Search Results (139)

This study evaluated the antimicrobial efficacy of cefiderocol and various forms of silver (ionic and nanoparticulate) as potential components of wound-dressing reagents against both reference and multidrug-resistant (MDR) Gram-negative bacteria. The anticipated synergistic effect between cefiderocol and nanosilver was not consistently observed; in fact, for reference strains, the combination was less effective than cefiderocol alone. However, in MDR and cefiderocol-resistant A. baumannii strains, combining both agents enhanced antibacterial efficacy. Notably, the effectiveness of silver did not increase with concentration, and low or medium nanosilver concentrations were often more effective. Mechanistically, high concentrations of silver may antagonize cefiderocol’s action by inhibiting bacterial surface proteins involved in siderophore-mediated uptake. Generalized linear modeling confirmed that the strain type, silver form, concentration, and their interactions significantly influenced inhibition zones. These findings highlight the importance of agent selection, concentration, and formulation in designing effective antimicrobial wound dressings. They also suggest that further research is needed to optimize such combination therapies for clinical use. Full article

The war between humans and bacteria started centuries ago. With the advent of antibiotics, there was a temporary ceasefire in this war, but the scenario soon started becoming worse with the emergence of drug-resistant strains within years of the deployment of antibiotics in the market. With the surge in the misuse of antibiotics, there was a drastic increase in the number of multidrug-resistant (MDR) and extensively drug-resistant bacterial strains, even to antibiotics like Methicillin and vancomycin, aggravating the healthcare scenario. The threat of MDR ESKAPE pathogens is particularly high in nosocomial infections, where biofilms formed by bacteria create a protective barrier that makes them highly resistant to antibiotics, complicating the treatment efforts. Scientists are looking at natural and sustainable solutions, as several studies have projected deaths contributed by drug-resistant bacteria to go beyond 50 million by 2050. Many plant-derived metabolites have shown excellent antibacterial and antibiofilm properties that can be tapped for combating superbugs. The present review explores the current status of various studies on antibacterial plant metabolites like alkaloids and flavonoids and their mechanisms in disrupting biofilms and killing bacteria by way of inhibiting key survival strategies of bacteria like motility, quorum-sensing, reactive oxygen species production, and adhesion. These mechanisms were found to be varied in Gram-positive, Gram-negative, and acid-fast bacteria like Mycobacterium tuberculosis, which will be discussed in detail. The successful tapping of the benefits of such plant-derived chemicals in combination with evolving techniques of nanotechnology and targeted drug delivery can go a long way in achieving the goal of One Health, which advocates the unity of multiple practices for the optimal health of people, animals, and the environment. Full article

The growing prevalence of bacterial infections and the alarming rise of antimicrobial resistance (AMR) have driven the need for innovative antimicrobial coatings for medical implants and biomaterials. However, implant surface properties, such as roughness, chemistry, and reactivity, critically influence biological interactions and must be engineered to ensure biocompatibility, corrosion resistance, and sustained antibacterial activity. This review evaluates three principal categories of antimicrobial agents utilized in surface functionalization: metal/metaloxide nanoparticles, antibiotics, and phytochemical compounds. Metal/metaloxide-based coatings, especially those incorporating silver (Ag), zinc oxide (ZnO), and copper oxide (CuO), offer broad-spectrum antimicrobial efficacy through mechanisms such as reactive oxygen species (ROS) generation and bacterial membrane disruption, with a reduced risk of resistance development. Antibiotic-based coatings enable localized drug delivery but often face limitations related to burst release, cytotoxicity, and diminishing effectiveness against multidrug-resistant (MDR) strains. In contrast, phytochemical-derived coatings—using bioactive plant compounds such as curcumin, eugenol, and quercetin—present a promising, biocompatible, and sustainable alternative. These agents not only exhibit antimicrobial properties but also provide anti-inflammatory, antioxidant, and osteogenic benefits, making them multifunctional tools for implant surface modification. The integration of these antimicrobial strategies aims to reduce bacterial adhesion, inhibit biofilm formation, and enhance tissue regeneration. By leveraging the synergistic effects of metal/metaloxide nanoparticles, antibiotics, and phytochemicals, next-generation implant coatings hold the potential to significantly improve infection control and clinical outcomes in implant-based therapies. Full article

