scholarly journals Andrographolide Sulfonate Is a Promising Treatment to Combat Methicillin-resistant Staphylococcus aureus and Its Biofilms

2021 ◽  
Vol 12 ◽  
Author(s):  
Lulu Zhang ◽  
Bo Wen ◽  
Mei Bao ◽  
Yungchi Cheng ◽  
Tariq Mahmood ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Health And Safety ◽  
Sebacic Acid ◽  
Inhibitory Effect ◽  
Morphological Observation ◽  
Methicillin Resistant ◽  
Expression Of Genes ◽  
Mrsa Infection ◽  
Underlying Mechanisms

Methicillin-resistant Staphylococcus aureus (MRSA) is a drug-resistant pathogen threatening human health and safety. Biofilms are an important cause of its drug resistance and pathogenicity. Inhibition and elimination of biofilms is an important strategy for the treatment of MRSA infection. Andrographolide sulfonate (AS) is an active component of the traditional herbal medicine Andrographis paniculata. This study aims to explore the inhibitory effect and corresponding mechanisms of AS on MRSA and its biofilms. Three doses of AS (6.25, 12.5, and 25 mg/ml) were introduced to MRSA with biofilms. In vitro antibacterial testing and morphological observation were used to confirm the inhibitory effect of AS on MRSA with biofilms. Real-time PCR and metabonomics were used to explore the underlying mechanisms of the effect by studying the expression of biofilm-related genes and endogenous metabolites. AS displayed significant anti-MRSA activity, and its minimum inhibitory concentration was 50 μg/ml. Also, AS inhibited biofilms and improved biofilm permeability. The mechanisms are mediated by the inhibition of the expression of genes, such as quorum sensing system regulatory genes (agrD and sarA), microbial surface components–recognizing adhesion matrix genes (clfA and fnbB), intercellular adhesion genes (icaA, icaD, and PIA), and a gene related to cellular eDNA release (cidA), and the downregulation of five biofilm-related metabolites, including anthranilic acid, D-lactic acid, kynurenine, L-homocitrulline, and sebacic acid. This study provided valuable evidence for the activity of AS against MRSA and its biofilms and extended the methods to combat MRSA infection.

scholarly journals In VitroPharmacodynamics of Human Simulated Exposures of Ceftaroline and Daptomycin against MRSA, hVISA, and VISA with and without Prior Vancomycin Exposure

2013 ◽  
Vol 58 (2) ◽  
pp. 672-677 ◽  
Author(s):  
Amira A. Bhalodi ◽  
Mao Hagihara ◽  
David P. Nicolau ◽  
Joseph L. Kuti
Keyword(s):  
Staphylococcus Aureus ◽  
Body Weight ◽  
Sequential Therapy ◽  
Free Drug ◽  
Pharmacodynamic Model ◽  
Prior Exposure ◽  
Methicillin Resistant ◽  
Content Type ◽  
Mrsa Infection

ABSTRACTThe effects of prior vancomycin exposure on ceftaroline and daptomycin therapy against methicillin-resistantStaphylococcus aureus(MRSA) have not been widely studied. Humanized free-drug exposures of vancomycin at 1 g every 12 h (q12h), ceftaroline at 600 mg q12h, and daptomycin at 10 mg/kg of body weight q24h were simulated in a 96-hin vitropharmacodynamic model against three MRSA isolates, including one heteroresistant vancomycin-intermediateS. aureus(hVISA) isolate and one VISA isolate. A total of five regimens were tested: vancomycin, ceftaroline, and daptomycin alone for the entire 96 h, and then sequential therapy with vancomycin for 48 h followed by ceftaroline or daptomycin for 48 h. Microbiological responses were measured by the changes in log10CFU during 96 h from baseline. Control isolates grew to 9.16 ± 0.32, 9.13 ± 0.14, and 8.69 ± 0.28 log10CFU for MRSA, hVISA, and VISA, respectively. Vancomycin initially achieved ≥3 log10CFU reductions against the MRSA and hVISA isolates, followed by regrowth beginning at 48 h; minimal activity was observed against VISA. The change in 96-h log10CFU was largest for sequential therapy with vancomycin followed by ceftaroline (−5.22 ± 1.2,P= 0.010 versus ceftaroline) and for sequential therapy with vancomycin followed by ceftaroline (−3.60 ± 0.6,P= 0.037 versus daptomycin), compared with daptomycin (−2.24 ± 1.0), vancomycin (−1.40 ± 1.8), and sequential therapy with vancomycin followed by daptomycin (−1.32 ± 1.0,P> 0.5 for the last three regimens). Prior exposure of vancomycin at 1 g q12h reduced the initial microbiological response of daptomycin, particularly for hVISA and VISA isolates, but did not affect the response of ceftaroline. In the scenario of poor vancomycin response for high-inoculum MRSA infection, a ceftaroline-containing regimen may be preferred.

