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Jatrorrhizine suppresses the antimicrobial resistance of methicillin-resistant Staphylococcus aureus.

ABSTRACT: Bacterial resistance to antimicrobial agents, including multidrug resistance, is an increasing problem in the treatment of infectious diseases. The development of resistance-modifying agents represents a potential strategy to alleviate the spread of bacterial resistance to antibiotics. A checkerboard microdilution assay was used to determine the synergy of jatrorrhizine and the antibiotic, norfloxacin (NFX). A bacterial ethidium bromide efflux assay, reverse transcription semi-quantitative polymerase chain reaction analysis and molecular docking study were performed. The three-dimensional structure of NorA multidrug efflux pump (NorA) was generated using a multiple threading approach. A murine thigh infection model was used to evaluate the in vivo synergistic effect. As a natural product, jatrorrhizine exhibited little antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) SA1199B with a minimum inhibitory concentration (MIC) of 64 mg/l. According to the investigations of the mechanism, jatrorrhizine significantly inhibited bacterial drug efflux and the expression of NorA in the mRNA level as it can bind to NorA by hydrogen-bonds, hydrophobic and electrostatic interactions. The in vivo synergistical bactericidal activity of jatrorrhizine and NFX against MRSA was confirmed in a murine thigh infection model. As a novel resistance-modifying agent, jatrorrhizine exhibited in vitro and in vivo synergistic activities against MRSA, and inhibited bacterial drug efflux. The effects were mediated by the suppression of NorA mRNA expression and/or interactions with NorA efflux pump. These data support the hypothesis that jatrorrhizine is a potential agent for therapeutic use in infections caused by MRSA.

SUBMITTER: Yu H

PROVIDER: S-EPMC6781805 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Jatrorrhizine suppresses the antimicrobial resistance of methicillin-resistant <i>Staphylococcus aureus</i>.

Yu Haiming H Wang Yuefei Y Wang Xiaoqing X Guo Junjie J Wang Hui H Zhang Hao H Du Fengxia F

Experimental and therapeutic medicine 20190923 5

Bacterial resistance to antimicrobial agents, including multidrug resistance, is an increasing problem in the treatment of infectious diseases. The development of resistance-modifying agents represents a potential strategy to alleviate the spread of bacterial resistance to antibiotics. A checkerboard microdilution assay was used to determine the synergy of jatrorrhizine and the antibiotic, norfloxacin (NFX). A bacterial ethidium bromide efflux assay, reverse transcription semi-quantitative polym ...[more]

PMID: 31616505

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Project description:BackgroundColonization by livestock-associated MRSA (LA-MRSA) has increasingly been reported in the swine population worldwide. The aim of this study was to assess the prevalence of MRSA nasal carriage in healthy pigs, including the black (Calabrese) breed, from farms in the Calabria Region (Southern Italy). Between January and March 2018, a total of 475 healthy pigs reared in 32 farms were sampled by nasal swabbing. MRSA isolates were characterized by spa, MLST and SCCmec typing, and susceptibility testing to 17 antimicrobials.Results22 of 32 (66.8%) pig farms resulted positive for MRSA. The prevalence of MRSA was 46.1% (219 MRSA culture-positive out of 475 samples). MRSA colonization was significantly higher in intensive farms and in pigs with a recent or ongoing antimicrobial treatment. All 219 MRSA isolates were assigned to ST398. The most common spa types were t011 (37.0%), t034 (22.4%) and t899 (15.1%). A novel spa type (t18290) was detected in one isolate. An insertion of IS256 in the ST398-specific A07 fragment of the SAPIG2195 gene was detected in 10 out of 81 t011 isolates. Nearly all isolates carried the SCCmec type V element, except 11 isolates that carried the SCCmec type IVc. None of the isolates was positive for the Panton-Valentine leukocidin. All isolates were resistant to tetracycline. High resistance rates were also found for clindamycin (93.1%), trimethoprim/sulfamethoxazole (68.4%), fluoroquinolones (47.9-65.3%) and erythromycin (46.1%). None of the isolates was resistant to vancomycin and fusidic acid. Overall, a multidrug resistant phenotype was observed in 88.6% of isolates.ConclusionsWe report a high prevalence of MRSA among healthy swine in Southern Italy farms, with higher isolation frequency associated with intensive farming. The epidemiological types identified in our study reflect those reported in other European countries. Our findings underscore the importance of monitoring the evolution of LA-MRSA in pig farms in order to implement control measures and reduce the risk of spread in the animal population.

