Relationship Between Different Resistance Mechanisms and Virulence in Acinetobacter baumannii

Microb Drug Resist. 2019 Jun;25(5):752-760. doi: 10.1089/mdr.2018.0182. Epub 2019 Jan 11.

Abstract

Aim: This study analyzed the virulence of several Acinetobacter baumannii strains expressing different resistance mechanisms using the Caenorhabditis elegans infection model. Results: Strains susceptible/resistant to carbapenems (presenting class D (OXA-23, OXA-24), class B metallo-β-lactamase (MBL) (NDM-1), penicillin binding protein (PBP) altered and decreased expression of Omp 33-36 kDa) and isogenic A. baumannii strains susceptible/resistant to colistin (presenting loss of lipopolysaccharide (LPS) and pmrA mutations) were included to evaluate the virulence using the C. elegans infection model. The nematode killing assay, bacterial ingestion in worms, and bacterial lawn avoidance assay were performed with the Fer-15 mutant line. A. baumannii strains generally presented low virulence, showing no difference between carbapenem-resistant strains (expressing class D, MBLs, or altered PBP) and their isogenic susceptible strains. In contrast, the absence of the Omp 33-36 kDa protein in the knockout was associated with a decrease of virulence, and a significant difference was observed between colistin-resistant mutants and their susceptible counterpart when the mechanism of resistance was associated with the loss of LPS but not with its modification. Conclusions: Resistance to carbapenems in A. baumannii associated with the production of OXA-type or NDM-type enzymes does not seem to affect their virulence in the C. elegans infection model. In contrast, the presence of Omp 33-36 kDa, and high level resistance to colistin related with the loss of LPS, might contribute with the virulence profile in A. baumannii.

Keywords: carbapenemase; impermeability; multidrug resistance; virulence.

MeSH terms

  • Acinetobacter Infections / drug therapy
  • Acinetobacter Infections / microbiology
  • Acinetobacter baumannii / drug effects
  • Acinetobacter baumannii / genetics*
  • Acinetobacter baumannii / pathogenicity*
  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Proteins / genetics
  • Caenorhabditis elegans / microbiology*
  • Carbapenems / pharmacology
  • Colistin / pharmacology
  • DNA Gyrase / genetics
  • DNA Topoisomerase IV / genetics
  • Disease Models, Animal
  • Drug Resistance, Multiple, Bacterial / genetics*
  • Gene Expression
  • Humans
  • Lipopolysaccharides / deficiency*
  • Longevity / genetics
  • Microbial Sensitivity Tests
  • Mutation
  • Penicillin-Binding Proteins / genetics
  • Serogroup
  • Virulence
  • beta-Lactamases / genetics

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Carbapenems
  • Lipopolysaccharides
  • Penicillin-Binding Proteins
  • pmrA protein, Bacteria
  • beta-lactamase OXA-23
  • beta-Lactamases
  • beta-lactamase OXA-24
  • DNA Topoisomerase IV
  • DNA Gyrase
  • Colistin