Nemonoxacin enhances antibacterial activity and anti-resistant mutation ability of vancomycin against methicillin-resistant Staphylococcus aureus in an in vitro dynamic pharmacokinetic/pharmacodynamic model

2021 ◽  
Author(s):  
Junchen Huang ◽  
Siwei Guo ◽  
Xin Li ◽  
Fang Yuan ◽  
You Li ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antibacterial Activity ◽  
Bactericidal Activity ◽  
Pharmacodynamic Model ◽  
Methicillin Resistant ◽  
Mutant Prevention Concentration ◽  
Mrsa Infection ◽  
Independent Risk Factors ◽  
Resistant Mutation

Reduced susceptibility and emergence of resistance to vancomycin in methicillin-resistant Staphylococcus aureus (MRSA) have led to the development of various vancomycin based combinations. Nemonoxacin is a novel nonfluorinated quinolone with antibacterial activity against MRSA. The present study aimed to investigate the effects of nemonoxacin on antibacterial activity and the anti-resistant mutation ability of vancomycin for MRSA and explore whether quinolone resistance genes are associated with a reduction in the vancomycin minimal inhibitory concentration (MIC) and mutant prevention concentration (MPC) when combined with nemonoxacin. Four isolates, all with a vancomycin MIC of 2 μg/mL, were used in a modified in vitro dynamic pharmacokinetic/pharmacodynamic model to investigate the effects of nemonoxacin on antibacterial activity (M04, M23 and M24) and anti-resistant mutation ability (M04, M23 and M25, all with MPC ≥19.2 μg/mL) of vancomycin. The mutation sites of gyrA , gyrB , parC , and parE of 55 clinical MRSA isolates were sequenced. We observed that in M04 and M23, the combination of vancomycin (1g q12h) and nemonoxacin (0.5g qd) showed a synergistic bactericidal activity and resistance enrichment suppression. All clinical isolates resistant to nemonoxacin harbored gyrA (S84→L) mutation; gyrA (S84→L) and parC (E84→K) mutations were the two independent risk factors for the unchanged vancomycin MPC in combination. Nemonoxacin enhances the bactericidal activity and suppresses resistance enrichment ability of vancomycin against MRSA with a MIC of 2 μg/mL. Our in vitro data support the combination of nemonoxacin and vancomycin for the treatment of MRSA infection with a high MIC.

scholarly journals Antimicrobial Activity of Lemongrass Essential Oil (Cymbopogon flexuosus) and Its Active Component Citral Against Dual-Species Biofilms of Staphylococcus aureus and Candida Species

2020 ◽  
Vol 10 ◽  
Author(s):  
Shanjun Gao ◽  
Guangzhi Liu ◽  
Jianguo Li ◽  
Jing Chen ◽  
Lina Li ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Essential Oil ◽  
Pathogenic Bacteria ◽  
Expression Of Genes ◽  
Cymbopogon Flexuosus ◽  
Underlying Mechanisms ◽  
Bacteria And Fungi ◽  
Conventional Antibiotics ◽  
Lemongrass Essential Oil

