Guangdong Province Key Laboratory of Microbial Signals and Disease Control, Integrative Microbiology Research Centre, South China Agricultural Universitygrid.20561.30, Guangzhou, China.
Centre for New Antibacterial Strategies (CANS) & Research Group for Host-Microbe Interactions, Faculty of Health Sciences, The Arctic University of Norway, Tromsø, Norway.
mSystems. 2022 Aug 30;7(4):e0009222. doi: 10.1128/msystems.00092-22. Epub 2022 Jun 14.
Quorum sensing (QS) coordinates bacterial communication and cooperation essential for virulence and dominance in polymicrobial settings. QS also regulates the CRISPR-Cas system for targeted defense against parasitic genomes from phages and horizontal gene transfer. Although the QS and CRISPR-Cas systems are vital for bacterial survival, they undergo frequent selection in response to biotic and abiotic factors. Using the opportunistic Pseudomonas aeruginosa with well-established QS and CRISPR-Cas systems, we show how the social interactions between the acyl-homoserine lactone (AHL)-QS signal-blind mutants (Δ) and the CRISPR-Cas mutants are affected by phage exposure and nutrient availability. We demonstrate that media conditions and phage exposure alter the resistance and relative fitness of Δ and CRISPR-Cas mutants while tipping the fitness advantage in favor of the QS signal-blind mutants under nutrient-limiting conditions. We also show that the AHL signal-blind mutants are less selected by phages under QS-inducing conditions than the CRISPR-Cas mutants, whereas the mixed population of the CRISPR-Cas and AHL signal-blind mutants reduce phage infectivity, which can improve survival during phage exposure. Our data reveal that phage exposure and nutrient availability reshape the population dynamics between the Δ QS mutants and CRISPR-Cas mutants, with key indications for cooperation and conflict between the strains. The increase in antimicrobial resistance has created the need for alternative interventions such as phage therapy. However, as previously observed with antimicrobial resistance, phage therapy will not be effective if bacteria evolve resistance and persist in the presence of the phages. The QS is commonly known as an arsenal for bacteria communication, virulence, and regulation of the phage defense mechanism, the CRISPR-Cas system. The QS and CRISPR-Cas systems are widespread in bacteria. However, they are known to evolve rapidly under the influence of biotic and abiotic factors in the bacterial environment, resulting in alteration in bacterial genotypes, which enhance phage resistance and fitness. We believe that adequate knowledge of the influence of environmental factors on the bacterial community lifestyle and phage defense mechanisms driven by the QS and CRISPR-Cas system is necessary for developing effective phage therapy.
群体感应 (QS) 协调细菌通讯和合作，这对于多微生物环境中的毒力和优势至关重要。QS 还调节 CRISPR-Cas 系统，以针对噬菌体和水平基因转移的寄生基因组进行靶向防御。尽管 QS 和 CRISPR-Cas 系统对细菌的生存至关重要，但它们会经常受到生物和非生物因素的选择。我们利用具有成熟 QS 和 CRISPR-Cas 系统的机会性病原体铜绿假单胞菌，展示了酰基高丝氨酸内酯 (AHL)-QS 信号盲突变体 (Δ) 和 CRISPR-Cas 突变体之间的社会相互作用如何受到噬菌体暴露和营养可用性的影响。我们证明，培养基条件和噬菌体暴露会改变 Δ 和 CRISPR-Cas 突变体的抗性和相对适应性，而在营养有限的条件下，有利于 QS 信号盲突变体的适应性优势。我们还表明，在 QS 诱导条件下，与 CRISPR-Cas 突变体相比，AHL 信号盲突变体受噬菌体选择的程度较低，而 CRISPR-Cas 和 AHL 信号盲突变体的混合群体可降低噬菌体的感染力，从而在噬菌体暴露期间提高生存能力。我们的数据揭示了噬菌体暴露和营养可用性重塑了 Δ QS 突变体和 CRISPR-Cas 突变体之间的种群动态，这为菌株之间的合作和冲突提供了关键指示。抗菌药物耐药性的增加要求采用替代干预措施，如噬菌体治疗。然而，正如之前观察到的抗菌药物耐药性一样，如果细菌产生耐药性并在噬菌体存在的情况下持续存在，噬菌体治疗将不会有效。QS 通常被认为是细菌通讯、毒力和噬菌体防御机制 CRISPR-Cas 系统调节的武器库。QS 和 CRISPR-Cas 系统在细菌中广泛存在。然而，已知它们在细菌环境中的生物和非生物因素的影响下会迅速进化，导致细菌基因型的改变，从而增强噬菌体的抗性和适应性。我们相信，充分了解环境因素对由 QS 和 CRISPR-Cas 系统驱动的细菌群落生活方式和噬菌体防御机制的影响，对于开发有效的噬菌体治疗方法是必要的。