In recent years, one of the most important issues in public health is the rapid growth of antibiotic resistance among pathogens. Multidrug-resistant (MDR) strains (mainly Enterobacteriaceae and non-fermenting bacilli) cause severe infections, against which commonly used pharmaceuticals are ineffective. Therefore, there is an urgent need for new treatment options and drugs with innovative mechanisms of action. Natural compounds, especially alkaloids, are showing promising potential in this area. This review focuses on the ability of the isoquinoline alkaloid berberine (BRB) to overcome various resistance mechanisms against conventional antimicrobial agents. BRB has demonstrated significant activity in inhibiting efflux pumps of the RND (Resistance-Nodulation-Cell Division) family, such as MexAB-OprM (P. aeruginosa) and AdeABC (A. baumannii). Moreover, BRB was able to decrease quorum sensing activity in both Gram-positive and Gram-negative pathogens, resulting in reduced biofilm formation and lower bacterial virulence. Additionally, BRB has been identified as a potential inhibitor of FtsZ, a key protein responsible for bacterial cell division. Particularly noteworthy, though requiring further investigation, are reports suggesting that BRB might inhibit β-lactamase enzymes, including NDM, AmpC, and ESβL types. The pleiotropic antibacterial actions of BRB, distinct from the mechanisms of traditional antibiotics, offer hope for breaking bacterial resistance. However, more extensive studies, especially in vivo, are necessary to fully evaluate the clinical potential of BRB and determine its practical applicability in combating antibiotic-resistant infections. Full article

One of the most urgent threats to public health worldwide is the ongoing rise of multidrug-resistant (MDR) bacterial strains. Among the most critical pathogens are MDR-Klebsiella pneumoniae strains. The lack of new antibiotics has led to an increased need for non-antibiotic antimicrobial therapies. Photodynamic therapy (PDT) has become increasingly significant in treating MDR bacteria. PDT uses photosensitizer compounds (PS) that generate reactive oxygen species (ROS) when activated by light. These ROS produce localized oxidative stress, damaging the bacterial envelope. A downside of PDT is the limited bioavailability of PSs in vivo, which can be enhanced by conjugating them with carriers like nanoparticles (NPs). Zinc nanoparticles possess antibacterial properties, decreasing the adherence and viability of microorganisms on surfaces. The additive or synergistic effect of the combined NP-PS could improve phototherapeutic action. Therefore, this study evaluated the effectiveness of the copper(I)-based PS CuC1 compound in combination with Zinc Oxide NP, ZnONP, to inhibit the growth of both MDR and sensitive K. pneumoniae strains. The reduction in bacterial viability after exposure to a PS/NP mixture activated by 61.2 J/cm² of blue light photodynamic treatment was assessed. The optimal PS/NP ratio was determined at 2 µg/mL of CuC1 combined with 64 µg/mL of ZnONP as the minimum effective concentration (MEC). The bacterial gene response aligned with a mechanism of photooxidative stress induced by the treatment, which damages the bacterial cell envelope. Additionally, we found that the PS/NP mixture is not harmful to mammalian cells, such as Hep-G2 and HEK-293. In conclusion, the CuC1/ZnONP combination could effectively aid in enhancing the antimicrobial treatment of infections caused by MDR bacteria. Full article

The use of antibiotics has greatly improved the treatment of bacterial infections; however, its abuse and misuse has led to a rapid rise in multidrug-resistant (MDR) bacteria. Therefore, the search for new antimicrobial strategies has become critical. Natural flavonoids, a class of widely existing phytochemicals, have gained significant research interest for their diverse biological activities and antibacterial effects on various drug-resistant bacteria. This review summarizes the latest research progress on flavonoids, with a particular focus on several flavonoids exhibiting certain antibacterial activity, and explores their antibacterial mechanisms, including disruption of cell membranes and cell walls, inhibition of proteins and nucleic acids, interference with signal transduction, suppression of efflux pump activity, and inhibition of biofilm formation and virulence factor production. Additionally, we have reviewed the synergistic combinations of flavonoids with antibiotics, such as the combination of quercetin with colistin or EGCG with tetracycline, which significantly enhance therapeutic efficacy. Full article