Compared to mono-species biofilm, biofilms formed by cross-kingdom pathogens are more refractory to conventional antibiotics, thus complicating clinical treatment and causing significant morbidity. Lemongrass essential oil and its bioactive component citral were previously demonstrated to possess strong antimicrobial efficacy against pathogenic bacteria and fungi. However, their effects on polymicrobial biofilms remain to be determined. In this study, the efficacy of lemongrass (Cymbopogon flexuosus) essential oil and its bioactive part citral against dual-species biofilms formed by Staphylococcus aureus and Candida species was evaluated in vitro. Biofilm staining and viability test showed both lemongrass essential oil and citral were able to reduce biofilm biomass and cell viability of each species in the biofilm. Microscopic examinations showed these agents interfered with adhesive characteristics of each species and disrupted biofilm matrix through counteracting nucleic acids, proteins and carbohydrates in the biofilm. Moreover, transcriptional analyses indicated citral downregulated hyphal adhesins and virulent factors of Candida albicans, while also reducing expression of genes involved in quorum sensing, peptidoglycan and fatty acids biosynthesis of S. aureus. Taken together, our results demonstrate the potential of lemongrass essential oil and citral as promising agents against polymicrobial biofilms as well as the underlying mechanisms of their activity in this setting.

scholarly journals β-lactam Antibiotics Stimulate the Pathogenicity of Methicillin-resistant Staphylococcus aureus Via SarA-controlled Tandem Lipoprotein Expression

2018 ◽  
Author(s):  
Weilong Shang ◽  
Yifan Rao ◽  
Ying Zheng ◽  
Yi Yang ◽  
Qiwen Hu ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Proinflammatory Cytokine ◽  
Abscess Formation ◽  
Global Regulator ◽  
Methicillin Resistant ◽  
Cytokine Levels ◽  
Mrsa Infection ◽  
Subinhibitory Concentrations

AbstractMethicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of nosocomial infections worldwide. MRSA resists nearly all β-lactam antibiotics that have a bactericidal activity and a signal inducer effect. However, studies have yet to clarify whether the inducer effect of empirically used β-lactams stimulates MRSA pathogenicity in vivo. Here, we showed that a new cluster of tandem lipoprotein genes (tlpps) was upregulated in MRSA in response to the subinhibitory concentrations of β-lactam induction. The increased Tlpps significantly altered immune responses by macrophages with high IL-6 and TNFα levels. The deletion of the tlpps mutant (N315Δtlpps) significantly decreased the proinflammatory cytokine levels in vitro and in vivo. The bacterial loads of N315Δtlpps in the mouse kidney were also reduced compared with those of the wild type N315. The β-lactam-treated MRSA exacerbated cutaneous infections with increased lesion size, extended illness, and flake-like abscess-formation compared with those of the nontreatment. The β-lactam antibiotics that promoted the MRSA pathogenicity were SarA dependent, and the increasing expression of tlpps after β-lactam treatment was directly controlled by the global regulator SarA. Overall, our findings suggested that β-lactams should be used carefully because it might lead to a worse outcome of MRSA infection than inaction in the treatment.Author summaryβ-lactams are widely used in practice to treat infectious diseases, however, β-lactams worsening the outcome of a certain disease is poorly understood. In this study, we have identified a new cluster of tandem lipoprotein genes (tlpps) that is upregulated in the major clinically prevalent MRSA clones in response to the subinhibitory concentrations of β-lactams induction. The major highlight in this work is that β-lactams induce SarA expression, and then SarA directly binds to the tlpp cluster promoter region and upregulates the tlpp expression in MRSA. Moreover, the β-lactam stimulated Tlpps are important virulence factors that enhance MRSA pathogenicity. The deletion of the tlpps mutant significantly decreases the proinflammatory cytokine levels in vitro and in vivo. The β-lactam induced Tlpps enhance the host inflammatory responses by triggering the expression of IL-6 and TNFα, thereby promoting bacterial colonization and abscess formation. These data elucidate that β-lactams can worsen the outcome of MRSA infection through the induction of tlpps that are controlled by the global regulator SarA.

scholarly journals Rifampicin fails to eradicate mature biofilm formed by methicillin-resistant Staphylococcus aureus

2012 ◽  
Vol 45 (4) ◽  
pp. 471-474 ◽  
Author(s):  
Keli Cristine Reiter ◽  
Gustavo Enck Sambrano ◽  
Bárbara Villa ◽  
Thiago Galvão da Silva Paim ◽  
Caio Fernando de Oliveira ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Molecular Size ◽  
Bacterial Count ◽  
Minimal Bactericidal Concentration ◽  
Methicillin Resistant ◽  
Infection Treatment ◽  
Mrsa Infection ◽  
Count Recovery

