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Biosensor for Detection of Antibiotic Resistant Staphylococcus Bacteria

Biosensor for Detection of Antibiotic Resistant Staphylococcus Bacteria

Published on: May 8, 2013

Bacteriophage-derived endolysins restore antibiotic susceptibility in β-lactam- and macrolide-resistant Streptococcus

Niels Vander Elst¹, Kristine Farmen¹, Lisa Knörr¹

¹Department of Neuroscience, Karolinska Institute, Stockholm, Sweden.

Molecular Medicine (Cambridge, Mass.)

|May 5, 2025

Abstract:

Streptococcus pneumoniae, the pneumococcus, is a cause of major illness globally. Invasive pneumococcal disease (IPD) is characterized by pneumococci invading blood (bacteremia), lungs (pneumonia), or brain and cerebrospinal fluid (meningitis). Meningitis remains an important global health concern because half of the survivors experience long-term neurological damage. The antibiotics commonly used to treat pneumococcal infections are β-lactams and macrolides, however, S. pneumoniae is nowadays often resistant to one or several antibiotics, therefore novel antimicrobials are needed. Here, we found that the bacteriophage-derived cpl-1 endolysin showed consistent antibacterial activity against β-lactam- and macrolide-resistant pneumococcal clinical strains grown in human blood and human cerebrospinal fluid. Exploiting synergistic and additive mechanisms, supplementation of cpl-1 to either penicillin or erythromycin, as representatives for β-lactam and macrolide antibiotics, rescued human neuronal cells from the cytotoxicity of antibiotic-resistant pneumococcal infections. Finally, systemic administration of cpl-1 supplemented to penicillin in mice infected with penicillin-resistant pneumococci successfully reduced bacteremia, and, thanks to the efficient penetration across the blood-brain barrier, abolished bacterial load in the brain, resulting in increased (89%) survival accompanied by an asymptomatic course of infection. These findings strongly suggest that cpl-1 can enhance antibiotic susceptibility in β-lactam- and macrolide-resistant S. pneumoniae, serving as a valuable adjunct therapy to standard-of-care antibiotics for multidrug-resistant IPD.

Insights

A novel bacteriophage endolysin, cpl-1, effectively combats antibiotic-resistant Streptococcus pneumoniae. This adjunct therapy enhances standard antibiotics, improving survival rates for invasive pneumococcal disease.

Area of Science:

Microbiology
Infectious Diseases
Pharmacology

Background:

Streptococcus pneumoniae causes significant global illness, including invasive pneumococcal disease (IPD).
Antibiotic resistance in S. pneumoniae to common treatments like β-lactams and macrolides necessitates novel therapeutic strategies.
Pneumococcal meningitis survivors often face long-term neurological deficits, highlighting the need for effective treatments.

Purpose of the Study:

To evaluate the antibacterial activity of bacteriophage-derived cpl-1 endolysin against multidrug-resistant Streptococcus pneumoniae.
To assess the efficacy of cpl-1 as an adjunct therapy to existing antibiotics for treating antibiotic-resistant pneumococcal infections.
To determine the therapeutic potential of cpl-1 in preclinical models of invasive pneumococcal disease.

Main Methods:

Tested cpl-1 endolysin activity against clinical strains of β-lactam- and macrolide-resistant S. pneumoniae in human blood and cerebrospinal fluid.
Investigated the synergistic effects of combining cpl-1 with penicillin or erythromycin on neuronal cell protection against resistant pneumococci.
Administered cpl-1 combined with penicillin systemically in a mouse model of penicillin-resistant pneumococcal infection.

Main Results:

Cpl-1 demonstrated consistent antibacterial activity against resistant pneumococcal strains in human biological fluids.
Supplementation with cpl-1 rescued human neuronal cells from cytotoxicity induced by antibiotic-resistant pneumococci.
In mice, cpl-1 plus penicillin reduced bacteremia, penetrated the blood-brain barrier, cleared bacteria from the brain, and increased survival to 89%.

Conclusions:

Bacteriophage endolysin cpl-1 shows significant potential as an adjunct therapy for multidrug-resistant invasive pneumococcal disease.
Cpl-1 can restore susceptibility to conventional antibiotics like penicillin and erythromycin in resistant S. pneumoniae strains.
Cpl-1 represents a promising novel antimicrobial candidate for combating challenging pneumococcal infections, particularly meningitis.

Read full analysis

Keywords:

Streptococcus pneumoniae Antibiotic-resistance Endolysins Erythromycin Inflammation Invasive Pneumococcal Disease Meningitis Neuronal damage New Antimicrobial Strategy Penicillin Synergy

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