Therapeutic Potential of Mangosteen Pericarp Extract-Loaded Liposomes against Superficial Skin Infection Caused by Staphylococcus pseudintermedius in a Murine Model.

α-mangostin (α-MG) demonstrates antibacterial activity against Staphylococcus species. Therefore, this study aimed to explore the antibacterial activity of α-MG-rich mangosteen pericarp extract (MPE)-loaded liposomes against Staphylococcus isolates from companion animal skin diseases in vitro and evaluated their therapeutic potential in a murine model of superficial skin infection caused by S. pseudintermedius. α-MG-rich extract was purified from mangosteen pericarp and then complexed with γ-cyclodextrin (γ-CD), forming the inclusion complexes. Nanoliposomes containing MPE and γ-CD complexes were prepared by adding lecithin and casein. Minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of MPE-loaded liposomes were determined using agar dilution and broth microdilution methods. The therapeutic potential of MPE-loaded liposomes was evaluated in vivo on tape-stripped skin lesions infected with S. pseudintermedius. Purified MPE and MPE-loaded liposomes contained 402.43 mg/g and 18.18 mg/g α-MG, respectively. MPE-loaded liposomes showed antibacterial activity against clinical Staphylococcus isolates in vitro but did not show antibacterial activity against Gram-negative bacterial isolates. MPE-loaded liposomes demonstrated consistent MICs and MBCs against Staphylococcus isolates. These liposomes significantly reduced bacterial numbers and lesional sizes in a superficial skin infection model. Moreover, they reconstructed the epidermal barrier in skin lesions. The therapeutic concentrations of MPE-loaded liposomes did not induce cytotoxicity in canine progenitor epidermal keratinocyte cells. In conclusion, MPE-loaded liposomes hold promise for the development of a prospective topical formulation to treat superficial pyoderma in companion animals.

PmrAB controls virulence-associated traits and outer membrane vesicle biogenesis in Acinetobacter baumannii.

The PmrAB two-component system modulates colistin resistance in Acinetobacter baumannii, but its association with the virulence traits of this bacterium remains uncharacterized. This study explored the role of A. baumannii PmrAB in surface motility, biofilm formation, and outer membrane vesicle (OMV) biogenesis using wild-type (WT) A. baumannii 17978 and ΔpmrA and ΔpmrB mutant strains. The two mutant strains exhibited significantly decreased surface motility compared with that of WT strain by the low expression of abaI, abaR, A1S_0113, A1S_0115, and A1S_0116. Biofilm mass also significantly decreased in the two mutant strains at 12 h of incubation, but restored at 24 h. Under static culture conditions for 12 h, the two mutant strains showed low pgaA expression. However, the other biofilm-associated genes, such as csuC, csuE, ompA, and bap, showed different expression between the two mutant strains. Although the size of OMVs was similar among the three strains, the number of OMVs secreted from the two mutant strains slightly decreased compared with that secreted from the WT strain. Protein concentrations in the OMVs of ΔpmrA mutant significantly decreased compared with those in the OMVs of WT and ΔpmrB strains. Overall, PmrAB modulates virulence traits and OMV biogenesis in A. baumannii.

Antimicrobial activity of α-mangostin against Staphylococcus species from companion animals in vitro and therapeutic potential of α-mangostin in skin diseases caused by S. pseudintermedius.

