New insights about the EptA protein and its correlation with the pmrC gene in polymyxin resistance in Pseudomonas aeruginosa

Freire, Cindy Magda Araújo dos Santos; Taunay-Rodrigues, Alessandro; Gonzatti, Michelangelo Bauwelz; Fonseca, Fátima Morgana Pio; Freire, José Ednésio da Cruz

doi:10.1016/j.crmicr.2021.100042

Cited by 1 publication

(1 citation statement)

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“…In addition, in another work analyzing the collateral effects of resistant mutants obtained in a morbidostat device, although an increased serum resistance and biofilm formation capacity appeared in parallel to colistin resistance, virulence attenuation in G. mellonella model was also seen after 21 days of exposure to the drug, once more evidencing the intricate nature of resistance vs. fitness/virulence interplay ( Dößelmann et al, 2017 ; Javed et al, 2021 ). Finally, another less known potential colistin resistance mechanism, namely the addition of phosphoethanolamine to lipid A through the chromosomal enzyme EptA ( Nowicki et al, 2015 ; Freire et al, 2021 ), has also been approached regarding its potentially associated burden. In this sense, EptA hyperexpression has been shown to cause growth, competitiveness, and cell envelope defects that were not linked to phosphoethanolamine transferase activity per se ( Cervoni et al, 2023 ).…”

Section: Mutation-driven Resistancementioning

confidence: 99%

The balance between antibiotic resistance and fitness/virulence in Pseudomonas aeruginosa: an update on basic knowledge and fundamental research

Jordana-Lluch,

Barceló,

Escobar-Salom

et al. 2023

Front. Microbiol.

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The interplay between antibiotic resistance and bacterial fitness/virulence has attracted the interest of researchers for decades because of its therapeutic implications, since it is classically assumed that resistance usually entails certain biological costs. Reviews on this topic revise the published data from a general point of view, including studies based on clinical strains or in vitro-evolved mutants in which the resistance phenotype is seen as a final outcome, i.e., a combination of mechanisms. However, a review analyzing the resistance/fitness balance from the basic research perspective, compiling studies in which the different resistance pathways and respective biological costs are individually approached, was missing. Here we cover this gap, specifically focusing on Pseudomonas aeruginosa, a pathogen that stands out because of its extraordinary capacity for resistance development and for which a considerable number of recent and particular data on the interplay with fitness/virulence have been released. The revised information, split into horizontally-acquired vs. mutation-driven resistance, suggests a great complexity and even controversy in the resistance-fitness/virulence balance in the acute infection context, with results ranging from high costs linked to certain pathways to others that are seemingly cost-free or even cases of resistance mechanisms contributing to increased pathogenic capacities. The elusive mechanistic basis for some enigmatic data, knowledge gaps, and possibilities for therapeutic exploitation are discussed. The information gathered suggests that resistance-fitness/virulence interplay may be a source of potential antipseudomonal targets and thus, this review poses the elementary first step for the future development of these strategies harnessing certain resistance-associated biological burdens.

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