Neuroprotective effects on microglia and insights into the structure-activity relationship of an antioxidant peptide isolated from Pelophylax perezi.

Tryptophyllins constitute a heterogeneous group of peptides that are one of the first classes of peptides identified from amphibian's skin secretions. Here, we report the structural characterization and antioxidant properties of a novel tryptophyllin-like peptide, named PpT-2, isolated from the Iberian green frog Pelophylax perezi. The skin secretion of P. perezi was obtained by electrical stimulation and fractionated using RP-HPLC. De novo peptide sequencing was conducted using MALDI MS/MS. The primary structure of PpT-2 (FPWLLS-NH2 ) was confirmed by Edman degradation and subsequently investigated using in silico tools. PpT-2 shared physicochemical properties with other well-known antioxidants. To test PpT-2 for antioxidant activity in vitro, the peptide was synthesized by solid phase and assessed in the chemical-based ABTS and DPPH scavenging assays. Then, a flow cytometry experiment was conducted to assess PpT-2 antioxidant activity in oxidatively challenged murine microglial cells. As predicted by the in silico analyses, PpT-2 scavenged free radicals in vitro and suppressed the generation of reactive species in PMA-stimulated BV-2 microglia cells. We further explored possible bioactivities of PpT-2 against prostate cancer cells and bacteria, against which the peptide exerted a moderate antiproliferative effect and negligible antimicrobial activity. The biocompatibility of PpT-2 was evaluated in cytotoxicity assays and in vivo toxicity with Galleria mellonella. No toxicity was detected in cells treated with up to 512 µg/ml and in G. mellonella treated with up to 40 mg/kg PpT-2. This novel peptide, PpT-2, stands as a promising peptide with potential therapeutic and biotechnological applications, mainly for the treatment/prevention of neurodegenerative disorders.

Mechanistic Insights into the Leishmanicidal and Bactericidal Activities of Batroxicidin, a Cathelicidin-Related Peptide from a South American Viper (Bothrops atrox).

Snake venoms are important sources of bioactive molecules, including those with antiparasitic activity. Cathelicidins form a class of such molecules, which are produced by a variety of organisms. Batroxicidin (BatxC) is a cathelicidin found in the venom of the common lancehead (Bothrops atrox). In the present work, BatxC and two synthetic analogues, BatxC(C-2.15Phe) and BatxC(C-2.14Phe)des-Phe1, were assessed for their microbicidal activity. All three peptides showed a broad-spectrum activity on Gram-positive and -negative bacteria, as well as promastigote and amastigote forms of Leishmania (Leishmania) amazonensis. Circular dichroism (CD) and nuclear magnetic resonance (NMR) data indicated that the three peptides changed their structure upon interaction with membranes. Biomimetic membrane model studies demonstrated that the peptides exert a permeabilization effect in prokaryotic membranes, leading to cell morphology distortion, which was confirmed by atomic force microscopy (AFM). The molecules considered in this work exhibited bactericidal and leishmanicidal activity at low concentrations, with the AFM data suggesting membrane pore formation as their mechanism of action. These peptides stand as valuable prototype drugs to be further investigated and eventually used to treat bacterial and protozoal infections.

Pyranoanthocyanins Interfering with the Quorum Sensing of Pseudomonas aeruginosa and Staphylococcus aureus.

Bacterial quorum sensing (QS) is a cell-cell communication system that regulates several bacterial mechanisms, including the production of virulence factors and biofilm formation. Thus, targeting microbial QS is seen as a plausible alternative strategy to antibiotics, with potentiality to combat multidrug-resistant pathogens. Many phytochemicals with QS interference activity are currently being explored. Herein, an extract and a compound of bioinspired origin were tested for their ability to inhibit biofilm formation and interfere with the expression of QS-related genes in Pseudomonas aeruginosa and Staphylococcus aureus. The extract, a carboxypyranoanthocyanins red wine extract (carboxypyrano-ant extract), and the pure compound, carboxypyranocyanidin-3-O-glucoside (carboxypyCy-3-glc), did not cause a visible effect on the biofilm formation of the P. aeruginosa biofilms; however, both significantly affected the formation of biofilms by the S. aureus strains, as attested by the crystal violet assay and fluorescence microscopy. Both the extract and the pure compound significantly interfered with the expression of several QS-related genes in the P. aeruginosa and S. aureus biofilms, as per reverse transcription-quantitative polymerase chain reaction (RT-qPCR) results. Indeed, it was possible to conclude that these molecules interfere with QS at distinct stages and in a strain-specific manner. An extract with anti-QS properties could be advantageous because it is easily obtained and could have broad, antimicrobial therapeutic applications if included in topical formulations.

