Multidrug resistant infections are plaguing the healthcare sector over the past few decades with limited treatment options. To overcome this problem, the authors synthesize a series of novel guanidinium‐functionalized polypeptides. Specifically, poly(l‐lysine) (PLL) with different lengths is first synthesized by ring‐opening polymerization of Nε‐benzyloxycarbonyl‐l‐lysine‐N‐carboxyanhydride (Lys(Z)‐NCA) followed by functionalization with a guanidinium‐functional group to obtain guanidinium‐functionalized PLL (PLL‐Gua). To study the effect of hydrophobicity on antimicrobial activity, relatively more hydrophobic leucine‐NCA monomer or hydrophobic vitamin E moiety is introduced to PLL‐Gua. These polypeptides are characterized for antimicrobial activity against a panel of microbes including multidrug‐resistant bacteria, and hemolytic activity. Among all the polypeptides, PLL22‐Gua is most effective against bacteria and yeast. Particularly, excellent bactericidal activity is observed against Staphylococcus aureus and MRSA. PLL22‐Gua kills bacteria mainly by membrane translocation. In addition, PLL22‐Gua kills MRSA with low resistance frequency (<3.3 × 10−8). In an MRSA‐caused wound infection mouse model, two‐day treatment (twice daily) with 10, 20, or 40 mg per kg of PLL22‐Gua shows up to 99.5% bacterial removal. Moreover, no acute dermal toxicity is observed even at a dose of 200 mg per kg. These promising results show the excellent potential of PLL22‐Gua as an antimicrobial agent against multidrug‐resistant infection in vivo.

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Rapidly resolving microstructure and function from thick biological samples is a critical requirement from basic research to clinical diagnosis. The need for physical sectioning leads to limitations in the speed, cost, or ease of sample preparation and imaging. We introduce a fluorescence microscope with deep ultraviolet illumination via omnidirectional fibre optics, based on the concept of microscopy with ultraviolet surface excitation (MUSE). We further exploited precise control of directional illumination to produce 3D reconstructions of surface microtopography from 2D images. Our technology is applicable to diverse sample types, ranging from single cells and 3D cultures to large tissue samples while utilising conventional, widely available objective lenses in a compact and portable implementation. We demonstrated the use of our microscope with important fluorescent assays through quantitative viability studies in single cells to whole organs, organ-level studies comparable to standard H&E histology, and multiplexed immunohistochemistry staining. We also explored the potential for microtopography to provide additional insight into vascular and tissue texture and heterogeneity studies. This technology fills long-standing technological gaps in both the laboratory and clinic for a general-purpose microscope that is simple, portable, and cheap that can provide near real-time biological insights.