López Lázaro, Calderón Diana, Salinas Liseth, Graham Jay P, Blount Zachary D, Trueba Gabriel
Instituto de Microbiologa, Colegio de Ciencias Biolgicas y Ambientales, Universidad San Francisco de Quito, Quito, Ecuador.
Laboratorio de Biotecnologa de Plantas, Universidad San Francisco de Quito, Quito, Ecuador.
Microbiology (Reading). 2025 Jan;171(1). doi: 10.1099/mic.0.001525.
Antimicrobial resistance (AMR) is a major threat to global public health that continues to grow owing to selective pressure caused by the use and overuse of antimicrobial drugs. Resistance spread by plasmids is of special concern, as they can mediate a wide distribution of AMR genes, including those encoding extended-spectrum -lactamases (ESBLs). The CTX-M family of ESBLs has rapidly spread worldwide, playing a large role in the declining effectiveness of third-generation cephalosporins. This rapid spread across the planet is puzzling given that plasmids carrying AMR genes have been hypothesized to incur a fitness cost to their hosts in the absence of antibiotics. Here, we focus on a WT plasmid that carries the ESBL gene. We examine its conjugation rates and use head-to-head competitions to assay its associated fitness costs in both laboratory and wild strains. We found that the wild strains exhibit intermediate conjugation levels, falling between two high-conjugation and two low-conjugation laboratory strains, the latter being older and more ancestral. We also show that the plasmid increases the fitness of both WT and lab strains when grown in lysogeny broth and Davis-Mingioli media without antibiotics, which might stem from metabolic benefits conferred on the host, or from interactions between the host and the rifampicin-resistant mutation we used as a selective marker. Laboratory strains displayed higher conjugation frequencies compared to WT strains. The exception was a low-passage K-12 strain, suggesting that prolonged laboratory cultivation may have compromised bacterial defences against plasmids. Despite low transfer rates among WT , the plasmid carried low fitness cost in minimal medium but conferred improved fitness in enriched medium, indicating a complex interplay between plasmids, host genetics and environmental conditions. Our findings reveal an intricate relationship between plasmid carriage and bacterial fitness. Moreover, they show that resistance plasmids can confer adaptive advantages to their hosts beyond AMR. Altogether, these results highlight that a closer study of plasmid dynamics is critical for developing a secure understanding of how they evolve and affect bacterial adaptability that is necessary for combating resistance spread.
抗菌药物耐药性（AMR）是对全球公共卫生的重大威胁，由于抗菌药物的使用和过度使用所造成的选择压力，这种威胁还在持续加剧。由质粒传播的耐药性尤其令人担忧，因为它们可以介导AMR基因的广泛传播，包括那些编码超广谱β-内酰胺酶（ESBLs）的基因。CTX-M家族的ESBLs已在全球迅速传播，在第三代头孢菌素疗效下降中起了很大作用。考虑到携带AMR基因的质粒在没有抗生素的情况下被认为会给宿主带来适应性代价，这种在全球范围内的迅速传播令人费解。在这里，我们聚焦于一个携带ESBL基因的野生型质粒。我们检测了它的接合率，并通过直接竞争实验来测定其在实验室菌株和野生菌株中的相关适应性代价。我们发现野生菌株表现出中等接合水平，介于两个高接合水平和两个低接合水平的实验室菌株之间，后两者更为古老且更接近祖先菌株。我们还表明，当在无抗生素的溶原肉汤和戴维斯-明乔利培养基中生长时，该质粒提高了野生型和实验室菌株的适应性，这可能源于赋予宿主的代谢益处，或者源于宿主与我们用作选择标记的耐利福平突变之间的相互作用。与野生型菌株相比，实验室菌株表现出更高的接合频率。唯一的例外是低传代的K-12菌株，这表明长时间的实验室培养可能削弱了细菌对质粒的防御能力。尽管野生型菌株之间的转移率较低，但该质粒在基本培养基中携带的适应性代价较低，而在富集培养基中则赋予更好的适应性，这表明质粒、宿主遗传学和环境条件之间存在复杂的相互作用。我们的研究结果揭示了质粒携带与细菌适应性之间的复杂关系。此外，它们表明耐药质粒除了AMR之外，还可以赋予宿主适应性优势。总之，这些结果突出表明，更深入地研究质粒动态对于安全理解它们如何进化以及如何影响细菌适应性（这对于对抗耐药性传播至关重要）至关重要。