"Clicking" an Ionic Liquid to a Potent Antimicrobial Peptide: On the Route towards Improved Stability.

A covalent conjugate between an antibacterial ionic liquid and an antimicrobial peptide was produced via "click" chemistry, and found to retain the parent peptide's activity against multidrug-resistant clinical isolates of Gram-negative bacteria, and antibiofilm action on a resistant clinical isolate of Klebsiella pneumoniae, while exhibiting much improved stability towards tyrosinase-mediated modifications. This unprecedented communication is a prelude for the promise held by ionic liquids -based approaches as tools to improve the action of bioactive peptides.

Intragenic Antimicrobial Peptide Hs02 Hampers the Proliferation of Single- and Dual-Species Biofilms of P. aeruginosa and S. aureus: A Promising Agent for Mitigation of Biofilm-Associated Infections.

Pseudomonas aeruginosa and Staphylococcus aureus are two major pathogens involved in a large variety of infections. Their co-occurrence in the same site of infection has been frequently reported and is linked to enhanced virulence and difficulty of treatment. Herein, the antimicrobial and antibiofilm activities of an intragenic antimicrobial peptide (IAP), named Hs02, which was uncovered from the human unconventional myosin 1H protein, were investigated against several P. aeruginosa and S. aureus strains, including multidrug-resistant (MDR) isolates. The antibiofilm activity was evaluated on single- and dual-species biofilms of P. aeruginosa and S. aureus. Moreover, the effect of peptide Hs02 on the membrane fluidity of the strains was assessed through Laurdan generalized polarization (GP). Minimum inhibitory concentration (MIC) values of peptide Hs02 ranged from 2 to 16 µg/mL against all strains and MDR isolates. Though Hs02 was not able to hamper biofilm formation by some strains at sub-MIC values, it clearly affected 24 h preformed biofilms, especially by reducing the viability of the bacterial cells within the single- and dual-species biofilms, as shown by confocal laser scanning microscopy (CLSM) and atomic force microscopy (AFM) images. Laurdan GP values showed that Hs02 induces membrane rigidification in both P. aeruginosa and S. aureus. Peptide Hs02 can potentially be a lead for further improvement as an antibiofilm agent.

Synthesis of novel sulfide-based cyclic peptidomimetic analogues to solonamides.

Eight new sulfide-based cyclic peptidomimetic analogues of solonamides A and B have been synthesized via solid-phase peptide synthesis and SN2' reaction on a Morita-Baylis-Hillman (MBH) residue introduced at the N-terminal of a tetrapeptide. This last step takes advantage of the electrophilic feature of the MBH residue and represents a new cyclization strategy occurring. The analogues were prepared in moderate overall yields and did not show toxic effects on Staphylococcus aureus growth and were not toxic to human fibroblasts. Two of them inhibited the hemolytic activity of S. aureus, suggesting an interfering action in the bacterial quorum sensing similar to the one already reported for solonamides.

River water analysis using a multiparametric approach: Portuguese river as a case study.

The Ave River in northern Portugal has a history of riverbanks and water quality degradation. The river water quality was assessed by physicochemical, biological (macroinvertebrates) and microbiological (Enterococcus spp. and Escherichia coli) parameters in six locations (A-F, point A being the nearest to the source) throughout its course during a year. Epilithic biofilms were studied through polymerase chain reaction denaturing gradient gel electrophoresis (PCR-DGGE). Antimicrobial susceptibility testing helped with selecting isolates (n = 149 E. coli and n = 86 enterococci) for further genetic characterization. Pursuant to physicochemical and macroinvertebrates-based parameters, the river water was of reasonable quality according to European legislation (Directive 2000/60/EC). However, the microbiological analysis showed increased fecal contamination downstream from point C. At point D, four carbapenem-resistant E. coli isolates were recovered. Paradoxically, point D was classified as a point of 'Good Water Quality' according to macroinvertebrates results. Point F presented the highest contamination level and incidence of multidrug-resistant (MDR) isolates in the water column (13 MDR enterococci out of 39 and 33 MDR E. coli out of 97). Epilithic biofilms showed higher diversity in pristine points (A and B). Thus, biological and microbiological parameters used to assess the water quality led to divergent results; an outcome that reinforces the need for a holistic evaluation.

Chemical Composition, Antibacterial, Antibiofilm and Synergistic Properties of Essential Oils from Eucalyptus globulus Labill. and Seven Mediterranean Aromatic Plants.

