NiPharmins: novel low resistance-inducing antimicrobials with antibiofilm activity against Staphylococcus aureus

João P. Carrilho, Nuno R. Candeias, Alexandra Nunes

Research output: Contribution to conferenceAbstractpeer-review

Abstract

The rapid increase of Staphylococcus aureus antimicrobial resistance (AMR) together with their
impact in healthcare highlights the urgent need of alternative therapeutic compounds. We have
recently demonstrated that novel alkylaminophenols (NiPharmins) are promising effective
antibacterial agents against S. aureus, evidencing a very low potential of inducing AMR. Herein,
we intend to get a step further in NiPharmins’ validation as a promising prophylactic option against
S. aureus infections by evaluating its antibiofilm activity. S. aureus (SA-1) isogenic clones were
continuously propagated in vitro without and under sub-MIC of one of the most potent NiPharmins
(Nph1). Phenotypic tests coupled with WGS were used to assess the putative AMR acquisition by
expressing staphylococcal biofilm. The impact of Nhp1 prolonged exposure at sub-MIC conditions
on bacterial susceptibility against a panel of 16 antibiotics was also evaluated. Moreover, the
capacity of NiPharmins for inhibiting biofilms from the staphylococcal populations evolved under
selective pressure was studied. Overall, the biofilm expression of SA-1 lead to AMR, with all
staphylococcal populations growing to at least 4xMIC. Furthermore, for each antibiotic tested, no
significant differences in antimicrobial susceptibility were seen among all bacterial populations
(wild-type, positive control, and Nph1-evolved populations), suggesting that prolonged exposure to
Nph1 sub-MIC does not adversely affect the bacterial original AMR profile to traditional antibiotics.
This compound also demonstrated great efficiency in inhibiting the formation of biofilms, at MIC
concentration, of all SA-1 populations. Genomic analyses revealed nonsynonymous mutations on
important transcriptional regulators, namely AraC and AcrR, both related to biofilm formation.
Mutations in Pur operon repressor (PurR), also related with the expression of biofilms, was likewise
observed. This work reinforces the potential of these novel antibacterial compounds as promising
prophylactic alternatives for the prevention of S. aureus infections.
Original languageEnglish
Publication statusPublished - Dec 2023
EventCongress of Microbiology and Biotechnology 2023 - Covilhã, Portugal
Duration: 7 Dec 20239 Dec 2023

Conference

ConferenceCongress of Microbiology and Biotechnology 2023
Country/TerritoryPortugal
CityCovilhã
Period7/12/239/12/23

Keywords

  • Antimicrobial resistance
  • Biofilms

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