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Increased ompW and ompA expression and higher virulence of Acinetobacter baumannii persister cells

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Abstract 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.
Title: Increased ompW and ompA expression and higher virulence of Acinetobacter baumannii persister cells
Description:
Abstract 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.

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