Antimicrobial resistance in Staphylococcus species from companion animals is becoming increasingly prevalent worldwide. S. pseudintermedius is a leading cause of skin infections in companion animals. α-mangostin (α-MG) exhibits various pharmacological activities, including antimicrobial activity against G (+) bacteria. This study investigated the antimicrobial activity of α-MG against clinical isolates of Staphylococcus species from companion animals and assessed the therapeutic potential of α-MG in skin diseases induced by S. pseudintermedius in a murine model. Furthermore, the action mechanisms of α-MG against S. pseudintermedius were investigated. α-MG exhibited antimicrobial activity against clinical isolates of five different Staphylococcus species from skin diseases of companion animals in vitro, but not G (-) bacteria. α-MG specifically interacted with the major histocompatibility complex II analogous protein (MAP) domain-containing protein located in the cytoplasmic membrane of S. pseudintermedius via hydroxyl groups at C-3 and C-6. Pretreatment of S. pseudintermedius with anti-MAP domain-containing protein polyclonal serum significantly reduced the antimicrobial activity of α-MG. The sub-minimum inhibitory concentration of α-MG differentially regulated 194 genes, especially metabolic pathway and virulence determinants, in S. pseudintermedius. α-MG in pluronic lecithin organogel significantly reduced the bacterial number, partially restored the epidermal barrier, and suppressed the expression of cytokine genes associated with pro-inflammatory, Th1, Th2, and Th17 in skin lesions induced by S. pseudintermedius in a murine model. Thus, α-MG is a potential therapeutic candidate for treating skin diseases caused by Staphylococcus species in companion animals.

Acinetobacter baumannii under Acidic Conditions Induces Colistin Resistance through PmrAB Activation and Lipid A Modification.

Colistin is a last-resort antimicrobial agent for treating carbapenem-resistant Acinetobacter baumannii infections. The activation of PmrAB by several environmental signals induces colistin resistance in Gram-negative bacteria. This study investigated the molecular mechanisms of colistin resistance in A. baumannii under acidic conditions using wild-type (WT) A. baumannii 17978, ΔpmrA and ΔpmrB mutants, and pmrA-complemented strains. The pmrA or pmrB deletion did not affect the growth of A. baumannii under acidic or aerobic conditions. A. baumannii under acidic (pH 5.5) and high-iron (1 mM) conditions showed 32- and 8-fold increases in the minimum inhibitory concentrations (MICs) of colistin, respectively. The ΔpmrA and ΔpmrB mutants at pH 5.5 showed a significant decrease in colistin MICs compared to the WT strain at pH 5.5. No difference in colistin MICs was observed between WT and mutant strains under high-iron conditions. The pmrCAB expression significantly increased in the WT strain at pH 5.5 compared to the WT strain at pH 7.0. The pmrC expression significantly decreased in two mutant strains at pH 5.5 compared to the WT strain at pH 5.5. The PmrA protein was expressed in the ΔpmrA strain carrying ppmrA_FLAG plasmids at pH 5.5 but not at pH 7.0. Lipid A modification by the addition of phosphoethanolamine was observed in the WT strain at pH 5.5. In conclusion, this study demonstrated that A. baumannii under acidic conditions induces colistin resistance via the activation of pmrCAB operon and subsequent lipid A modification.

Disaster-Related Injury Management: High Prevalence of Wound Infection After Super Typhoon Haiyan.

BACKGROUND: After Super Typhoon Haiyan, a category 5 tropical cyclone, insufficient resources were available for medical management. Many patients in the Philippines were wounded as a result of the disaster. We examined the prevalence, risk factors, and consequences of disaster-related wounds and wound infection in the post-disaster period. METHODS: We performed a retrospective review of consecutive patients admitted to a Korean Disaster Relief Team clinic at St. Paul's Hospital, Tacloban City, Republic of Philippines, between December 9 and 13, 2013. Traumatic injury patients were included; patients not exhibiting a wound were excluded. RESULTS: Of the 160 patients enrolled in the study, 71 (44.4%) had infected wounds. There were no significant differences in the age, sex, past medical history, wound site, wound depth, injury mechanism, or inducer of injury between the uninfected and infected groups. In the univariate analysis, a foreign-body-contaminated wound, a chronic wound, elapsed time from injury to medical contact, an inadequately cared for wound, and need for subsequent wound management were associated with wound infection (P<0.05). The multivariate analysis revealed that foreign body contamination and having an inadequately cared for wound were associated with wound infection (odds ratio [OR]: 10.12, 95% confidence interval [CI]: 3.59-28.56; OR: 3.51, 95% CI: 1.07-11.51, respectively). CONCLUSION: In the post-disaster situation, many wound infections required definitive care. Wound infection was associated with inadequately cared for wounds and foreign-body-contaminated wounds.