Inhibitory effects of antibiofilm compound 1 against <i>Staphylococcus aureus</i> biofilms

Shrestha, Looniva; Kayama, Shizuo; Sasaki, Michiko; Kato, Fuminori; Hisatsune, Junzo; Tsuruda, Keiko; Koizumi, Koichi; Tatsukawa, Nobuyuki; Takeda, Kazuya; Sugai, Motoyuki

doi:10.1111/1348-0421.12359

Cited by 22 publications

(19 citation statements)

References 43 publications

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“…ABC-1 suppresses S . aureus protein A (SpA) expression and prevents the accumulation of polysaccharide intercellular adhesin (PIA) 19 . Therefore, it is possible that some of the hits identified from the C .…”

Section: Resultsmentioning

confidence: 99%

Suppression of Staphylococcus aureus biofilm formation and virulence by a benzimidazole derivative, UM-C162

Kong

Chee

Richter

et al. 2018

Sci Rep

110

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Staphylococcus aureus is a major cause of nosocomial infections and secretes a diverse spectrum of virulence determinants as well as forms biofilm. The emergence of antibiotic-resistant S. aureus highlights the need for alternative forms of therapeutics other than conventional antibiotics. One route to meet this need is screening small molecule derivatives for potential anti-infective activity. Using a previously optimized C. elegans – S. aureus small molecule screen, we identified a benzimidazole derivative, UM-C162, which rescued nematodes from a S. aureus infection. UM-C162 prevented the formation of biofilm in a dose-dependent manner without interfering with bacterial viability. To examine the effect of UM-C162 on the expression of S. aureus virulence genes, a genome-wide transcriptome analysis was performed on UM-C162-treated pathogen. Our data indicated that the genes associated with biofilm formation, particularly those involved in bacterial attachment, were suppressed in UM-C162-treated bacteria. Additionally, a set of genes encoding vital S. aureus virulence factors were also down-regulated in the presence of UM-C162. Further biochemical analysis validated that UM-C162-mediated disruption of S. aureus hemolysins, proteases and clumping factors production. Collectively, our findings propose that UM-C162 is a promising compound that can be further developed as an anti-virulence agent to control S. aureus infections.

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Section: Resultsmentioning

confidence: 99%

Suppression of Staphylococcus aureus biofilm formation and virulence by a benzimidazole derivative, UM-C162

Kong

Chee

Richter

et al. 2018

Sci Rep

110

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show abstract

“…We evaluated the biofilm-elaborating ability of clinical isolates in Japan and found that TF2758, which was isolated from an atheroma, is an extremely high biofilm producer ( 17 ). Whole-genome sequencing and a microarray analysis of TF2758 discovered a spontaneous mutation in a putative transcriptional regulator gene, within a 7-gene cluster, which was expressed at markedly higher levels than in a non-biofilm-elaborating control strain.…”

Section: Introductionmentioning

confidence: 99%

A Novel Repressor of the ica Locus Discovered in Clinically Isolated Super-Biofilm-Elaborating Staphylococcus aureus

Hisatsune

Hayashi

et al. 2017

mBio

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Staphylococcus aureus TF2758 is a clinical isolate from an atheroma and a super-biofilm-elaborating/polysaccharide intercellular adhesin (PIA)/poly-N-acetylglucosamine (PNAG)-overproducing strain (L. Shrestha et al., Microbiol Immunol 60:148–159, 2016, https://doi.org/10.1111/1348-0421.12359). A microarray analysis and DNA genome sequencing were performed to identify the mechanism underlying biofilm overproduction by TF2758. We found high transcriptional expression levels of a 7-gene cluster (satf2580 to satf2586) and the ica operon in TF2758. Within the 7-gene cluster, a putative transcriptional regulator gene designated rob had a nonsense mutation that caused the truncation of the protein. The complementation of TF2758 with rob from FK300, an rsbU-repaired derivative of S. aureus strain NCTC8325-4, significantly decreased biofilm elaboration, suggesting a role for rob in this process. The deletion of rob in non-biofilm-producing FK300 significantly increased biofilm elaboration and PIA/PNAG production. In the search for a gene(s) in the 7-gene cluster for biofilm elaboration controlled by rob, we identified open reading frame (ORF) SAOUHSC_2898 (satf2584). Our results suggest that ORF SAOUHSC_2898 (satf2584) and icaADBC are required for enhanced biofilm elaboration and PIA/PNAG production in the rob deletion mutant. Rob bound to a palindromic sequence within its own promoter region. Furthermore, Rob recognized the TATTT motif within the icaR-icaA intergenic region and bound to a 25-bp DNA stretch containing this motif, which is a critically important short sequence regulating biofilm elaboration in S. aureus. Our results strongly suggest that Rob is a long-sought repressor that recognizes and binds to the TATTT motif and is an important regulator of biofilm elaboration through its control of SAOUHSC_2898 (SATF2584) and Ica protein expression in S. aureus.

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“…In line with our results, Sambanthamoorthy et al () reported the anti‐biofilm activity of benzimidazole molecules, without having the bactericidal activity except for Helicobacter pylori , against Gram‐negative and Gram‐positive bacteria pathogens (Sambanthamoorthy et al, ). Recently, at 156 μM, benzimidazole was shown to inhibit S. aureus biofilm formation without bactericidal activity by binding to the biofilm proteins (Shrestha et al, ). Another chemical molecule, 4‐(benzylamino) cyclohexyl 2‐hydroxycinnamate has shown anti‐biofilm activity (MBIC 65 μg/mL) against UTI associated staphylococcal infection (Balamurugan et al, ).…”

Section: Resultsmentioning

confidence: 99%

In‐house chemical library repurposing: A case example for Pseudomonas aeruginosa antibiofilm activity and quorum sensing inhibition

Singh

Tripathi

Raj

et al. 2018

Drug Development Research

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Hit, Lead & Candidate Discovery Drug repurposing has become a recent trend in drug development programs, where previously developed drugs are explored for hit and redeveloped into potential therapeutic agents for new diseases. Globally, in any drug development program, a series of molecules are synthesized and evaluated for the hypothesized activity. Hits are developed into lead molecules or drugs, whereas the negative ones are shelved in the lab with no immediate use. We in this project took the previously sidelined small chemical molecules to the next level of utility, where previously developed in‐house small molecules library are tested for the unexplored biological relevant activity. As biofilm formation and quorum sensing play a vital role in bacterial pathogenesis, we believe that they could be one of the most effective targets for antimicrobial agents. In this study, we report the evaluation of 50 different compounds for anti‐biofilm and anti‐quorum sensing activity against Pseudomonas aeruginosa. Out of the screened compounds, three hydrazine‐carboxamide hybrid derivatives showed promising anti‐biofilm property and inhibition of pyocyanin production without any direct antimicrobial activity and cytotoxicity issues. Hydrazine‐carboxamide hybrids can be a new class and promising leads for further anti‐biofilm and anti‐virulence development against microbial infections.

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Inhibitory effects of antibiofilm compound 1 against Staphylococcus aureus biofilms

Cited by 22 publications

References 43 publications

Suppression of Staphylococcus aureus biofilm formation and virulence by a benzimidazole derivative, UM-C162

Suppression of Staphylococcus aureus biofilm formation and virulence by a benzimidazole derivative, UM-C162

A Novel Repressor of the ica Locus Discovered in Clinically Isolated Super-Biofilm-Elaborating Staphylococcus aureus

In‐house chemical library repurposing: A case example for Pseudomonas aeruginosa antibiofilm activity and quorum sensing inhibition

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