Abstract
Staphylococcus aureus is one of the major causes of hospital- and community-associated bacterial infections throughout the world, which are difficult to treat due to the rising number of drug-resistant strains. New molecules displaying potent activity against this bacterium are urgently needed. In this study, d- and l-deoxynojirimycin (DNJ) and a small library of their N-alkyl derivatives were screened against S. aureus ATCC 29213, with the aim to identify novel candidates with inhibitory potential. Among them, N-nonyloxypentyl-l-DNJ (l-NPDNJ) proved to be the most active compound against S. aureus ATCC 29213 and its clinical isolates, with the minimum inhibitory concentration (MIC) value of 128 μg/mL. l-NPDNJ also displayed an additive effect with gentamicin and oxacillin against the gentamicin- and methicillin-resistant S. aureus isolate 00717. Sub-MIC values of l-NPDNJ affected S. aureus biofilm development in a dose-dependent manner, inducing a strong reduction in biofilm biomass. Moreover, real-time reverse transcriptase PCR analysis revealed that l-NPDNJ effectively inhibited at sub-MIC values the transcription of the spa, hla, hlb and sea virulence genes, as well as the agrA and saeR response regulator genes.
Highlights
Staphylococcus aureus is an important human pathogen responsible for a variety of communityand healthcare-associated infections [1,2], which are difficult to treat and to eradicate because of the acquisition of multiple antibiotic resistance [3] and biofilm growth of this organism on implantable medical devices [4]
The S. aureus hemolysins alpha-toxin (Hla), beta-toxin (Hlb) and phenol-soluble modulins (PSMs) all cause the lysis of eukaryotic cells [41,42] and may contribute to the formation of biofilms [5,43,44]
Our results showed that the treatment of S. aureus cells with l-NPDNJ decreased significantly the expression of the hla, hlb and sea genes (Figure 5)
Summary
Staphylococcus aureus is an important human pathogen responsible for a variety of communityand healthcare-associated infections [1,2], which are difficult to treat and to eradicate because of the acquisition of multiple antibiotic resistance [3] and biofilm growth of this organism on implantable medical devices [4]. A and Bulgecin held interesting inhibit Streptococcus mutans biofilm formation [24,25,26]. Other modified iminosugars such as properties against. An even more of the corresponding D‐iminosugars, showed higher selectivity towards specific enzymes interesting pharmacological potential towards several diseases than their d-enantiomers [20,21,32,33,34]. L-NBDNJ and its congeners as a promising selective new candidate fordisease the combination therapy of Pompe disease [34]. 2), the iminosugar enantiomer showing the derivatives (Figure 2) and the effects on the biofilm formation and virulence factors expression of S.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have