INTRODUCTION: Antimicrobial activity on biofilms depends on their molecular size, positive charges, permeability coefficient, and bactericidal activity. Vancomycin is the primary choice for methicillin-resistant Staphylococcus aureus (MRSA) infection treatment; rifampicin has interesting antibiofilm properties, but its effectivity remains poorly defined. METHODS: Rifampicin activity alone and in combination with vancomycin against biofilm-forming MRSA was investigated, using a twofold serial broth microtiter method, biofilm challenge, and bacterial count recovery. RESULTS: Minimal inhibitory concentration (MIC) and minimal bactericidal concentration for vancomycin and rifampicin ranged from 0.5 to 1mg/l and 0.008 to 4mg/l, and from 1 to 4mg/l and 0.06 to 32mg/l, respectively. Mature biofilms were submitted to rifampicin and vancomycin exposure, and minimum biofilm eradication concentration ranged from 64 to 32,000 folds and from 32 to 512 folds higher than those for planktonic cells, respectively. Vancomycin (15mg/l) in combination with rifampicin at 6 dilutions higher each isolate MIC did not reach in vitro biofilm eradication but showed biofilm inhibitory capacity (1.43 and 0.56log10 CFU/ml reduction for weak and strong biofilm producers, respectively; p<0.05). CONCLUSIONS: In our setting, rifampicin alone failed to effectively kill biofilm-forming MRSA, demonstrating stronger inability to eradicate mature biofilm compared with vancomycin.

scholarly journals Risk factors associated with MRSA

2018 ◽  
Vol 33 (3) ◽  
pp. 76-79
Author(s):  
Sonal Gupta ◽  
Bibhabati Mishra ◽  
Archana Thankur ◽  
Vinita Dogra ◽  
Poonam S. Loomba ◽  
...  
Keyword(s):  
Risk Factors ◽  
Staphylococcus Aureus ◽  
Antibiotic Therapy ◽  
Antimicrobial Agents ◽  
Treatment Options ◽  
Erythromycin Resistance ◽  
Methicillin Resistant ◽  
Hospitalised Patients ◽  
Mrsa Infection

Background: Methicillin-resistant Staphylococcus aureus (MRSA) infection is associated with increased morbidity and mortality compared with infections caused by methicillin-sensitive Staphylococcus aureus (MSSA). Treatment of MRSA infection is complicated by the fact that these organisms are resistant to multiple antimicrobial agents, so treatment options are limited. The aim of the present study is determine risk factors association with MRSA as compared with MSSA and to compare the minimum inhibitory concentrations (MICs) of vancomycin, teicoplanin, linezolid and erythromycin to MRSA and MSSA.Methods: A nine-month prospective study was carried out. Staphylococcus aureus strains with clinical correlation, isolated from hospitalised patients, were included in the study. MIC of vancomycin, teicoplanin, linezolid and erythromycin was determined by E-test (HIMEDIA). Risk factors such as immunosuppression, previous hospitalisation, surgical procedure done, invasive devices and antibiotic therapy were determined by a pre-set protocol.Results: A total of 62 S. aureus strains were included in the study. Some 40% of S. aureus strains were methicillin resistant. The risk factors, invasive devices, previous hospitalisation and comorbid illness were found to be significantly associated with MRSA. Borderline significant association was observed with immunosuppression and antibiotic therapy. Erythromycin resistance was observed in 56% of MRSA, while no resistance was observed in MSSA. Teicoplanin MIC50 values and mean MIC were found to be lowest in vitro among vancomycin and linezolid against both MRSA and MSSA. The efficacy of teicoplanin, in terms of clinical and microbiological cure, has not been proven to be superior to vancomycin, but it has a better toxicity profile and has demonstrated a reduced risk of adverse events. Conclusions: Minimising risk factors and attention to alternative antibiotics and infection control practices may ease the problem of management of infections with MRSA.

scholarly journals 1218. Retapamulin as a Potential Decolonizing Agent: Activity against Mupirocin-Resistant Strains From Pediatric Patients With Methicillin-Resistant Staphylococcus aureus Infection

