Exebacase: A Novel Approach to the Treatment of Staphylococcal Infections

McCarthy, Matthew W

doi:10.1007/s40268-022-00383-6

Cited by 6 publications

(5 citation statements)

References 50 publications

(61 reference statements)

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“…It was considered a lead therapeutic candidate in the endolysin field, evaluated in clinical trials by ContraFect. This company aimed a therapeutic application in humans suffering from sepsis and right-heart endocarditis caused by methicillin-resistant S. aureus (MRSA), as well as chronic prosthetic joint infections of the knee [ 73 ]. However, the company recently filed for bankruptcy.…”

Section: Reviewmentioning

confidence: 99%

“…PlySs2 was discovered in a prophage element of a S. suis isolate belonging to serotype 2 [ 16 , 75 ]. Multiple studies report that relatively low concentrations of PlySs2 can efficiently lyse S. aureus , S. agalactiae, S. dysgalactiae and S. uberis below detection limits in different kinds of qualitative and quantitative assays, including TRAs, TKAs, MIC/MBCs and in vivo studies [ 16 , 70 – 73 ]. This endolysin consists of an N-terminal CHAP and a C-terminal SH3_5.…”

Section: Reviewmentioning

confidence: 99%

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Bacteriophage-derived endolysins as innovative antimicrobials against bovine mastitis-causing streptococci and staphylococci: a state-of-the-art review

Vander Elst

2024

Acta Vet Scand

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Bacteriophage-encoded endolysins, peptidoglycan hydrolases breaking down the Gram-positive bacterial cell wall, represent a groundbreaking class of novel antimicrobials to revolutionize the veterinary medicine field. Wild-type endolysins exhibit a modular structure, consisting of enzymatically active and cell wall-binding domains, that enable genetic engineering strategies for the creation of chimeric fusion proteins or so-called ‘engineered endolysins’. This biotechnological approach has yielded variants with modified lytic spectrums, introducing new possibilities in antimicrobial development. However, the discovery of highly similar endolysins by different groups has occasionally resulted in the assignment of different names that complicate a straightforward comparison. The aim of this review was to perform a homology-based comparison of the wild-type and engineered endolysins that have been characterized in the context of bovine mastitis-causing streptococci and staphylococci, grouping homologous endolysins with ≥ 95.0% protein sequence similarity. Literature is explored by homologous groups for the wild-type endolysins, followed by a chronological examination of engineered endolysins according to their year of publication. This review concludes that the wild-type endolysins encountered persistent challenges in raw milk and in vivo settings, causing a notable shift in the field towards the engineering of endolysins. Lead candidates that display robust lytic activity are nowadays selected from screening assays that are performed under these challenging conditions, often utilizing advanced high-throughput protein engineering methods. Overall, these recent advancements suggest that endolysins will integrate into the antibiotic arsenal over the next decade, thereby innovating antimicrobial treatment against bovine mastitis-causing streptococci and staphylococci.

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Section: Reviewmentioning

confidence: 99%

Section: Reviewmentioning

confidence: 99%

Bacteriophage-derived endolysins as innovative antimicrobials against bovine mastitis-causing streptococci and staphylococci: a state-of-the-art review

Vander Elst

2024

Acta Vet Scand

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“…Thirty‐day mortality rates were 9.7% for CF‐301 in combination with antibiotics and 12.8% in the antibiotic only group. Subgroup analysis showed CF‐301 in combination with antibiotics reduced the 30‐day mortality of MRSA‐infected patients by 21% (McCarthy, 2022 ). Recently CF‐301 was examined in a randomized, double‐blind, placebo‐controlled phase III study examining efficacy and safety in patients receiving standard antibacterial therapy for the treatment of bacteraemia and endocarditis (NCT04160468).…”

Section: Bacteriophage and Phage Lysinsmentioning

confidence: 99%

Novel antimicrobial strategies to treat multi‐drug resistant Staphylococcus aureus infections

Douglas

Wulandari

Lovell

et al. 2023

Microbial Biotechnology

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Antimicrobial resistance is a major obstacle for the treatment of infectious diseases and currently represents one of the most significant threats to global health. Staphylococcus aureus remains a formidable human pathogen with high mortality rates associated with severe systemic infections. S. aureus has become notorious as a multidrug resistant bacterium, which when combined with its extensive arsenal of virulence factors that exacerbate disease, culminates in an incredibly challenging pathogen to treat clinically. Compounding this major health issue is the lack of antibiotic discovery and development, with only two new classes of antibiotics approved for clinical use in the last 20 years. Combined efforts from the scientific community have reacted to the threat of dwindling treatment options to combat S. aureus disease in several innovative and exciting developments. This review describes current and future antimicrobial strategies aimed at treating staphylococcal colonization and/or disease, examining therapies that show significant promise at the preclinical development stage to approaches that are currently being investigated in clinical trials.

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“…Exebacase (Lysin CF-301), an antistaphylococcal lysin, possesses ideal efficiency to clear staphylococcal biofilm. It has been investigated that exebacase removed all biofilms formed on catheters within 60 min and killed all released bacteria by 6 h ( 115 , 116 ). Exebacase not only destroys staphylococcal biofilm in chronic osteomyelitis but also has a rapid bactericidal effect.…”

Section: Immunotherapy Targetsmentioning

confidence: 99%

The effect of Staphylococcus aureus on innate and adaptive immunity and potential immunotherapy for S. aureus-induced osteomyelitis

Chen,

Liu,

Lin

et al. 2023

Front. Immunol.

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Osteomyelitis is a chronic inflammatory bone disease caused by infection of open fractures or post-operative implants. Particularly in patients with open fractures, the risk of osteomyelitis is greatly increased as the soft tissue damage and bacterial infection are often more severe. Staphylococcus aureus, one of the most common pathogens of osteomyelitis, disrupts the immune response through multiple mechanisms, such as biofilm formation, virulence factor secretion, and metabolic pattern alteration, which attenuates the effectiveness of antibiotics and surgical debridement toward osteomyelitis. In osteomyelitis, immune cells such as neutrophils, macrophages and T cells are activated in response to pathogenic bacteria invasion with excessive inflammatory factor secretion, immune checkpoint overexpression, and downregulation of immune pathway transcription factors, which enhances osteoclastogenesis and results in bone destruction. Therefore, the study of the mechanisms of abnormal immunity will be a new breakthrough in the treatment of osteomyelitis.

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Exebacase: A Novel Approach to the Treatment of Staphylococcal Infections

Cited by 6 publications

References 50 publications

Bacteriophage-derived endolysins as innovative antimicrobials against bovine mastitis-causing streptococci and staphylococci: a state-of-the-art review

Bacteriophage-derived endolysins as innovative antimicrobials against bovine mastitis-causing streptococci and staphylococci: a state-of-the-art review

Novel antimicrobial strategies to treat multi‐drug resistant Staphylococcus aureus infections

The effect of Staphylococcus aureus on innate and adaptive immunity and potential immunotherapy for S. aureus-induced osteomyelitis

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