Essential oils (EOs) from Eucalyptus globulus Labill. ssp. globulus and from Mediterranean autochthonous aromatic plants - Thymus mastichina L., Mentha pulegium L., Rosmarinus officinalis L., Calamintha nepeta (L.) Savi ssp. nepeta, Cistus ladanifer L., Foeniculum vulgare L., Dittrichia viscosa (L.) Greuter ssp. viscosa - were extracted by hydrodistillation and characterized by GC-FID and NMR spectroscopy. EOs were evaluated for antimicrobial properties against several bacterial strains, using diverse methods, namely, the agar disc-diffusion method, the microdilution method, the crystal violet assay and the Live/Dead staining for assessment of biofilm formation. Potential synergy was assessed by a checkerboard method. EOs of R. officinalis and C. ladanifer showed a predominance in monoterpene hydrocarbons (> 60%); EOs of C. nepeta, M. pulegium, T. mastichina, E. globulus and F. vulgare were rich in oxygenated monoterpenes (62 - 96%) whereas EO of D. viscosa was mainly composed of oxygenated sesquiterpenes (54%). All EOs showed antimicrobial activity; M. pulegium and E. globulus generally had the strongest antimicrobial activity. EO of C. nepeta was the most promising in hampering the biofilm formation. The combinations D. viscosa/C. nepeta and E. globulus/T. mastichina were synergistic against Staphylococcus aureus. These results support the notion that EOs from the aromatic plants herein reported should be further explored as potential pharmaceuticals and/or food preservatives.

Bacterial isolates from infected wounds and their antibiotic susceptibility pattern: some remarks about wound infection.

Wound infection plays an important role in the development of chronicity, delaying wound healing. This study aimed to identify the bacterial pathogens present in infected wounds and characterise their resistance profile to the most common antibiotics used in therapy. Three hundred and twelve wound swab samples were collected from 213 patients and analysed for the identification of microorganisms and for the determination of their antibiotic susceptibility. Patients with diverse type of wounds were included in this retrospective study, carried out from March to September 2012. A total of 28 species were isolated from 217 infected wounds. The most common bacterial species detected was Staphylococcus aureus (37%), followed by Pseudomonas aeruginosa (17%), Proteus mirabilis (10%), Escherichia coli (6%) and Corynebacterium spp. (5%). Polymicrobial infection was found in 59 (27·1%) of the samples and was mainly constituted with two species. The most common association was S. aureus/P. aeruginosa. All Gram-positives were susceptible to vancomycin and linezolid. Gram-negatives showed quite high resistance to the majority of antibiotics, being amikacin the most active against these bacteria. This study is mostly oriented to health care practitioners who deal with wound management, making them aware about the importance of wound infection and helping them to choose the adequate treatment options to control microbial infection in wounds.

High prevalence of multidrug-resistant Escherichia coli and Enterococcus spp. in river water, upstream and downstream of a wastewater treatment plant.

In this study, microbial quality and antimicrobial resistance of faecal bacteria from a Portuguese river were assessed. River water samples collected upstream and downstream of a wastewater treatment plant, throughout a 3-month period, were used for the enumeration of Escherichia coli and Enterococcus spp. The highest numbers found for E. coli and enterococci were 1.1 × 104 and 1.2 × 104 colony forming units (CFU)/100 ml, respectively. In total, 144 isolates of E. coli and 144 of enterococci were recovered and tested for antimicrobial susceptibility; 104 E. coli and 78 Enterococcus spp. showed resistance to one or more antimicrobial drugs. Overall, 70 and 32 different resistance patterns were found for E. coli and enterococci, respectively. One E. coli showed resistance to imipenem and 29 isolates were extended spectrum ß-lactamase-producers. Multidrug-resistant E. coli belonged mostly to groups A, B1 and group D. Enterococcus spp. were mostly resistant to rifampicin, tetracycline, azithromycin and erythromycin; six isolates showed resistance to vancomycin, presenting the VanA phenotype. The high levels of E. coli and enterococci and the remarkable variety of antimicrobial resistance profiles, reinforces the theory that these river waters can be a pool of antimicrobial resistance determinants, which can be easily spread among different bacteria and reach other environments and hosts.

New isocoumarin derivatives and meroterpenoids from the marine sponge-associated fungus Aspergillus similanensis sp. nov. KUFA 0013.

