Streling Ana Paula, Barbosa Paula P, Marcondes Marcelo F, Nicoletti Adriana G, Picão Renata C, Pinto Elisa C, Marques Elizabeth A, Oliveira Vitor, Gales Ana C
Universidade Federal de São Paulo-UNIFESP, Laboratório Alerta, Division of Infectious Diseases, Department of Internal Medicine. Escola Paulista de Medicina-EPM, São Paulo, Brazil.
Universidade Federal de São Paulo-UNIFESP, Laboratório Alerta, Division of Infectious Diseases, Department of Internal Medicine. Escola Paulista de Medicina-EPM, São Paulo, Brazil.
Diagn Microbiol Infect Dis. 2018 Oct;92(2):147-151. doi: 10.1016/j.diagmicrobio.2018.05.003. Epub 2018 May 12.
We evaluated the genetic environment of bla found in 2 carbapenem-resistant Serratia marcescens clinical isolates recovered from patients hospitalized at a tertiary hospital located in Rio de Janeiro, Brazil. We also compared the kinetics constants for GES-16 and GES-5 against several β-lactams. Both S. marcescens isolates showed identical PFGE pattern and carried the carbapenemase-encoding gene bla and the extended-spectrum β-lactamase encoding gene bla. The bla was inserted at the first position of a defective class 1 integron, composed by a fragmented integrase gene that lacked its attI1 recombination site, followed by dfr22, aac(6')-IIc, and aadA1 genes. This integron was located on a 30-kb nonconjugative plasmid. The GES-16 showed 2 amino acid substitutions (Gln38Glu and Gly170Ser) compared to GES-1. Kinetic analysis showed that GES-16 presented hydrolytic activity against all β-lactams tested, except for aztreonam. Imipenem was the carbapenem more efficiently hydrolyzed (highest k/K) by GES-16. The kinetic parameters of GES-16 were similar to those of GES-5. In conclusion, we identified a new GES-type enzyme with carbapenemase activity in S. marcescens. The increasing diversity of such resistance determinants confirms the ongoing evolution of these β-lactamases towards a broader spectrum of activity.
我们评估了从巴西里约热内卢一家三级医院住院患者中分离出的2株耐碳青霉烯类粘质沙雷氏菌临床分离株中bla的基因环境。我们还比较了GES-16和GES-5对几种β-内酰胺类抗生素的动力学常数。两株粘质沙雷氏菌分离株显示出相同的脉冲场凝胶电泳（PFGE）图谱，并携带碳青霉烯酶编码基因bla和超广谱β-内酰胺酶编码基因bla。bla插入到一个缺陷1类整合子的第一位，该整合子由一个缺少attI1重组位点的片段化整合酶基因组成，其后是dfr22、aac(6')-IIc和aadA1基因。这个整合子位于一个30 kb的非接合性质粒上。与GES-1相比，GES-16有2个氨基酸替换（Gln38Glu和Gly170Ser）。动力学分析表明，GES-16对除氨曲南外的所有测试β-内酰胺类抗生素均表现出水解活性。亚胺培南是GES-16水解效率最高（k/K最高）的碳青霉烯类抗生素。GES-16的动力学参数与GES-5相似。总之，我们在粘质沙雷氏菌中鉴定出一种具有碳青霉烯酶活性的新型GES型酶。此类耐药决定因素的多样性不断增加，证实了这些β-内酰胺酶正朝着更广泛的活性谱不断进化。
