Design of biodegradable polyurethanes and post-modification with long alkyl chains via inhibiting biofilm formation and killing drug-resistant bacteria for the treatment of wound bacterial infection.

The development of cationic polymers that simulate antimicrobial peptides to treat bacterial infections has received much research interest. In order to obtain polymers that can not only eradicate bacteria but also inhibit biofilm formation, without inducing bacterial drug resistance, a series of cationic polymers have been developed. Despite recent progress, the chemical structures of these polymers are stable, making them recalcitrant to biodegradation and metabolism within organisms, potentially inducing long-term toxicity. To overcome this limitation, herein, a novel strategy of designing biodegradable polyurethanes with tertiary amines and quaternary ammonium salts via condensation polymerization and post-functionalizing them is reported. These polymers were found to exhibit potent antibacterial activity against Staphylococcus aureus and Escherichia coli, effectively prevent the formation of Staphylococcus aureus biofilms, act quickly and effectively against bacteria and display no resistance after repeated use. In addition, the potent in vivo antibacterial effects of these antimicrobial polyurethanes in a mouse model with methicillin-resistant Staphylococcus aureus skin infection are demonstrated.

Flourishing Antibacterial Strategies for Osteomyelitis Therapy.

Osteomyelitis is a destructive disease of bone tissue caused by infection with pathogenic microorganisms. Because of the complex and long-term abnormal conditions, osteomyelitis is one of the refractory diseases in orthopedics. Currently, anti-infective therapy is the primary modality for osteomyelitis therapy in addition to thorough surgical debridement. However, bacterial resistance has gradually reduced the benefits of traditional antibiotics, and the development of advanced antibacterial agents has received growing attention. This review introduces the main targets of antibacterial agents for treating osteomyelitis, including bacterial cell wall, cell membrane, intracellular macromolecules, and bacterial energy metabolism, focuses on their mechanisms, and predicts prospects for clinical applications.

Resistance of poliovirus 1 and enterovirus A71 against alcohol and other disinfectants.

Poliovirus 1 (PV 1) is the standard virus used in tests to support claims of virucidal property in commercial hand sanitizers and disinfectants in China. Classified within the same genus as poliovirus, enterovirus A71 (EV A71), which causes hand-foot-mouth disease among children, has caused numerous outbreaks in China and other countries. Hand hygiene and surface cleaning are critical to prevent and control this disease and many other infectious diseases. This study compared the efficacies of 17 self-made alcohol-based hand sanitizers and 10 commercially available disinfectants (4 high-level, 4 intermediate-level, 2 low-level) against these two viruses. The results showed that by itself, ethanol needed to reach a concentration of 75 % to meet the inactivation requirement of 4-log reduction in average TCID50 against PV 1. Nine out of 13 laboratory-formulated alcohol-based hand sanitizers reached the 4-log inactivation requirement against PV 1 after 4.5 min, while the remaining four sanitizers did not. Unexpectedly, none of the tested ethanol-based sanitizers inactivated EV A71 by 4-log. For the commercially available disinfectants, all four high-level and one intermediate-level disinfectants passed the inactivation requirements against both PV 1 and EV A71, while two intermediate-level disinfectants met the inactivation requirement against PV 1 but failed against EV A71. The last intermediate-level and both low-level disinfectants did not meet the requirement for either PV 1 or EV A71. Therefore, PV 1 is more susceptible to inactivation by many common alcohol-based and non-alcohol-based disinfectants than EV A71. Therefore, the adoption of EV A71 as the standard test virus would elevate the disinfectant requirement standard and provide better protection for the public. Based on these results, seven new alcohol-based hand sanitizer recipes were formulated and found to be effective against both PV 1 and EV A71, with two candidates reaching the required 4-log virus reduction efficacy within 1 min.

Surface micropattern reduces colonization and medical device-associated infections.

PURPOSE: Surface microtopography offers a promising approach for infection control. The goal of this study was to provide evidence that micropatterned surfaces significantly reduce the potential risk of medical device-associated infections. METHODOLOGY: Micropatterned and smooth surfaces were challenged in vitro against the colonization and transference of two representative bacterial pathogens - Staphylococcus aureus and Pseudomonas aeruginosa. A percutaneous rat model was used to assess the effectiveness of the micropattern against device-associated S. aureus infections. After the percutaneous insertion of silicone rods into (healthy or immunocompromised) rats, their backs were inoculated with S. aureus. The bacterial burdens were determined in tissues under the rods and in the spleens. RESULTS: The micropatterns reduced adherence by S. aureus (92.3 and 90.5 % reduction for flat and cylindrical surfaces, respectively), while P. aeruginosa colonization was limited by 99.9 % (flat) and 95.5 % (cylindrical). The micropatterned surfaces restricted transference by 95.1 % for S. aureus and 94.9 % for P. aeruginosa, compared to smooth surfaces. Rats with micropatterned devices had substantially fewer S. aureus in subcutaneous tissues (91 %) and spleens (88 %) compared to those with smooth ones. In a follow-up study, immunocompromised rats with micropatterned devices had significantly lower bacterial burdens on devices (99.5 and 99.9 % reduction on external and internal segments, respectively), as well as in subcutaneous tissues (97.8 %) and spleens (90.7 %) compared to those with smooth devices. CONCLUSION: Micropatterned surfaces exhibited significantly reduced colonization and transference in vitro, as well as lower bacterial burdens in animal models. These results indicate that introducing this micropattern onto surfaces has high potential to reduce medical device-associated infections.

Involvement of hippocampal phosphatidylethanolamine-binding protein in morphine dependence and withdrawal.

Drug addiction is thought to result from an intractable and aberrant learning and memory in response to drug-related stimulation, and cholinergic neurotransmission plays an important role in this process. Phosphatidylethanolamine-binding protein (PEBP) is the precursor of the hippocampal cholinergic neurostimulating peptide (HCNP), an 11 amino acid peptide that enhances the production of choline acetyltransferase (ChAT) and assists in the development of cholinergic projections from the medial septal nuclei to the hippocampus. However, whether PEBP is involved in drug addiction remains unclear. In the present study, PEBP expression in the hippocampus, as detected by proteomics analysis, was found to be dramatically up-regulated after rats received chronic morphine treatment. Western blotting analysis revealed a specific up-regulation of PEBP expression in the hippocampus but not in any other brain regions assessed. A down-regulation of hippocampal PEBP levels induced by antisense oligodeoxynucleotides resulted in aggravated morphine dependence. Together, these findings indicate that PEBP is involved in morphine dependence. Moreover, the time course of PEBP expression changes and ChAT activity was investigated during chronic morphine treatment and withdrawal. The results showed that the hippocampal PEBP levels were up-regulated during chronic morphine treatment and returned to the baseline 3 days after withdrawal, after which PEBP levels were persistently up-regulated for 28 days after withdrawal. The changes in hippocampal ChAT activity followed a pattern that was similar to that of the PEBP levels. Taken together, these results suggest that hippocampal PEBP is involved in morphine dependence and withdrawal, perhaps through modulating cholinergic transmission in the hippocampus.