Two new isocoumarin derivatives, including a new 5-hydroxy-8-methyl-2H, 6H-pyrano[3,4-g]chromen-2,6-dione (1) and 6,8-dihydroxy-3,7-dimethylisocoumarin (2b), a new chevalone derivative, named chevalone E (3), and a new natural product pyripyropene S (6) were isolated together with 6, 8-dihydroxy-3-methylisocoumarin (2a), reticulol (2c), p-hydroxybenzaldehyde, chevalone B, chevalone C, S14-95 (4), and pyripyropene E (5) from the ethyl acetate extract of the undescribed marine sponge-associated fungus Aspergillus similanensis KUFA 0013. The structures of the new compounds were established based on 1D and 2D NMR spectral analysis, and in the case of compound 3, X-ray analysis was used to confirm its structure and the absolute configuration of its stereogenic carbons. Compounds 1, 2a-c and 3-6 were evaluated for their antimicrobial activity against Gram-positive and Gram-negative bacteria, Candida albicans ATCC 10231, and multidrug-resistant isolates from the environment. Chevalone E (3) was found to show synergism with the antibiotic oxacillin against methicillin-resistant Staphylococcus aureus (MRSA).

Antibacterial and antibiofilm activities of tryptoquivalines and meroditerpenes isolated from the marine-derived fungi Neosartorya paulistensis, N. laciniosa, N. tsunodae, and the soil fungi N. fischeri and N. siamensis.

A new meroditerpene, sartorypyrone C (5), was isolated, together with the known tryptoquivalines L (1a), H (1b), F (1c), 3'-(4-oxoquinazolin-3-yl) spiro [1H-indole-3,5']-2,2'-dione (2) and 4(3H)-quinazolinone (3), from the culture of the marine sponge-associated fungus Neosartorya paulistensis (KUFC 7897), while reexamination of the fractions remaining from a previous study of the culture of the diseased coral-derived fungus N. laciniosa (KUFC 7896) led to isolation of a new tryptoquivaline derivative tryptoquivaline T (1d). Compounds 1a-d, 2, 3, and 5, together with aszonapyrones A (4a) and B (4b), chevalones B (6) and C (7a), sartorypyrones B (7b) and A (8), were tested for their antibacterial activity against four reference strains (Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa), as well as the environmental multidrug-resistant isolates. Only aszonapyrone A (4a) and sartorypyrone A (8) exhibited significant antibacterial activity as well as synergism with antibiotics against the Gram-positive multidrug-resistant strains. Antibiofilm assays of aszonapyrone A (4a) and sartorypyrone A (8) showed that practically no biofilm was formed in the presence of their 2× MIC and MIC. However, the presence of a sub-inhibitory concentration of ½ MIC of 4a and 8 was found to increase the biofilm production in both reference strain and the multidrug-resistant isolates of S. aureus.

Antibacterial and EGFR-tyrosine kinase inhibitory activities of polyhydroxylated xanthones from Garcinia succifolia.

Chemical investigation of the methanol extract of the wood of Garcinia succifolia Kurz (Clusiaceae) led to the isolation of 1,5-dihydroxyxanthone (1), 1,7-dihydroxyxanthone (2), 1,3,7-trihydroxyxanthone (3), 1,5,6-trihydroxyxanthone (4), 1,6,7-trihydroxyxanthone (5), and 1,3,6,7-tetrahydroxyxanthone (6). All of the isolated xanthones were evaluated for their antibacterial activity against bacterial reference strains, two Gram-positive (Staphylococcus aureus ATTC 25923, Bacillus subtillis ATCC 6633) and two Gram-negative (Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853), and environmental drug-resistant isolates (S. aureus B1, Enteroccoccus faecalis W1, and E. coli G1), as well as for their epidermal growth factor receptor (EGFR) of tyrosine kinase inhibitory activity. Only 1,5,6-trihydroxy-(4), 1,6,7-trihydroxy-(5), and 1,3,6,7-tetrahydroxyxanthones (6) exhibited antibacterial activity against Gram-positive bacteria, however none was active against vancomycin-resistant E. faecalis. Additionally, 1,7-dihydroxyxanthone (2) showed synergism with oxacillin, but not with ampicillin. On the other hand, only 1,5-dihydroxyxanthone (1) and 1,7-dihydroxyxanthone (2) were found to exhibit the EGFR-tyrosine kinase inhibitory activity, with IC50 values of 90.34 and 223 nM, respectively.

Dental Implant Surface Decontamination and Surface Change of an Electrolytic Method versus Mechanical Approaches: A Pilot In Vitro Study.

