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铜绿假单胞菌的抗生素耐药性。

Antibiotic Resistance in Pseudomonas.

机构信息

Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Madrid, Spain.

出版信息

Adv Exp Med Biol. 2022;1386:117-143. doi: 10.1007/978-3-031-08491-1_5.

Abstract

Pseudomonas is a bacterial genus, with a bona fide environmental habitat that comprises different species, some of them causing diseases in humans and plants, as well as some strains with biotechnological potential. Amongst them, Pseudomonas aeruginosa is currently one of the most important nosocomial pathogens. In addition, this microorganism is a prevalent cause of chronic infections in cystic fibrosis patients and in people suffering from chronic obstructive pulmonary disease. The success of P. aeruginosa in colonising different habitats largely relies on its metabolic versatility and robustness. Besides, this bacterial pathogen harbours in its core genome a large set of virulence determinants that allows it to colonise/infect a variety of hosts, from unicellular organisms to humans. Nevertheless, these are not just the only conditions needed for infecting patients at hospitals. Taking into consideration that infected patients are regularly under antibiotic treatment, the ability to avoid antibiotics' action is also needed. In this sense, P. aeruginosa displays a characteristic low susceptibility to several antibiotics currently used in therapy. This is due to the reduced permeability of its cellular envelopes and the presence in its genome of an arrangement of genes encoding multidrug efflux pumps and antibiotic-inactivating enzymes that contribute to its resilience to antibiotics. Besides intrinsic resistance, P. aeruginosa is able to evolve towards antibiotic resistance through mutations (particularly relevant in the case of chronic infections) and via acquisition of antibiotic resistance genes. It is worth mentioning that acquired resistance is not the only venue that P. aeruginosa has for avoiding the action of antibiotics. Transient resistance can also confer this phenotype. Indeed, the induction of the expression of intrinsic resistance genes by conditions or compounds that P. aeruginosa could face during infection can compromise the effectiveness of antibiotics for treating such infections. In addition, tolerant cells able to survive during the exposure to bactericidal antibiotics without an increase in their antibiotic resistance phenotype are found as well in these patients, and they are the prelude of the evolution towards antibiotic resistance. Finally, P. aeruginosa biofilms, frequently encountered in the lungs of cystic fibrosis patients, in prostheses, or in catheters, present low antibiotic susceptibility and are associated with recalcitrance and disease worsening.

摘要

铜绿假单胞菌是一种细菌属,具有真实的环境栖息地,其中包含不同的物种,有些会导致人类和植物患病,还有一些菌株具有生物技术潜力。其中,铜绿假单胞菌是目前最重要的医院获得性病原体之一。此外,这种微生物是囊性纤维化患者和慢性阻塞性肺疾病患者慢性感染的常见原因。铜绿假单胞菌成功定植于不同栖息地在很大程度上依赖于其代谢的多功能性和稳健性。此外,这种细菌病原体的核心基因组中含有大量的毒力决定因素,使其能够定植/感染从单细胞生物到人类等各种宿主。然而,这些并不是感染医院患者所需的唯一条件。考虑到受感染的患者经常接受抗生素治疗,还需要能够避免抗生素的作用。从这个意义上说,铜绿假单胞菌对目前用于治疗的几种抗生素表现出特征性的低敏感性。这是由于其细胞包膜的通透性降低,以及其基因组中存在排列的编码多种药物外排泵和抗生素失活酶的基因,这有助于其对抗生素的耐药性。除了固有耐药性外,铜绿假单胞菌还能够通过突变(在慢性感染的情况下尤为重要)和获得抗生素耐药基因进化为抗生素耐药性。值得一提的是,获得性耐药并不是铜绿假单胞菌逃避抗生素作用的唯一途径。短暂耐药也可以赋予这种表型。事实上,铜绿假单胞菌在感染过程中可能遇到的条件或化合物诱导固有耐药基因的表达,会影响抗生素治疗此类感染的效果。此外,在暴露于杀菌抗生素时能够存活而其抗生素耐药表型没有增加的耐受细胞也存在于这些患者中,这是向抗生素耐药进化的前奏。最后,铜绿假单胞菌生物膜在囊性纤维化患者的肺部、假体或导管中经常被发现,其对抗生素的敏感性较低,并与难治性和疾病恶化有关。

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