Department of Biology, University of Oxford, Oxford, United Kingdom.
Department of Biochemistry, University of Oxford, Oxford, United Kingdom.
ISME J. 2024 Jan 8;18(1). doi: 10.1093/ismejo/wrae141.
Many bacteria kill competitors using short-range weapons, such as the Type VI secretion system and contact dependent inhibition (CDI). Although these weapons can deliver powerful toxins, they rely on direct contact between attacker and target cells. We hypothesized that movement enables attackers to contact more targets and thus greatly empower their weapons. To explore this, we developed individual-based and continuum models of contact-dependent combat which show that motility greatly improves toxin delivery through two underlying processes. First, genotypic mixing increases the inter-strain contact probability of attacker and sensitive cells. Second, target switching ensures attackers constantly attack new cells, instead of repeatedly hitting the same cell. We test our predictions with the pathogen Pseudomonas aeruginosa, using genetically engineered strains to study the interaction between CDI and twitching motility. As predicted, we find that motility works synergistically with CDI, in some cases increasing weapon efficacy up to 10,000-fold compared with non-motile scenarios. Moreover, we demonstrate that both mixing processes occur using timelapse single-cell microscopy and quantify their relative importance by combining experimental data with our model. Our work shows how bacteria can combine cell movement with contact-based weapons to launch powerful attacks on their competitors.
许多细菌使用短程武器(如 VI 型分泌系统和接触依赖抑制(CDI))来杀死竞争者。虽然这些武器可以输送强大的毒素,但它们依赖于攻击者和目标细胞之间的直接接触。我们假设运动可以使攻击者接触到更多的目标,从而大大增强他们的武器。为了探索这一点,我们开发了基于个体和连续模型的接触依赖性战斗模型,这些模型表明,运动通过两种潜在的过程极大地提高了毒素的输送效率。首先,基因型混合增加了攻击者和敏感细胞之间的菌株间接触概率。其次,目标切换确保攻击者不断攻击新的细胞,而不是反复攻击同一个细胞。我们使用经过基因工程改造的菌株来研究 CDI 和翻滚运动之间的相互作用,以此来验证我们的预测。正如预测的那样,我们发现运动与 CDI 具有协同作用,在某些情况下,与非运动情况下相比,武器的效力增加了 10000 倍。此外,我们通过延时单细胞显微镜证明了这两种混合过程的发生,并通过将实验数据与我们的模型相结合,量化了它们的相对重要性。我们的工作表明,细菌如何将细胞运动与基于接触的武器相结合,对其竞争者发动强大的攻击。