Dental implants are the preferred fixed oral rehabilitation for replacing lost teeth. When peri-implant tissues become inflamed, the removal of plaque accumulating around the implant becomes imperative. Recently, several new strategies have been developed for this purpose, with electrolytic decontamination showing increased potential compared to traditional mechanical strategies. In this in vitro pilot study, we compare the efficacy of an electrolytic decontaminant (Galvosurge®) with an erythritol jet system (PerioFlow®) and two titanium brushes (R-Brush™ and i-Brush™) in removing Pseudomonas aeruginosa PAO1 biofilms from implants. Changes in the implant surface after each approach were also evaluated. Twenty titanium SLA implants were inoculated with P. aeruginosa and then randomly assigned to each treatment group. After treatment, decontamination efficacy was assessed by quantifying colony-forming units (log10 CFU/cm2) from each implant surface. Scanning electron microscopy was used to analyse changes in the implant surface. With the exception of R-Brush, all treatment strategies were similarly effective in removing P. aeruginosa from implants. Major surface changes were observed only in implants treated with titanium brushes. In conclusion, this pilot study suggests that electrolytic decontamination, erythritol-chlorhexidine particle jet system and i-Brush™ brushing have similar performance in removing P. aeruginosa biofilm from dental implants. Further studies are needed to evaluate the removal of more complex biofilms. Titanium brushes caused significant changes to the implant surface, the effects of which need to be evaluated.

Laser irradiation effect on Staphylococcus aureus and Pseudomonas aeruginosa biofilms isolated from venous leg ulcer.

Chronic wounds, including diabetic foot ulcers, pressure ulcers and venous leg ulcers, represent a significant cause of morbidity in developed countries, predominantly in older patients. The aetiology of these wounds is probably multifactorial, but the role of bacteria in their pathogenesis is still unclear. Moreover, the presence of bacterial biofilms has been considered an important factor responsible for wounds chronicity. We aimed to investigate the laser action as a possible biofilm eradicating strategy, in order to attempt an additional treatment to antibiotic therapy to improve wound healing. In this work, the effect of near-infrared (NIR) laser was evaluated on mono and polymicrobial biofilms produced by two pathogenic bacterial strains, Staphylococcus aureus PECHA10 and Pseudomonas aeruginosa PECHA9, both isolated from a chronic venous leg ulcer. Laser effect was assessed by biomass measurement, colony forming unit count and cell viability assay. It was shown that the laser treatment has not affected the biofilms biomass neither the cell viability, although a small disruptive action was observed in the structure of all biofilms tested. A reduction on cell growth was observed in S. aureus and in polymicrobial biofilms. This work represents an initial in vitro approach to study the influence of NIR laser treatment on bacterial biofilms in order to explain its potentially advantageous effects in the healing process of chronic infected wounds.

Managing Oral Health in the Context of Antimicrobial Resistance.

The oral microbiome plays a major role in shaping oral health/disease state; thus, a main challenge for dental practitioners is to preserve or restore a balanced oral microbiome. Nonetheless, when pathogenic microorganisms install in the oral cavity and are incorporated into the oral biofilm, oral infections, such as gingivitis, dental caries, periodontitis, and peri-implantitis, can arise. Several prophylactic and treatment approaches are available nowadays, but most of them have been antibiotic-based. Given the actual context of antimicrobial resistance (AMR), antibiotic stewardship in dentistry would be a beneficial approach to optimize and avoid inappropriate or even unnecessary antibiotic use, representing a step towards precision medicine. Furthermore, the development of new effective treatment options to replace the need for antibiotics is being pursued, including the application of photodynamic therapy and the use of probiotics. In this review, we highlight the advances undergoing towards a better understanding of the oral microbiome and oral resistome. We also provide an updated overview of how dentists are adapting to better manage the treatment of oral infections given the problem of AMR.

Boosting Cosmeceutical Peptides: Coupling Imidazolium-Based Ionic Liquids to Pentapeptide-4 Originates New Leads with Antimicrobial and Collagenesis-Inducing Activities.

