Svet Luka, Parijs Ilse, Isphording Simon, Lories Bram, Marchal Kathleen, Steenackers Hans P
Department of Microbial and Molecular Systems, Centre of Microbial and Plant Genetics (CMPG), Leuven, Belgium.
Department of Plant Biotechnology and Bioinformatics, Data Integration and Biological Networks, UGent, Technologiepark 15, Gent, Belgium.
Appl Environ Microbiol. 2023 Oct 31;89(10):e0115523. doi: 10.1128/aem.01155-23. Epub 2023 Oct 11.
While the evolution of antimicrobial resistance is well studied in free-living bacteria, information on resistance development in dense and diverse biofilm communities is largely lacking. Therefore, we explored how the social interactions in a duo-species biofilm composed of the brewery isolates and influence the adaptation to the broad-spectrum antimicrobial sulfathiazole. Previously, we showed that the competition between these brewery isolates enhances the antimicrobial tolerance of . Here, we found that this enhanced tolerance in duo-species biofilms is associated with a strongly increased antimicrobial resistance development in . Whereas was not able to evolve resistance against sulfathiazole in monospecies conditions, it rapidly evolved resistance in the majority of the duo-species communities. Although the initial presence of was thus required for to acquire resistance, the resistance mechanisms did not depend on the presence of . Whole genome sequencing of resistant clones showed no clear mutational hot spots. This indicates that the acquired resistance phenotype depends on complex interactions between low-frequency mutations in the genetic background of the strains. We hypothesize that the increased tolerance in duo-species conditions promotes resistance by enhancing the selection of partially resistant mutants and opening up novel evolutionary trajectories that enable such genetic interactions. This hypothesis is reinforced by experimentally excluding potential effects of increased initial population size, enhanced mutation rate, and horizontal gene transfer. Altogether, our observations suggest that the community mode of life and the social interactions therein strongly affect the accessible evolutionary pathways toward antimicrobial resistance.IMPORTANCEAntimicrobial resistance is one of the most studied bacterial properties due to its enormous clinical and industrial relevance; however, most research focuses on resistance development of a single species in isolation. In the present study, we showed that resistance evolution of brewery isolates can differ greatly between single- and mixed-species conditions. Specifically, we observed that the development of antimicrobial resistance in certain species can be significantly enhanced in co-culture as compared to the single-species conditions. Overall, the current study emphasizes the need of considering the within bacterial interactions in microbial communities when evaluating antimicrobial treatments and resistance evolution.
虽然在自由生活的细菌中对抗菌药物耐药性的演变已有充分研究,但关于密集且多样的生物膜群落中耐药性发展的信息却极为匮乏。因此,我们探究了由啤酒厂分离株 和 组成的双物种生物膜中的社会相互作用如何影响对广谱抗菌药物磺胺噻唑的适应性。此前,我们表明这些啤酒厂分离株之间的竞争增强了 的抗菌耐受性。在此,我们发现双物种生物膜中这种增强的耐受性与 中抗菌药物耐药性的大幅增加有关。虽然 在单物种条件下无法进化出对磺胺噻唑的耐药性,但在大多数双物种群落中它迅速进化出了耐药性。因此,虽然 的初始存在是 获得耐药性所必需的,但耐药机制并不依赖于 的存在。对抗药的 克隆进行全基因组测序未发现明显的突变热点。这表明获得的耐药表型取决于菌株遗传背景中低频突变之间的复杂相互作用。我们推测,双物种条件下耐受性的增加通过增强对部分耐药突变体的选择以及开辟能够实现这种遗传相互作用的新进化轨迹来促进耐药性。通过实验排除初始种群规模增加、突变率提高和水平基因转移的潜在影响,这一假设得到了强化。总之,我们的观察结果表明,群落生活模式及其内部的社会相互作用强烈影响对抗菌药物耐药性的可及进化途径。
重要性
由于其巨大的临床和工业相关性,抗菌药物耐药性是研究最多的细菌特性之一;然而,大多数研究集中在单个物种孤立状态下的耐药性发展。在本研究中,我们表明啤酒厂分离株的耐药性进化在单物种和混合物种条件下可能有很大差异。具体而言,我们观察到与单物种条件相比,某些物种在共培养中抗菌药物耐药性的发展可显著增强。总体而言,当前研究强调在评估抗菌治疗和耐药性进化时需要考虑微生物群落中细菌内部的相互作用。