Background/Objectives: Pseudomonas aeruginosa (Psa) can circumvent antimicrobial chemotherapy, an ability enhanced by cigarette smoking (CS). This study probed potential benefits of combinations of anti-pseudomonal agents, and potential augmentation by a macrolide, in the absence or presence of cigarette smoke condensate (CSC). Methods: Two susceptible (WT: wild-type and DS: drug-sensitive) and one multidrug-resistant (MDR) strains of Psa were treated with amikacin, cefepime, and ciprofloxacin, individually and in combination, and with and without clarithromycin, followed by the measurement of planktonic growth and biofilm formation by spectrophotometry. Antibiotic interactions were determined using the fractional inhibitory concentration index (FICI) method. Effects on preformed biofilm density were measured following the addition of antibiotics: all procedures were performed in the absence and presence of CSC. Results: The minimal inhibitory concentrations (MICs) of the three agents ranged from 0.125 mg/L to 1 mg/L (WT and DS strains) and 16 mg/L to 64 mg/L (MDR strain), with all resistant to clarithromycin (125 mg/L). MIC values closely correlated with the antibiotic concentrations required to inhibit biofilm formation. FICI revealed synergism between most combinations, with augmentation by clarithromycin. Amikacin had the greatest effect on biofilm density, which was potentiated by combination with the other antibiotics, particularly clarithromycin. Exposure to CSC had variable, albeit modest, effects on bacterial growth and biofilm formation, but low concentrations increased biofilm mass and attenuated synergistic antimicrobial interactions and effects on biofilm density. Conclusions: Amikacin, cefepime, and ciprofloxacin, especially with clarithromycin, exhibit synergistic anti-pseudomonal activity and decrease preformed biofilm density. CSC attenuated these effects, illustrating the pro-infective potential of CS. Full article

Acinetobacter (A.) baumannii is a major nosocomial pathogen in human and veterinary medicine. The emergence of certain international clones (ICs), often with multidrug-resistant (MDR) phenotypes and biofilm formation (BF), facilitates its spread in clinical environments. The global rise in antimicrobial resistance demands alternative treatment strategies, such as antimicrobial peptides (AMPs). In this study, 45 human and companion animal MDR-A. baumannii isolates, belonging to the globally spread IC1, IC2 and IC7, were tested for antimicrobial resistance and biofilm-associated genes (BAGs) and their capacity for BF. Of these, 13 were used to test the inhibitory effect of AMPs on bacterial growth (BG) and BF through the application of a crystal violet assay. The two novel AMP variants Bac7(17) (target cell inactivation) and Pasmr5-17 (efflux pump inhibition) and the well-known AMP phenylalanine-arginine-β-naphthylamide (PAβN) were tested at concentrations of 1.95 to 1000 µg/mL. Based on whole-genome sequence data, identical patterns of BAGs were detected within the same IC. AMPs inhibited BG and BF in a dose-dependent manner. Bac7(17) and PAsmr5-17 were highly effective against BG, with growth inhibition (GI) of >99% (62.5 and 125 µg/mL, respectively). PAβN achieved only 95.7% GI at 1000 µg/mL. Similar results were obtained for BF. Differences between the ICs were found for both GI and BF when influenced by AMPs. PAsmr5-17 had hardly any inhibitory effect on the BF of IC1 isolates, but for IC2 and IC7 isolates, 31.25 µg/mL was sufficient. Our data show that the susceptibility of animal MDR-A. baumannii to AMPs most likely resembles that of human isolates, depending on their assignment to a particular IC. Even low concentrations of AMPs had a significant effect on BG. Therefore, AMPs represent a promising alternative in the treatment of MDR-A. baumannii, either as the sole therapy or in combination with antibiotics. Full article

The increasing emergence and dissemination of multidrug-resistant (MDR) bacterial pathogens have intensified the need for new antibiotics and alternative therapeutic strategies. Flavonoids, a diverse group of bioactive natural compounds found in plants, have shown significant promise as antibacterial agents. Flavonoids inhibit bacterial growth through various mechanisms, including disruption of cell wall synthesis, prevention of biofilm formation, disruption of cell membrane integrity, and inhibition of bacterial efflux pumps. These actions not only reduce bacterial viability but also enhance the efficacy of conventional antibiotics, offering a potential solution to antibiotic resistance. However, challenges such as poor bioavailability limit their clinical application. Recent advances in nanotechnology-based drug delivery systems, chemical modifications, and formulation techniques have shown promise in improving flavonoid bioavailability and therapeutic efficacy. This review evaluates the antibacterial mechanisms of flavonoids, explores their potential synergistic effects with antibiotics, and highlights strategies to overcome bioavailability issues. Our findings underscore the importance of continued research on flavonoids as promising candidates for innovative antibacterial therapies aimed at combating MDR bacterial infections. Full article