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S369-S370
Author(s):  
Ami Patel ◽  
Jennifer Lighter-Fisher ◽  
Yi Fulmer ◽  
Richard Copin ◽  
Adam Ratner ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Pediatric Patients ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Promising Alternative ◽  
Methicillin Resistant ◽  
Mrsa Infection ◽  
Mupirocin Resistance ◽  
Research Grant

Abstract Background Controlling methicillin-resistant Staphylococcus aureus (MRSA) colonization is a common strategy to prevent transmission and recurrent infection. Standard decolonization regimens include nasal application of mupirocin ointment; however, increasing rates of mupirocin-resistance (Mup-R) have been noted globally. At our institution there has been an increase in community-acquired MRSA (CA-MRSA) infections among children living in Brooklyn, New York. A genotypic geographic cluster of an outbreak clone of the CA-MRSA strain USA 300 with a high rate (&gt;85%) of mupirocin resistance, mediated by the plasmid borne mupA gene, was identified prompting investigation into an alternative decolonizing agent. We sought to investigate retapamulin, a topical pleuromutilin antibiotic, which has been shown to be effective against S. aureus with in vitro and in vivo activity against MRSA and a low propensity to develop resistance. Methods Broth microdilution was used to determine the minimum inhibitory concentrations (MIC) of retapamulin against 53 Mup-R MRSA isolates collected from pediatric patients (aged 9 months–17 years) presenting to our institution over an 18 month period with clinical MRSA infection. Susceptibility defined as ≤0.5 mg/L susceptible (EUCAST). Whole genome sequence data were analyzed for the presence of rplC and cfr gene mutations known to confer resistance to retapamulin. Results All 53 isolates were susceptible to retapamulin. 49/53 (92%) strains were inhibited at MIC 0.25 mg/L, 2/53 (4%) at MIC 0.125 mg/L, and 2/53 (4%) at MIC 0.5 mg/L. DNA sequence analysis showed that one isolate had a first-step mutation in the rplC gene, but it was not associated with reduced phenotypic susceptibility to retapamulin, as the MIC of that isolate was 0.25 mg/L. Conclusion Retapamulin demonstrated excellent in vitro activity against a genotypic cluster of Mup-R isolates from pediatric patients presenting to our institution with MRSA infection. These data suggest that retapamulin may be a promising alternative decolonization therapy for MRSA and a viable option to prevent the spread of mupirocin-resistant MRSA clones. Further research includes an ongoing randomized, placebo-controlled trial testing the in vivo efficacy of retapamulin as a nasal and perirectal decolonizing agent in children. Disclosures A. Patel, Aqua Pharmaceuticals: Investigator inititiated grant, Research grant. J. Lighter-Fisher, Aqua Pharmaceuticals: Investigator Initiated Grant, Research grant.

scholarly journals Immunization with a Bacterial Lipoprotein Establishes an Immuno-Protective Response with Upregulation of Effector CD4+ T Cells and Neutrophils Against Methicillin-Resistant Staphylococcus aureus Infection

Pathogens ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 138 ◽  
Author(s):  
Zhenzi Peng ◽  
Duo-Yao Cao ◽  
Hui-Ya Wu ◽  
Suguru Saito
Keyword(s):  
Staphylococcus Aureus ◽  
T Cell ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Neutrophil Function ◽  
Effector Memory ◽  
Protective Response ◽  
Methicillin Resistant ◽  
Mrsa Infection ◽  
Prevention And Cure

