Lipoteichoic Acid Biosynthesis Inhibitors as Potent Inhibitors of S. aureus and E. faecalis Growth and Biofilm Formation

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecalis (VRE) have been deemed as serious threats by the CDC. Many chronic MRSA and VRE infections are due to biofilm formation. Biofilm are considered to be between 10–10,000 times more resistant to antibiotics, and therefore new chemical entities that inhibit and/or eradicate biofilm formation are needed. Teichoic acids, such as lipoteichoic acids (LTAs) and wall teichoic acids (WTAs), play pivotal roles in Gram-positive bacteria’s ability to grow, replicate, and form biofilms, making the inhibition of these teichoic acids a promising approach to fight infections by biofilm forming bacteria. Here, we describe the potent biofilm inhibition activity against MRSA and VRE biofilms by two LTA biosynthesis inhibitors HSGN-94 and HSGN-189 with MBICs as low as 0.0625 µg/mL against MRSA biofilms and 0.5 µg/mL against VRE biofilms. Additionally, both HSGN-94 and HSGN-189 were shown to potently synergize with the WTA inhibitor Tunicamycin in inhibiting MRSA and VRE biofilm formation.

Bisdemethoxycurcumin Reduces Methicillin-Resistant Staphylococcus aureus Expression of Virulence-Related Exoproteins and Inhibits the Biofilm Formation

“…This biofilm is Toxins 2021, 13, 804 2 of 10 recalcitrant in efforts to be eradicated by anti-bacterial agents, further limiting the efficacy of currently available antibiotics [10]. Biofilm formation is regulated by the quorumsensing (QS) system [11], and the hld gene is regarded as the most effective molecule in the Staphylococcal QS system [12]. The biofilm formation increases MRSA resistance to antibiotics by 10-10,000 times and is also the cause of many chronic MRSA infections [13].…”

Peptaibol-Containing Extracts of Trichoderma atroviride and the Fight against Resistant Microorganisms and Cancer Cells

“…We also observed that the percentage of growth in the presence of LTA and peptaibol-containing extract was higher than that of the control. LTA is a key element of the biofilm of S. aureus [ 34 ]. To protect from peptaibols, S. aureus may form a biofilm, also using available LTA.…”

Bacterial Biofilms and Their Implications in Pathogenesis and Food Safety

“…Tunicamycin treatment also reduced S. aureus adhesion to epithelial cells and reduced NF-κB activation and inflammatory response, suggesting that LTA is an important virulence factor promoting biofilm formation and pathogenesis in this bacterium [ 77 ]. More recently, inhibition of LTA by two synthetic inhibitors, HSGN-94 and HSGN-189, showed significant suppression of biofilm formation and synergistic biofilm inhibition when combined with tunicamycin [ 111 ].…”