The rise of multidrug-resistant (MDR) bacteria in food products poses a significant threat to public health, necessitating innovative and sustainable antimicrobial solutions. This study investigates the green synthesis of zinc oxide nanoparticles (ZnO-NPs) using Stevia rebaudiana extracts to evaluate their antibacterial and antibiofilm activities against MDR Staphylococcus aureus strains isolated from sold fish samples. The obtained results show that the contamination with S. aureus reached 54.2% in the tested fish samples (n = 120), underscoring the urgent need for effective interventions. ZnO-NPs were successfully synthesized and characterized using UV-visible spectroscopy, FT-IR, XRD, and TEM, confirming their formation with an average size of 15.7 nm and reflecting their suitability for antimicrobial and biological applications. ZnO-NPs exhibited potent antibacterial activity, with a maximum inhibition zone of 24.4 ± 0.4 mm at 20 μg/disk, MIC values of 6.25–25 μg/mL, and MBC values of 12.5–50 μg/mL. Additionally, biofilm formation was inhibited by up to 92.1% at 250 μg/mL. Our mechanistic study confirmed that ZnO-NPs damage bacterial membranes and DNA, leading to the intracellular leakage of cell components that lead to bacterial cell lysis. The use of S. rebaudiana in ZnO-NP synthesis aligns with green chemistry principles, offering an eco-friendly alternative to conventional antibiotics and enhancing the bioactivity of ZnO-NPs, and may address the growing issue of antimicrobial resistance, thereby contributing to improved food safety and public health protection. Full article

Pseudomonas aeruginosa is one of world’s most threatening bacteria. In addition to the emerging prevalence of multi-drug resistant (MDR) strains, the bacterium also possesses a wide variety of virulence traits that worsen the course of the infections. Particularly, its ability to form biofilms that protect colonies from antimicrobial agents is a major cause of chronic and hard-to-treat infections in immune-compromised patients. This protective barrier also ensures cell growth on abiotic surfaces and thus enables bacterial survival on medical devices. Hence, as the WHO alerted to the need to develop new treatments, the use of anti-biofilm agents (ABAs) appeared as a promising approach. Given the selection pressure imposed by conventional antibiotics, a new therapeutic strategy has emerged that aims at reducing bacterial virulence without inhibiting cell growth. So-called anti-virulence agents (AVAs) would then restore the efficacy of conventional antibiotics (ATBs) or potentiate the effectiveness of the immune system. The last decade has seen the development of ABAs as AVAs against P. aeruginosa. This review aims to highlight the design strategy and critical features of these molecules to pave the way for further discoveries of highly potent compounds. Full article

Background: Thermophilic Campylobacter species are among the main culprits behind bacterial gastroenteritis globally and have grown progressively resistant to clinically important antimicrobials. Many studies have been carried out to explore innovative and alternative strategies to control antibiotic-resistant campylobacters in animal reservoirs and human hosts; however, limited studies have been performed to develop efficient control schemes against Campylobacter biofilms. Methods: This study investigated the antimicrobial and antibiofilm activities of some herbal extracts against multidrug-resistant (MDR) Campylobacter species recovered from different sources using phenotypic and molecular techniques. Results: The overall Campylobacter species prevalence was 21.5%, representing 15.25% and 6.25% for C. jejuni and C. coli, respectively. Regarding C. jejuni, the highest resistance rate was observed for amoxicillin–clavulanic acid and colistin (85.25% each), followed by cefotaxime (83.61%) and tetracycline (81.97%), whereas C. coli isolates showed absolute resistance to cefotaxime followed by erythromycin (92%) and colistin (88%). Remarkably, all Campylobacter isolates were MDR with elevated multiple antimicrobial resistance (MAR) indices (0.54–1). The antimicrobial potentials of green tea (Camellia sinensis), rosemary (Rosmarinus officinalis) and ginger (Zingiber officinale) extracts against MDR Campylobacter isolates were assessed by the disk diffusion assay and broth microdilution technique. Green tea extract showed a marked inhibitory effect against tested isolates, exhibiting growth inhibition zone diameters of 8 to 38 mm and a minimum inhibitory concentration (MIC) range of 1.56–3.12 mg/mL, unlike the rosemary and ginger extracts. Our findings reveal a respectable antibiofilm activity (>50% biofilm formation inhibition) of green tea against the preformed biofilms of Campylobacter isolates. Furthermore, real-time quantitative polymerase chain reaction (RT-qPCR) results showed a significant decrease (p < 0.05) in the expression levels of biofilm biosynthesis gene and its regulator (FlaA and LuxS, respectively) in Campylobacter isolates treated with the green tea extract in comparison with untreated ones. Conclusion: This is the first in vitro approach that has documented the inhibitory activity of green tea extract against MDR-biofilm-producing Campylobacter species isolated from different sources. Further in vivo studies in animals’ models should be performed to provide evidence of concept for the implementation of this alternative candidate for the mitigation of MDR Campylobacter infections in the future. Full article

