherichia coli lysogenic strains: one carrying a wild-type{lambda} prophage and the other a temperature-inducible variant that can be induced to lyse at 38 {degrees}C. Using this system, we selectively induced phage lysis in a defined fraction of the population and quantified both total biomass and the biomass of surviving, non-lysed cells. We observed that the biomass loss was consistently smaller than expected based on the fraction of lysed cells, supporting the idea that some of the released biomass is rapidly recycled by the non-lysed population. To formalize the observed dynamics and obtain quantitative insight, we developed a mathematical model showing that nutrients released during lysis can transiently enhance the growth rate of the surviving, non-lysed cells. This effect emerges on a short timescale of minutes, consistent with the rapid onset of biomass compensation observed experimentally. The growth rate increase was confirmed in single-cell experiments using microfluidics and time-lapse microscopy, where we cultured wild-type lysogens in lysate-containing culture supernatants. In summary, the results suggest that nutrients released through lysis are rapidly consumed, leading to an acceleration in the growth rate of non-lysed cells. The consequent partial compensation for cell loss can substantially influence the population dynamics, highlighting phage lysis as a direct modulator of bacterial growth. Overall, our findings provide quantitative insights into how phage-mediated lysis affects the physiology of non-lysed bacterial cells, extending beyond its well-established role in biomass recycling.

microbiology↗

bioRxiv2021

Two different cell-cycle processes determine the timing of cell division in Escherichia coli

Cells must control the cell cycle to ensure that key processes are brought to completion. In Escherichia coli, it is controversial whether cell division is tied to chromosome replication or to a replication-independent inter-division process. A recent model suggests instead that both processes may limit cell division with comparable odds in single cells. Here, we tested this possibility experimentally by monitoring single-cell division and replication over multiple generations at slow growth. We then perturbed cell width, causing an increase of the time between replication termination and division. As a consequence, replication became decreasingly limiting for cell division, while correlations between birth and division and between subsequent replication-initiation events were maintained. Our experiments support the hypothesis that both chromosome replication and a replication-independent inter-division process can limit cell division: the two processes have balanced contributions in non-perturbed cells, while our width perturbations increase the odds of the replication-independent process being limiting.

systems biology↗

bioRxiv2021

Microbiota-derived metabolites inhibit Salmonella virulent subpopulation development by acting on single-cell behaviors

Salmonella spp. express Salmonella pathogenicity island 1 (SPI-1) genes to mediate the initial phase of interaction with host cells. Prior studies indicate short-chain fatty acids, microbial metabolites at high concentrations in the gastrointestinal tract, limit SPI-1 gene expression. A number of reports show only a subset of Salmonella cells in a population express these genes, suggesting short-chain fatty acids could decrease SPI-1 population-level expression by acting on per-cell expression and/or the proportion of expressing cells. Here, we combine single-cell, theoretical, and molecular approaches to address the effect of short-chain fatty acids on SPI-1 expression. Our results show short-chain fatty acids do not repress SPI-1 expression by individual cells. Rather, these compounds act to selectively slow the growth of SPI-1 expressing cells, ultimately decreasing their frequency in the population. Further experiments indicate slowed growth arises from short-chain fatty acid-mediated depletion of the proton motive force. By influencing the SPI-1 cell-type proportions, our findings imply gut microbial metabolites act on cooperation between the two cell-types and ultimately influence Salmonellas capacity to establish within a host. Significance StatementEmergence of distinct cell-types in populations of genetically identical bacteria is common. Furthermore, it is becoming increasingly clear that cooperation between cell-types can be beneficial. This is the case during Salmonella infection, in which cooperation between inflammation-inducing virulent and fast-growing avirulent cell-types occurs during infection to aid in colonization of the host gut. Here, we show gut microbiota-derived metabolites slow growth by the virulent cell-type. Our study implies microbial metabolites shape cooperative interactions between the virulent and avirulent cell types, a finding that can help explain the wide array of clinical manifestations of Salmonella infection.

microbiology↗

bioRxiv2018

Dissecting the control mechanisms for DNA replication and cell division in E. coli

Understanding how single E. coli cells coordinate the timing of cell division with genome replication would unlock a classic problem of biology, and open the way to address cell-cycle progression at the single-cell level. Several recent studies produced new data and proposed different models, based on the hypothesis that replication-segregation is the bottleneck process for cell division. However, due to the apparent contrast in both experimental results and proposed mechanisms, the emerging picture is fragmented and unclear. In this work, we re-evaluate jointly available data and models, and we show that, while each model contains useful insights, none of the proposed models, as well as generalizations based on the same assumptions, correctly describes all the correlation patterns observed in data. This analysis leads us to conclude that the assumption that replication is the bottleneck process for cell division is too restrictive. Instead, we propose that two concurrent cycles responsible for division and initiation of DNA replication together set the time of cell division. This framework correctly captures available data and allows us to select a nearly constant added size per origin between subsequent initiations as the most likely mechanism setting initiation of replication.

cell biology↗

bioRxiv2018

Concurrent processes set E. coli cell division

A cell can divide only upon completion of chromosome segregation, or its daughters would lose genetic material [1, 2]. In E. coli bacteria, the prevalent view is that cells divide a fixed amount of time after they start to copy the chromosomes [3, 4], and a known pathway prevents cells from dividing if the chromosomes interfere with the cytokinesis machinery [5]. However, whether completion of segregation is typically the bottleneck process for the decision to divide has never been stringently tested on single cells. We show how key trends in single-cell data lead to challenge the classic idea of replication-segregation limiting cell division. Instead, the data agree with a model where two concurrent processes (setting replication initiation and inter-division time) set cell division on competing time scales. During each cell cycle, division is set by the slowest process (an \" ...

cell biology↗