Methicillin-Resistant Staphylococcus aureus

Brumfitt, W.; Hamilton‐Miller, J. M. T.

doi:10.1056/nejm198905043201806

Cited by 534 publications

(176 citation statements)

References 105 publications

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“…Due to the prevalence of multidrug-resistant bacteria, especially the emergence of superbugs (46,47), there is an urgent need for novel therapeutic agents that are directed against such pathogens. Phage lysin (48) and the natural products derived from traditional Chinese medicine (49) are considered novel therapeutic agents because their mechanism of action is different from that of antibiotics.…”

Section: Figmentioning

confidence: 99%

Combination Therapy of LysGH15 and Apigenin as a New Strategy for Treating Pneumonia Caused by Staphylococcus aureus

Xia

Wang

et al. 2016

Appl Environ Microbiol

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c Pneumonia is one of the most prevalent Staphylococcus aureus-mediated diseases, and the treatment of this infection is becoming challenging due to the emergence of multidrug-resistant S. aureus, especially methicillin-resistant S. aureus (MRSA) strains. It has been reported that LysGH15, the lysin derived from phage GH15, displays high efficiency and a broad lytic spectrum against MRSA and that apigenin can markedly diminish the alpha-hemolysin of S. aureus. In this study, the combination therapy of LysGH15 and apigenin was evaluated in vitro and in a mouse S. aureus pneumonia model. No mutual adverse influence was detected between LysGH15 and apigenin in vitro. In animal experiments, the combination therapy showed a more effective treatment effect than LysGH15 or apigenin monotherapy (P < 0.05). The bacterial load in the lungs of mice administered the combination therapy was 1.5 log units within 24 h after challenge, whereas the loads in unprotected mice or mice treated with apigenin or LysGH15 alone were 10.2, 4.7, and 2.6 log units, respectively. The combination therapy group showed the best health status, the lowest ratio of wet tissue to dry tissue of the lungs, the smallest amount of total protein and cells in the lung, the fewest pathological manifestations, and the lowest cytokine level compared with the other groups (P < 0.05). With regard to its better protective efficacy, the combination therapy of LysGH15 and apigenin exhibits therapeutic potential for treating pneumonia caused by MRSA. This paper reports the combination therapy of lysin and natural products derived from traditional Chinese medicine. Staphylococcus aureus is a ubiquitous and zoonotic pathogen that causes high morbidity and mortality in a variety of diseases, ranging from skin and soft tissue infections to necrotizing pneumonia and overwhelming sepsis (1, 2). S. aureus pneumonia is one of the most prevalent S. aureus-mediated diseases and accounts for 13.3% of all invasive S. aureus infections (3). Treatment of S. aureus infection has become increasingly difficult, given the prevalence of multidrug-resistant S. aureus strains, especially the widespread existence of methicillin-resistant S. aureus (MRSA) strains (4). MRSA strains are typically resistant to multiple antibiotics, including gentamicin, erythromycin, fluoroquinolones, and ofloxacin, among others (5). There are also reports of vancomycin-resistant S. aureus (VRSA), raising serious concerns within the medical community (6-8). Therefore, there is an urgent need for novel therapeutic strategies that are efficient against this pathogen.Lysin, which is encoded by the phage (bacterial virus) genome at the end of the phage lytic life cycle to lyse the host cell, can rapidly and specifically lyse Gram-positive bacteria when exogenously applied (9). Because the bacterial cell wall is conserved and necessary for the life cycle, the current lack of bacterial resistance against lysin is not surprising (10). In addition, its species specificity or type specificity ensures that lysin w...

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Section: Figmentioning

confidence: 99%

Combination Therapy of LysGH15 and Apigenin as a New Strategy for Treating Pneumonia Caused by Staphylococcus aureus

Xia

Wang

et al. 2016

Appl Environ Microbiol

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“…is a main cause of nosocomial infections (4). This type of MRSA is alternatively called hospital-acquired MRSA (HA-MRSA).…”

Section: Methicillin-resistant Staphylococcus Aureus (Mrsa)mentioning

confidence: 99%

Spread of Community‐Acquired Methicillin‐Resistant Staphylococcus aureus (MRSA) in Hospitals in Taipei, Taiwan in 2005, and Comparison of Its Drug Resistance with Previous Hospital‐Acquired MRSA

Takano

Saito

Teng

et al. 2007

Microbiology and Immunology

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“…taphylococcus aureus is a common pathogen with ability to develop resistance to virtually all classes of antibiotics (1)(2)(3). Infections caused by S. aureus, especially, methicillin-resistant S. aureus (MRSA) (4,5), are becoming a serious problem worldwide; therefore, there is an urgent need to develop effective therapeutic agents against MRSA (6).…”

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confidence: 99%

Novel Chimeric Lysin with High-Level Antimicrobial Activity against Methicillin-Resistant Staphylococcus aureus In Vitro and In Vivo

Yang

Zhang

et al. 2014

Antimicrob Agents Chemother

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The treatment of infections caused by methicillin-resistant Staphylococcus aureus (MRSA) is a challenge worldwide. In our search for novel antimicrobial agents against MRSA, we constructed a chimeric lysin (named as ClyH) by fusing the catalytic domain of Ply187 (Pc) with the non-SH3b-like cell wall binding domain of phiNM3 lysin. Herein, the antimicrobial activity of ClyH against MRSA strains in vitro and in vivo was studied. Our results showed that ClyH could kill all of the tested clinical isolates of MRSA with higher efficacy than lysostaphin as well as its parental enzyme. The MICs of ClyH against clinical S. aureus strains were found to be as low as 0.05 to 1.61 mg/liter. In a mouse model, a single intraperitoneal administration of ClyH protected mice from death caused by MRSA, without obvious harmful effects. The present data suggest that ClyH has the potential to be an alternative therapeutic agent for the treatment of infections caused by MRSA.

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Methicillin-Resistant Staphylococcus aureus

Cited by 534 publications

References 105 publications

Combination Therapy of LysGH15 and Apigenin as a New Strategy for Treating Pneumonia Caused by Staphylococcus aureus

Combination Therapy of LysGH15 and Apigenin as a New Strategy for Treating Pneumonia Caused by Staphylococcus aureus

Spread of Community‐Acquired Methicillin‐Resistant Staphylococcus aureus (MRSA) in Hospitals in Taipei, Taiwan in 2005, and Comparison of Its Drug Resistance with Previous Hospital‐Acquired MRSA

Novel Chimeric Lysin with High-Level Antimicrobial Activity against Methicillin-Resistant Staphylococcus aureus In Vitro and In Vivo

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