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Published on: January 27, 2021
Increased ompW and ompA expression and higher virulence of Acinetobacter baumannii persister cells
Brenda Landvoigt Schmitt1,2, Bruna Ferreira Leal1, Mariana Leyser1,2
1Laboratório de Imunologia e Microbiologia, Escola de Ciências da Saúde e da Vida, Pontifícia Universidade Católica do Rio Grande do Sul, PUCRS, Porto Alegre, Brazil.
Background:
Acinetobacter baumannii is one of the main causes of healthcare-associated infections that threaten public health, and carbapenems, such as meropenem, have been a therapeutic option for these infections. Therapeutic failure is mainly due to the antimicrobial resistance of A. baumannii, as well as the presence of persister cells. Persisters constitute a fraction of the bacterial population that present a transient phenotype capable of tolerating supra-lethal concentrations of antibiotics. Some proteins have been suggested to be involved in the onset and/or maintenance of this phenotype. Thus, we investigated the mRNA levels of the adeB (AdeABC efflux pump component), ompA, and ompW (outer membrane proteins) in A. baumannii cells before and after exposure to meropenem.
Results:
We found a significant increase (p-value < 0.05) in the expression of ompA (> 5.5-fold) and ompW (> 10.5-fold) in persisters. However, adeB did not show significantly different expression levels when comparing treated and untreated cells. Therefore, we suggest that these outer membrane proteins, especially OmpW, could be part of the mechanism of A. baumannii persisters to deal with the presence of high doses of meropenem. We also observed in the Galleria mellonella larvae model that persister cells are more virulent than regular ones, as evidenced by their LD50 values.
Conclusions:
Taken together, these data contribute to the understanding of the phenotypic features of A. baumannii persisters and their relation to virulence, as well as highlight OmpW and OmpA as potential targets for drug development against A. baumannii persisters.
Insights
Acinetobacter baumannii persister cells, which tolerate antibiotics, show increased expression of outer membrane proteins OmpA and OmpW. These proteins, particularly OmpW, may help bacteria survive meropenem, and persisters are more virulent.
Area of Science:
- Microbiology
- Infectious Diseases
- Antimicrobial Resistance
Background:
- Acinetobacter baumannii is a major cause of healthcare-associated infections.
- Antimicrobial resistance and persister cells contribute to treatment failures.
- Persister cells are a subpopulation tolerant to antibiotics.
Purpose of the Study:
- Investigate the role of specific genes in A. baumannii persister cell formation.
- Examine the expression of adeB, ompA, and ompW in response to meropenem exposure.
Main Methods:
- Gene expression analysis (mRNA levels) of adeB, ompA, and ompW.
- Comparison of gene expression in A. baumannii before and after meropenem treatment.
- Virulence assessment using Galleria mellonella larvae model.
Main Results:
- Significant upregulation of ompA (>5.5-fold) and ompW (>10.5-fold) in persister cells.
- No significant change in adeB expression.
- Persister cells exhibited higher virulence in the Galleria mellonella model.
Conclusions:
- OmpW and OmpA are likely involved in the tolerance mechanism of A. baumannii persisters to meropenem.
- Increased outer membrane protein expression contributes to antibiotic tolerance.
- A. baumannii persister cells are more virulent, suggesting potential therapeutic targets.
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