Project description:The chemotherapeutic options for methicillin-resistant Staphylococcus aureus (MRSA) infections are limited. Due to the multiple resistant MRSA, therapeutic failure has occurred frequently, even using antibiotics belonging to different categories in clinical scenarios, very recently. This study aimed to investigate the interactions between 11 antibiotics representing different mechanisms of action against MRSA strains and provide therapeutic strategies for clinical infections. Susceptibilities for MRSA strains were determined by broth microdilution or agar dilution according to CLSI guideline. By grouping with each other, a total of 55 combinations were evaluated. The potential synergism was detected through drug interaction assays and further investigated for time-killing curves and an in vivo neutropenic mouse infection model. A total of six combinations (vancomycin with rifampicin, vancomycin with oxacillin, levofloxacin with oxacillin, gentamycin with oxacillin, clindamycin with oxacillin, and clindamycin with levofloxacin) showed synergistic activity against the MRSA ATCC 43300 strain. However, antibacterial activity against clinical isolate #161402 was only observed when vancomycin combined with oxacillin or rifampicin in time-killing assays. Next, therapeutic effectiveness of vancomycin/oxacillin and vancomycin/rifampicin was verified by an in vivo mouse infection model inoculated with #161402. Further investigations on antimicrobial synergism of vancomycin plus oxacillin and vancomycin plus rifampicin against 113 wild-type MRSA strains were evidenced by combined antibiotic MICs and bacterial growth inhibition and in vitro dynamic killing profiles. In summary, vancomycin/rifampicin and vancomycin/oxacillin are the most potential combinations for clinical MRSA infection upon both in vitro and in vivo tests. Other synergetic combinations of levofloxacin/oxacillin, gentamycin/oxacillin, clindamycin/oxacillin, and clindamycin/fosfomycin are also selected but may need more assessment for further application.

Project description:BackgroundThe emergence of methicillin-resistant Staphylococcus aureus (MRSA) has increased and poses a significant threat to human and animal health in Cameroon and the world at large. MRSA strains have infiltrated various settings, including hospitals, communities, and livestock, contributing to increased morbidity, treatment costs, and mortality. This evidence synthesis aims to understand MRSA prevalence, resistance patterns, and genetic characterization in Cameroon.MethodsThe methodology was consistent with the PRISMA 2020 guidelines. Studies of any design containing scientific data on MRSA prevalence, genetic diversity, and antimicrobial resistance patterns in Cameroon were eligible for inclusion, with no restrictions on language or publication date. The search involved a comprehensive search strategy in several databases including Medline, Embase, Global Health, Web of Science, African Index Medicus, and African Journal Online. The risk of bias in the included studies was assessed using the Hoy et al tool, and the results were synthesized and presented in narrative synthesis and/or tables and graphs.ResultsThe systematic review analyzed 24 studies, mostly conducted after 2010, in various settings in Cameroon. The studies, characterized by moderate to low bias, revealed a wide prevalence of MRSA ranging from 1.9% to 46.8%, with considerable variation based on demographic and environmental factors. Animal (0.2%), food (3.2% to 15.4%), and environmental samples (0.0% to 34.6%) also showed a varied prevalence of MRSA. The genetic diversity of MRSA was heterogeneous, with different virulence gene profiles and clonal lineages identified in various populations and sample types. Antimicrobial resistance rates showed great variability in the different regions of Cameroon, with notable antibiotic resistance recorded for the beta-lactam, fluoroquinolone, glycopeptide, lincosamide, and macrolide families.ConclusionThis study highlights the significant variability in MRSA prevalence, genetic diversity, and antimicrobial resistance patterns in Cameroon, and emphasizes the pressing need for comprehensive antimicrobial stewardship strategies in the country.

Dataset Information

Jatrorrhizine suppresses the antimicrobial resistance of methicillin-resistant Staphylococcus aureus.

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Jatrorrhizine suppresses the antimicrobial resistance of methicillin-resistant <i>Staphylococcus aureus</i>.

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