AbstractIn many bacteria, protein mass production is thought to be rate limiting for growth, implying exponential growth at the single cell level. To maintain cell-size homeostasis in proliferating populations of exponentially growing bacteria, tight growth and division mechanisms are required. However, it remains unclear whether these considerations set universal physical limits to bacterial growth. Here, we characterize the growth dynamics of the actinobacterium Corynebacterium glutamicum - a promising candidate for uncovering novel growth modes. This bacterium exhibits apical cell wall synthesis and division site selection systems appear to be absent, as reflected by a broad distribution of division asymmetries. We develop a novel growth inference method that averages out measurement noise and single-cell variability to obtain elongation rate curves as a function of birth length. Using this approach, we find that C. glutamicum exhibits asymptotically linear single-cell growth. To explain this growth mode, we model elongation as being rate-limited by the apical growth mechanism mediated by cell wall transglycosylases. This model accurately reproduces the observed elongation rate curves, and we further validate the model with growth measurements on a transglycosylase deficient ΔrodA mutant. Finally, with simulations we show that asymptotically linear growth yields a narrower distribution of cell lengths, suggesting that this growth mode can act as a substitute for tight division length and division symmetry regulation.SignificanceRegulation of growth and cell size is crucial for the optimization of bacterial cellular function. So far, single bacterial cells have been found to grow exponentially, which implies the need for tight regulation mechanisms to maintain cell size throughout growth and division cycles. Here, we characterize the growth behavior of the apically growing bacterium Corynebacterium glutamicum, by developing a novel and broadly applicable inference method for single-cell growth dynamics. We find that this bacterium grows asymptotically linearly, enabling it to maintain a narrow distribution of cell sizes, despite having a large variability of single-cell growth features. Our results imply a novel interplay between mode of growth and division regulation mechanisms, which may extend to other bacteria with non-exponential growth modes.
Single-cell growth inference of Corynebacterium glutamicum reveals asymptotically linear growth