Staphylococcus pseudintermedius (SP) is a commensal and opportunistic pathogen of skin and mucosal surfaces, isolated from healthy dogs and from canine pyoderma cases. It has recently gained attention due to its increasing antibiotic resistance. Platelet-rich plasma (PRP) is a biological product, obtained through a blood centrifugation process, which has antibacterial properties evidenced by in vitro and in vivo studies conducted in both the human and veterinary field. This in vitro study evaluated the antimicrobial effect of canine non-activated and activated leucocyte-rich PRP (L-PRP) and platelet-poor plasma (PPP) against two strains of SP isolated from dogs with pyoderma: one a multidrug-resistant strain (MDR) and one a non-MDR strain. Twenty healthy un-sedated adult blood donor dogs were enrolled for L-PRP and PPP production via a closed semi-automatic system for veterinary use. The evaluation of antimicrobial effect was performed using the micro-inhibition in broth method, exposing SP strains to 10 L-PRP, 10 activated L-PRP and 10 PPP samples, respectively. Bacterial growth was evaluated using CFU count at three timepoints (immediately after incubation T0, after 1 h T1 and after 2 h T2). L-PRP and PPP had a significant antimicrobial effect at all three timepoints which was similar against both non-MDR and MDR SP strains. Activation appeared to reduce the duration of the antimicrobial effect in L-PRP. More studies are necessary to confirm these preliminary results. Full article

In response to the escalating crisis of antimicrobial resistance (AMR), there is an urgent need to research and develop novel antibiotics. This study presents the synthesis and assessment of innovative 4-aminoquinoline-benzohydrazide-based molecular hybrids bearing aryl aldehydes (HD1-23) and substituted isatin warheads (HS1-12), characterized using multispectroscopic techniques with high purity confirmed by HRMS. The compounds were evaluated against a panel of clinically relevant antibacterial strains including the Gram-positive Enterococcus faecium, Bacillus subtilis, and Staphylococcus aureus and a Gram-negative Pseudomonas aeruginosa bacterial strain. Preliminary screenings revealed that several test compounds had significant antimicrobial effects, with HD6 standing out as a promising compound. Additionally, HD6 demonstrated impressively low minimum inhibitory concentrations (MICs) in the range of (8–128 μg/mL) against the strains B. subtilis, S. aureus and P. aeruginosa. Upon further confirmation, HD6 not only showed bactericidal properties with low minimum bactericidal concentrations (MBCs) such as (8 μg/mL against B. subtilis) but also displayed a synergistic effect when combined with the standard drug ciprofloxacin (CIP), highlighted by its FICI value of (0.375) against P. aeruginosa, while posing low toxicity risk. Remarkably, HD6 also inhibited a multidrug-resistant (MDR) bacterial strain, marking it as a critical addition to our antimicrobial arsenal. Computation studies were performed to investigate the possible mechanism of action of the most potent hybrid HD6 on biofilm-causing protein (PDB ID: 7C7U). The findings suggested that HD6 exhibits favorable binding free energy, which is supported by the MD simulation studies, presumably responsible for the bacterial growth inhibition. Overall, this study provides a suitable core for further synthetic alterations for their optimization as an antibacterial agent. Full article

The increasing prevalence of multidrug-resistant (MDR) pathogens, persistent biofilms, oxidative stress, and cancerous cell proliferation poses significant challenges in healthcare and environmental settings, highlighting the urgent need for innovative and sustainable therapeutic solutions. The exploration of nanotechnology, particularly the use of green-synthesized nanoparticles, offers a promising avenue to address these complex biological challenges due to their multifunctional properties and biocompatibility. Utilizing a green synthesis approach, Mauritia flexuosa Mf-Ag₂ONPs were synthesized and characterized using dynamic light scattering (DLS), transmission electron microscopy (TEM), X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy coupled with scanning electron microscopy (EDS-SEM), UV-Vis spectroscopy, and Fourier transform infrared spectroscopy (FTIR). The Mf-Ag₂ONPs exhibited potent antibacterial effects against both non-resistant and MDR bacterial strains, with minimum inhibitory concentrations (MICs) ranging from 11.25 to 45 µg/mL. Mf-Ag₂ONPs also demonstrated significant antifungal efficacy, particularly against Candida glabrata, with an MIC of 5.63 µg/mL. Moreover, the nanoparticles showed strong biofilm inhibition capabilities and substantial antioxidant properties, underscoring their potential to combat oxidative stress. Additionally, Mf-Ag₂ONPs exhibited pronounced anticancer properties against various cancer cell lines, displaying low IC₅₀ values across various cancer cell lines while maintaining minimal hemolytic activity at therapeutic concentrations. These findings suggest that Mf-Ag₂ONPs synthesized via an eco-friendly approach offer a promising alternative for biomedical applications, including antimicrobial, antifungal, antioxidant, and anticancer therapies, warranting further in vivo studies to fully exploit their therapeutic potential. Full article