Increased antimicrobial resistance requires effective ways to overcome the global challenge of bacterial infections, including methicillin-resistant Staphylococcus aureus (MRSA). From the emergence of MRSA to its continued evolution, it is important to explore this pathogen from fresh perspectives and develop corresponding coping strategies to counter its growing threat. New coping strategies are continuously emerging, including but not limited to enhancing penetration capabilities or targeting their virulence. This review summarizes the epidemiological characteristics, drug resistance mechanisms, and therapeutic strategies of MRSA that have emerged over the past fifteen years. The focus of this paper is to explore the promising applications and current limitations of novel MRSA control strategies. This review serves as a key resource for treating MRSA infections and discussing novel strategies to overcome bacterial drug resistance.
Piceatannol (PIC) is a natural stilbene extracted from grape skins that exhibits biological activities such as antibacterial, antitumor, and antioxidant activities. The present study was carried out to further investigate the effect of PIC on the antibacterial activity of different antibiotics and to reveal the antibacterial mechanism of PIC. We found that PIC had an inhibitory effect against Staphylococcus aureus (S. aureus); its minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were 128 μg/mL and 256 μg/ mL, respectively. Additionally, we measured the fractional inhibitory concentration (FIC) of PIC combined with antibiotics via the checkerboard method. The results showed that when PIC and ciprofloxacin (CIP) were combined, they displayed a synergistic effect against S. aureus. Moreover, this synergistic effect was verified by time–kill assays. Further, the results of the membrane permeability assay and proton motive force assay revealed that PIC could enhance the sensitivity of S. aureus to CIP by dissipating the bacterial proton motive force (PMF), particularly the ∆ψ component, rather than increasing membrane permeability. PIC also inhibited bacterial adenosine triphosphate (ATP) synthesis and was less likely to induce bacterial resistance but exhibited slight hemolytic activity on mammalian erythrocytes. In summary, the combination of PIC and CIP is expected to become a new drug combination to combat S. aureus.
The aim of this study was to determine the prevalence and association of EGUS in horses of different ages, breeds and occupations. Gastroscopies were performed on 395 horses, and gastric ulcers were graded on a scoring system from 0 to 4. The relationship between age, breed, and work, along with the prevalence of gastric ulcers and their influences, were evaluated. The prevalence rate of ulcers in this herd was 78%. Older horses were prone to ulcers in both the glandular and squamous mucosal areas. Across the different jobs surveyed, 60% of the horses had a score of 2 or above. For the horses participating in more intense jobs (group performances, pulling carts, etc.), the number of horses with an ulcer score of 2 or above exceeded 50% of the total number of horses in this job. The prevalence of gastric ulcers was high, and these ulcers were severe in the horses belonging to the examined club, with no association between age or breed and the prevalence of ulcers; however, there was a difference in the location of the ulcers between breeds, as well as differences in the incidence and severity of ulcers depending on work activity. This study provides data reference values for the control and prevention of gastric ulcers in horses in this horse farm.
Host genetics and environmental factors can both shaping composition of gut microbiota, yet which factors are more important is still under debating. Yak ( Bos grunniens ) and Tibetan sheep ( Ovis aries ) are very different from the size and genetics. Nomadic Tibetan people keep them as main livestock and feeding them with same grazing systems, which provide a good opportunity to study the effects of diet and host species on gut microbiome. We collected fecal samples from yaks and Tibetan sheeps at different seasons when they were feed with different diets. Illumina data showed that major bacterial phyla of both animals are Bacteroidetes and Firmicutes, which agree with the previous reports. And the season effect had a higher impact on the gut microbiota than that of host species, though the animals are taxonomically distinguished each other at subfamily level. Since that the animal grazing differently at different seasons, this study indicated that diet can trump the host genetics even at higher taxonomic level. This finding provides a cautionary note for the researchers to link host genetics to the composition and function of the gut microbiota. Importance: Yak and Tibetan sheep are very different from the size and genetics (from different sub-family). Nomadic Tibetan people keep them as main livestock and feeding them with same grazing systems, which provide a good opportunity to study the effects of diet and host species on the gut microbiota. Results indicated that diet can trump the host genetics even at higher taxonomic level. This finding provides a cautionary note for the researchers to link host genetics to the composition and function of the gut microbiota.
This study aimed to establish a more sensitive and reliable quantitative method for determining rafoxanide (RFX) in ovine plasma. The method was applied in an 84-day long-term comparative pharmacokinetic trial to evaluate the performance of a rafoxanide nanosuspension (RFX-NS) versus its conventional suspension (RFX-S) in sheep. Characterization of the two formulations revealed the following results: RFX-NS had an average particle size of 484.93 ± 43.11 nm, a uniform size distribution (PDI 0.06 ± 0.07), and a Zeta potential of −43.59 ± 0.67 mV, which were significantly superior to those of RFX-S (particle size 2379.67 ± 121.71 nm, PDI 0.93 ± 0.10, Zeta potential −38.10 ± 0.55 mV), demonstrating excellent physical stability. In vitro dissolution tests indicated a higher dissolution rate for RFX-NS (97.6% at 60 min). By integrating formulation characterization, in vitro dissolution assessment, and pharmacokinetic studies, this research provided a comprehensive analysis of the differences between the two formulations. Pharmacokinetic results showed that, compared to RFX-S, RFX-NS had a significantly reduced apparent volume of distribution (Vz/F: 856.02 ± 274.00 vs. 1404.17 ± 285.1 mL/kg, p < 0.01), a shorter elimination half-life (t1/2: 4.05 ± 1.18 vs. 5.32 ± 0.94 days, p < 0.05), and a relative bioavailability of 128.98%. These findings suggest that RFX-NS is an improved novel formulation superior to the conventional suspension, as it enhances drug efficacy and efficiency by improving drug dissolution and absorption.