Pimentel Camila, Le Casin, Tuttobene Marisel R, Subils Tomas, Papp-Wallace Krisztina M, Bonomo Robert A, Tolmasky Marcelo E, Ramirez Maria Soledad
Center for Applied Biotechnology Studies, Department of Biological Science, College of Natural Sciences and Mathematics, California State University Fullerton, Fullerton, CA 92831-3599, USA.
Área Biología Molecular, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Rosario 2000, Argentina.
Antibiotics (Basel). 2021 Jul 8;10(7):833. doi: 10.3390/antibiotics10070833.
has become a serious threat to human health due to its extreme antibiotic resistance, environmental persistence, and capacity to survive within the host. Two strains, A118 and AB5075, commonly used as model systems, and three carbapenem-resistant strains, which are becoming ever more dangerous due to the multiple drugs they can resist, were exposed to 3.5% human serum albumin (HSA) and human serum (HS) to evaluate their response with respect to antimicrobial resistance, biofilm formation, and quorum sensing, all features responsible for increasing survival and persistence in the environment and human body. Expression levels of antibiotic resistance genes were modified differently when examined in different strains. The gene was upregulated or downregulated in conditions of exposure to 3.5% HSA or HS depending on the strain. Expression levels of and tended to be increased by the presence of HSA and HS, but the effect was not seen in all strains. A118 growing in the presence of HS did not experience increased expression of these genes. Aminoglycoside-modifying enzymes were also expressed at higher or lower levels in the presence of HSA or HS. Still, the response was not uniform; in some cases, expression was enhanced, and in other cases, it was tapered. While AB5075 became more susceptible to rifampicin in the presence of 3.5% HSA or HS, strain A118 did not show any changes. Expression of a gene involved in resistance to rifampicin present in AMA16, was expressed at higher levels when HS was present in the culture medium. HSA and HS reduced biofilm formation and production of N-Acyl Homoserine Lactone, a compound intimately associated with quorum sensing. In conclusion, HSA, the main component of HS, stimulates a variety of adaptative responses in infecting strains.
由于其极强的抗生素耐药性、环境持久性以及在宿主体内生存的能力，已对人类健康构成严重威胁。常用作模型系统的两株菌A118和AB5075，以及三株耐碳青霉烯类菌株（因其能抵抗多种药物而变得愈发危险），被暴露于3.5%的人血清白蛋白（HSA）和人血清（HS）中，以评估它们在抗菌耐药性、生物膜形成和群体感应方面的反应，这些特性都有助于在环境和人体中提高生存能力和持久性。在不同菌株中检测时，抗生素耐药基因的表达水平变化各异。根据菌株不同，该基因在暴露于3.5% HSA或HS的条件下会上调或下调。 和 的表达水平往往会因HSA和HS的存在而升高，但并非在所有菌株中都如此。在HS存在的情况下生长的A118并未出现这些基因表达增加的情况。氨基糖苷修饰酶在HSA或HS存在时也会有较高或较低水平的表达。不过，反应并不一致；在某些情况下，表达增强，而在其他情况下则减弱。虽然AB5075在3.5% HSA或HS存在时对利福平变得更敏感，但A118菌株未显示任何变化。AMA16中存在的与利福平耐药相关的一个基因，当培养基中存在HS时表达水平更高。HSA和HS减少了生物膜形成以及N-酰基高丝氨酸内酯的产生，N-酰基高丝氨酸内酯是一种与群体感应密切相关的化合物。总之，HS的主要成分HSA会刺激感染菌株产生多种适应性反应。
