Macrocolony of NDM-1 Producing Enterobacter hormaechei subsp. oharae Generates Subpopulations with Different Features Regarding the Response of Antimicrobial Agents and Biofilm Formation

Pathogens

Danielle da Silva Trentin¹  FláviaRoberta Brust²  AlexandreJosé Macedo²  Luana Boff²  Franciele Pedrotti Rozales³  AfonsoLuís Barth³ 

[1] Basic Health Sciences Department, Federal University of Health Sciences of Porto Alegre, Porto Alegre, Rio Grande do Sul CE 90050-170, Brazil;Faculty of Pharmacy and Center of Biotechnology, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul CE 90610-000, Brazil;Laboratory of Research in Bacterial Resistance, Center for Experimental Research, Clinical Hospital of Porto Alegre, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul CE 90035-007, Brazil;

关键词: Enterobacter;    macrocolony biofilm;    bla_NDM-1;    antimicrobial treatment;    Galleria mellonella;   

DOI  :  10.3390/pathogens8020049

来源: DOAJ

【 摘 要 】

Enterobacter cloacae complex has been increasingly recognized as a nosocomial pathogen representing the third major Enterobacteriaceae species involved with infections. This study aims to evaluate virulence and antimicrobial susceptibility of subpopulations generated from macrocolonies of NDM-1 producing Enterobacter hormaechei clinical isolates. Biofilm was quantified using crystal violet method and fimbrial genes were investigated by PCR. Susceptibility of antimicrobials, alone and combined, was determined by minimum inhibitory concentration and checkerboard assays, respectively. Virulence and efficacy of antimicrobials were evaluated in Galleria mellonella larvae. Importantly, we verified that some subpopulations that originate from the same macrocolony present different biofilm production ability and distinct susceptibility to meropenem due to the loss of bla_NDM-1 encoding plasmid. A more in-depth study was performed with the 798 macrocolony subpopulations. Type 3 fimbriae were straightly related with biofilm production; however, virulence in larvae was not statistically different among subpopulations. Triple combination with meropenem–rifampicin–polymyxin B showed in vitro synergistic effect against all subpopulations; while in vivo this treatment showed different efficacy rates for 798-1S and 798-4S subpopulations. The ability of multidrug resistant E. hormaechei isolates in generating bacterial subpopulations presenting different susceptible and virulence mechanisms are worrisome and may explain why these infections are hardly overcome.

【 授权许可】

Unknown