Staphylococcus aureus (S. aureus) is a commensal bacterium in the human body; however, the bacterium frequently generates serious inflammation and infectious diseases. Some strains of S. aureus, such as methicillin-resistant Staphylococcus aureus (MRSA), are still a serious problem in public health facilities. Thus, an effective protection strategy is eagerly expected for the prevention and cure of MRSA infection. Here, we report that a specific fraction of an S. aureus lipoprotein (SA-LP) established a protective response against MRSA infection. The fractionated S. aureus lipoprotein SA-LP-F2, which is contained in 30–50 kDa of crude S. aureus lipoprotein (SA-LP-C), effectively activated dendritic cells (DCs) and the SA-LP-F2-pulsed DCs generated IFN-γ+CD4+ T (Th1) and IL-17A+CD4+ T (Th17) cells by in vitro antigen presentation. The SA-LP-F2 immunization upregulated the Th1 and Th17 populations so that MRSA colonization on the skin was suppressed during the challenge phase with MRSA. By following the effector T cell upregulation, the neutrophil function, which was a substantial effector cell against MRSA, was also enhanced in the SA-LP-F2-immunized mice. Finally, we found that the protective effect of SA-LP-F2 immunization was maintained for at least 90 days because the immunized mice continued to show a protective response during the MRSA challenge period. In the MRSA challenge, reactivated Th1 and Th17 populations were maintained in the SA-LP-F2-immunized mice as compared to naive mice. In addition, the neutrophil population was also upregulated in the mice. The memory CD4+ T cell (central memory T; TCM and effector memory T; TEM) population was established by SA-LP-F2 immunization and was maintained at higher levels than usual. Taken together, our findings may provide a breakthrough in the establishment of an immunization strategy against MRSA infection.

scholarly journals The Stringent Response Contributes to Persistent Methicillin-Resistant Staphylococcus aureus Endovascular Infection Through the Purine Biosynthetic Pathway

2020 ◽  
Vol 222 (7) ◽  
pp. 1188-1198 ◽  
Author(s):  
Liang Li ◽  
Arnold S Bayer ◽  
Ambrose Cheung ◽  
Lou Lu ◽  
Wessam Abdelhady ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Biosynthetic Pathway ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Stringent Response ◽  
Response Mechanism ◽  
Methicillin Resistant ◽  
Life Threatening ◽  
Mrsa Infection ◽  
Outcome Differences

Abstract Persistent methicillin-resistant Staphylococcus aureus (MRSA) endovascular infections represent a significant clinical-therapeutic challenge. Of particular concern is antibiotic treatment failure in infections caused by MRSA that are “susceptible” to antibiotic in vitro. In the current study, we investigate specific purine biosynthetic pathways and stringent response mechanism(s) related to this life-threatening syndrome using genetic matched persistent and resolving MRSA clinical bacteremia isolates (PB and RB, respectively), and isogenic MRSA strain sets. We demonstrate that PB isolates (vs RB isolates) have significantly higher (p)ppGpp production, phenol-soluble-modulin expression, polymorphonuclear leukocyte lysis and survival, fibronectin/endothelial cell (EC) adherence, and EC damage. Importantly, an isogenic strain set, including JE2 parental, relP-mutant and relP-complemented strains, translated the above findings into significant outcome differences in an experimental endocarditis model. These observations indicate a significant regulation of purine biosynthesis on stringent response, and suggest the existence of a previously unknown adaptive genetic mechanism in persistent MRSA infection.

scholarly journals In Vitro and In Vivo Activity of 14-O-[(4,6-Diamino-pyrimidine-2-yl) thioacetyl] Mutilin against Methicillin-Resistant Staphylococcus aureus

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3277
Author(s):  
Yunxing Fu ◽  
Chunqing Leng ◽  
Yuan Fan ◽  
Xia Ma ◽  
Xianghui Li ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antibacterial Agent ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Skin Wound ◽  
Methicillin Resistant ◽  
Wound Model ◽  
New Antibiotics ◽  
Mrsa Infection

Staphylococcus aureus (S. aureus) is a major human pathogen that requires new antibiotics with unique mechanism. A new pleuromutilin derivative, 14-O-[(4,6-Diamino-pyrimidine-2-yl) thioacetyl] mutilin (DPTM), has been synthesized and proved as a potent antibacterial agent using in vitro and in vivo assays. In the present study, DPTM was further in vitro evaluated against methicillin-resistant Staphylococcus aureus (MRSA) isolated from dairy farms and outperformed tiamulin fumarate, a pleuromutilin drug used for veterinary. Moreover, a murine skin wound model caused by MRSA infection was established, and the healing effect of DPTM was investigated. The results showed that DPTM could promote the healing of MRSA skin infection, reduce the bacterial burden of infected skin MRSA and decrease the secretion of IL-6 and TNF-α inflammatory cytokines in plasma. These results provided the basis for further in-depth drug targeted studies of DPTM as a novel antibacterial agent.

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