Novel Arginine End-Tagging Antimicrobial Peptides to Combat Multidrug-Resistant Bacteria

Abstract

The emergence of multidrug-resistant microorganisms has been termed one of the most common global health threats, emphasizing the discovery of new antibacterial agents. To address this issue, we engineered peptides harboring “RWWWR” as a central motif plus arginine (R) end-tagging and then tested them in vitro and in vivo. Our results demonstrate that Pep 6, one of the engineered peptides, shows great potential in combating Escherichia coli bacteremia and the Staphylococcus aureus skin burn infection model, which induces a 62–90% reduction in bacterial burden. Remarkably, after long serial passages of S. aureus and E. coli for 30 days, Pep 6 is still highly efficient in killing pathogens, compared with 64- and 128-fold increase in minimal inhibitory concentrations (MICs) for vancomycin and polymyxin B, respectively. We also found that Pep 6 exhibited robust biofilm-inhibiting activity and eliminated 61.33% of the mature methicillin-resistant Staphylococcus aureus (MRSA) biofilm with concentration in the MIC level. These results suggest that the RWWWR motif and binding of arginine end-tagging could be harnessed as a new agent for combating multidrug-resistant bacteria.

Membrane-Active Nonivamide Derivatives as Effective Broad-Spectrum Antimicrobials: Rational Design, Synthesis, and Biological Evaluation

“…Several cationic groups have been widely used to endow the cationic characteristics of antibacterial agents, such as amine groups, guanidine group, and arginine that provides cation for natural AMPs. − To study the effect of different cationic substituents on the antibacterial activity of nonivamide derivatives, the raw material nonivamide with a length of four-carbon spacer was coupled with primary amine, guanidine, H-arginine (Arg)-OMe, H-Arg-Arg-Arg-OMe, tertiary amine (diethylamine-coupled), secondary amine (ethylamine-coupled), and tertiary amine ( N 1 -(3-(dimethylamino)­propyl)- N 3 , N 3 -dimethylpropane-1,3-diamine-coupled) to yield compounds 11 , 19 , 27 , 28 , 29 , 30 , and 31 , respectively. As shown in Table , among these compounds, the guanidine-coupled 19 displayed the best antibacterial activity against Gram-positive bacteria (MICs = 6.25–12.5 μg/mL), while the alkylamine-coupled compounds 11 and 29 – 31 showed the worst antibacterial activity (MICs >50 μg/mL).…”

“…13 C NMR (100 MHz, CD 3 OD) δ 176. 12, 169.73, 150.95, 149.16, 133.12, 121.20, 114.71, 113.06, 70.35, 56.49, 43.83, 42.46, 37.12, 32.97, 30.68, 30.66, 30.65, 30.63, 30.49, 30.42, 30.37, 30.34, 30.32, 30.27, 30.25, 29.90 (25). To a solution of nonivamide (200 mg, 0.68 mmol) in DMF (10 mL), ethyl bromoacetate (226.2 μL, 2.05 mmol), K 2 CO 3 (235.5 mg, 1.70 mmol), and KI (282.9 mg, 1.70 mmol) were added.…”

“…J = 6.8 Hz, 3H).13 C NMR (100 MHz, CD 3 OD) δ 176 25,. 173.23, 171.57, 151.21, 147.87, 135.58, 121.07, 117.26, 112.96, 101.34, 70.62, 56.49, 52.99, 52.74, 43.72, 41.75, 37.10, 32.97, 30.41, 30.32, 30.30, 29.87, 27.09, 26.11, 23.70, 14.43.…”

Anaerobic fermentation featuring wheat bran and rice bran realizes the clean transformation of Chinese cabbage waste into livestock feed

“…Furthermore, a high incidence of aerobic bacteria raises nutrient loss and leads to aerobic spoilage. Bacteria that are biofilm-formed can induce various infections and cause risks to animal health (Shang et al, 2021). Therefore, the mixed ratios in W3 and R2 were recommended for constructing a system to recycle Chinese cabbage waste from a microbiological safety viewpoint.…”

Antimicrobial Peptide-Loaded Gelatinase-Responsive Photothermal Nanogel for the Treatment of Staphylococcus aureus-Infected Wounds

“…Inspired by nature, antimicrobial peptides (AMPs) and related mimics have been widely studied because of their unique antibacterial mechanisms. In addition to directly acting on the cell membrane for physical damage, AMPs can also indirectly perform antibacterial-related immune regulation, and multiple mechanisms make them exhibit efficient antibacterial activity. , Different from the interaction between traditional antibiotics and bacteria-specific receptors, AMPs attack the relatively conserved structure of bacterial evolution through different mechanisms and pathways, thus greatly inhibiting the tendency of further mutation in multidrug-resistant (MDR) bacteria. − However, the remarkable antibacterial activity of a single AMP is mostly aimed at planktonic bacteria, and the biofilm formed by the aggregation of multiple bacteria can prevent the infiltration of AMPs, thereby reducing the effective bactericidal concentration . Therefore, in the face of severe infection, people tend to use multimechanism synergistic treatment methods, in which physical heat-based photothermal therapy (PTT) has attracted much attention in the antibacterial field because of its advantages such as low toxicity, minimally invasive, and high space–time resolution. − …”