Following our previous reports on dual-action antibacterial and collagenesis-inducing hybrid peptide constructs based on "pentapeptide-4" (PP4, with amino acid sequence KTTKS), whose N-palmitoyl derivative is the well-known cosmeceutical ingredient Matrixyl, herein we disclose novel ionic liquid/PP4 conjugates (IL-KTTKS). These conjugates present potent activity against either antibiotic-susceptible strains or multidrug resistant clinical isolates of both Gram-positive and Gram-negative bacterial species belonging to the so-called "ESKAPE" group of pathogens. Noteworthy, their antibacterial activity is preserved in simulated wound fluid, which anticipates an effective action in the setting of a real wound bed. Moreover, their collagenesis-inducing effects in vitro are comparable to or stronger than those of Matrixyl. Altogether, IL-KTTKS exert a triple antibacterial, antifungal, and collagenesis-inducing action in vitro. These findings provide solid grounds for us to advance IL-KTTKS conjugates as promising leads for future development of topical treatments for complicated skin and soft tissue infections (cSSTI). Further studies are envisaged to incorporate IL-conjugates into suitable nanoformulations, to reduce toxicity and/or improve resistance to proteolytic degradation. IMPORTANCE As life expectancy increases, diseases causing chronic wound infections become more prevalent. Diabetes, peripheral vascular diseases, and bedridden patients are often associated with non-healing wounds that become infected, resulting in high morbidity and mortality. This is exacerbated by the fact that microbes are becoming increasingly resistant to antibiotics, so efforts must converge toward finding efficient therapeutic alternatives. Recently, our team identified a new type of constructs that combine (i) peptides used in cosmetics to promote collagen formation with (ii) imidazolium-based ionic liquids, which have antimicrobial and skin penetration properties. These constructs have potent wide-spectrum antimicrobial action, including against multidrug-resistant Gram-positive and Gram-negative bacteria, and fungi. Moreover, they can boost collagen formation. Hence, this is an unprecedented class of lead molecules toward development of a new topical medicine for chronically infected wounds.

How Insertion of a Single Tryptophan in the N-Terminus of a Cecropin A-Melittin Hybrid Peptide Changes Its Antimicrobial and Biophysical Profile.

In the era of antibiotic resistance, there is an urgent need for efficient antibiotic therapies to fight bacterial infections. Cationic antimicrobial peptides (CAMP) are promising lead compounds given their membrane-targeted mechanism of action, and high affinity towards the anionic composition of bacterial membranes. We present a new CAMP, W-BP100, derived from the highly active BP100, holding an additional tryptophan at the N-terminus. W-BP100 showed a broader antibacterial activity, demonstrating a potent activity against Gram-positive strains. Revealing a high partition constant towards anionic over zwitterionic large unilamellar vesicles and inducing membrane saturation at a high peptide/lipid ratio, W-BP100 has a preferential location for hydrophobic environments. Contrary to BP100, almost no aggregation of anionic vesicles is observed around saturation conditions and at higher concentrations no aggregation is observed. With these results, it is possible to state that with the incorporation of a single tryptophan to the N-terminus, a highly active peptide was obtained due to the π-electron system of tryptophan, resulting in negatively charged clouds, that participate in cation-π interactions with lysine residues. Furthermore, we propose that W-BP100 action can be achieved by electrostatic interactions followed by peptide translocation.

Disclosure of a Promising Lead to Tackle Complicated Skin and Skin Structure Infections: Antimicrobial and Antibiofilm Actions of Peptide PP4-3.1.

Efficient antibiotics are being exhausted, which compromises the treatment of infections, including complicated skin and skin structure infections (cSSTI) often associated with multidrug resistant (MDR) bacteria, methicillin-resistant S. aureus (MRSA) being the most prevalent. Antimicrobial peptides (AMP) are being increasingly regarded as the new hope for the post-antibiotic era. Thus, future management of cSSTI may include use of peptides that, on the one hand, behave as AMP and, on the other, are able to promote fast and correct skin rebuilding. As such, we combined the well-known cosmeceutical pentapeptide-4 (PP4), devoid of antimicrobial action but possessing collagenesis-boosting properties, with the AMP 3.1, to afford the chimeric peptide PP4-3.1. We further produced its N-methyl imidazole derivative, MeIm-PP4-3.1. Both peptide-based constructs were evaluated in vitro against Gram-negative bacteria, Gram-positive bacteria, and Candida spp. fungi. Additionally, the antibiofilm activity, the toxicity to human keratinocytes, and the activity against S. aureus in simulated wound fluid (SWF) were assessed. The chimeric peptide PP4-3.1 stood out for its potent activity against Gram-positive and Gram-negative bacteria, including against MDR clinical isolates (0.8 ≤ MIC ≤ 5.7 µM), both in planktonic form and in biofilm matrix. The peptide was also active against three clinically relevant species of Candida fungi, with an overall performance superior to that of fluconazole. Altogether, data reveal that PP4-3.1 is as a promising lead for the future development of new topical treatments for severe skin infections.