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Phage Therapy and Antibiotic Resistance

The remarkable achievements of modern medical science in the development of antibiotics and vaccines marked a temporary victory in the battle against bacterial pathogens. As the plasticity of bacteria and the ability to develop drug resistance to circumvent treatment is well understood, we must consider new approaches to managing bacterial diseases. Creative Biolabs is dedicated to providing strong support in solving problems in phage therapies and antibiotic resistance.

Antibiotic Resistance of Bacteria

Antimicrobial resistance in bacteria is one of the greatest biological and clinical medical challenges, as these pathogens rapidly mutate and deposit, thereby immunizing existing treatments. Bacterial resistance arises from the fact that antibacterial therapy is not fully studied and the heavy use of antibiotic combinations in medicine and agriculture. The use of bacterially insensitive antibiotics to treat bacterial diseases or prevent bacterial infections results in increased resistance to bacterial agents in nature. Even narrow-spectrum bacteria that were initially curable by a single low-dose antibiotic were forced to give high-dose combinations of antibiotics to overcome their accumulated resistance, which further led to the development of broad-spectrum-resistant bacteria.

Resistance to antibiotics among the strains of K. pneumoniae (A), P. aeruginosa (B), S. aureus (C), and E. faecium (D).Fig.1 Resistance to antibiotics among the strains of K. pneumoniae (A), P. aeruginosa (B), S. aureus (C), and E. faecium (D). (Kuptsov, 2020)

Antibiotic-resistant Bacteria and ESKAPE Pathogens

The widespread of bacteria and the accumulation of drug resistance pose a severe challenge to existing treatments, and WHO has proposed a global list of priority antibiotic-resistant bacteria to guide the development of new antimicrobial agents, including the notorious ESKAPE Pathogens (Enterococcus faecalis, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter sp.).

Priority Antibiotic-Resistant Bacteria Drug to Which It Is Resistant
CRITICAL Acinetobacter baumannii Carbapenem
Pseudomonas aeruginosa Carbapenem
Enterobacteriaceae Carbapenem, 3rd generation cephalosporins
HIGH Enterococcus faecium Vancomycin
Staphylococcus aureus Methicillin, Vancomycin intermediate, and resistant
Helicobacter pylori Clarithromycin
Campylobacter Fluoroquinolones
Salmonella spp. Fluoroquinolones
Neisseria gonorrhoeae 3rd generation cephalosporins and fluoroquinolone
MEDIUM Streptococcus pneumoniae Penicillin
Haemophilus influenzae Ampicillin
Shigella spp. Fluoroquinolone

Among ESKAPE pathogens, methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum beta-lactamase-producing Escherichia coli and vancomycin-resistant Enterococci (VRE) are the most common pathogens. Carbapenem-resistant Klebsiella pneumoniae, colistin-resistant, and imipenem-resistant Acinetobacter baumannii/Pseudomonas aeruginosa have also been observed in recent years. These drug-resistant bacteria develop resistance through four main mechanisms, including enzymatic inactivation/alteration of drugs, changes in drug binding sites, changes in cell permeability, and biofilm formation.

Phage Therapy for Drug-resistant Bacteria

Currently used antibiotics are very ineffective against infections caused by these resistant bacteria, especially those caused by ESKAPE pathogens. Therefore, methods such as synthetic chemicals, bacteriophages, antimicrobial peptides, nanomaterials, photodynamic therapy, and athermal plasma heat treatment have been proposed as alternatives. Among them, bacteriophage stands out as a therapeutic concept with few negative effects such as toxicity. Well-characterized, highly purified, and virulent selected phages can be used in situations where antibiotic drugs fail and serve as excellent and promising tools for microbial pathogen suppression. Various phages against ESKAPE pathogens and other pathogenic bacteria have been isolated, purified, and characterized, including phage PD-6A3 and Abp1 against imipenem against Acinetobacter baumannii, and Sb-1 phage family against Staphylococcus aureus. Several more well-performing phage cocktails are undergoing clinical trials and being sold as commercial products.

Phage vBAb-M-G7 infects and lyses Acinetobacter baumannii strain G7.Fig.2 Phage vBAb-M-G7 infects and lyses Acinetobacter baumannii strain G7. (Rohde, 2018)

The research status and application of phage therapy methods for different bacterial species, disease types, and application fields are listed on other pages:

The advancement of modern medicine has given us a temporary upper hand in the battle against bacteria, but we also have to face the crisis brought about by the spread of bacterial resistance. With our strong technology platform and cutting-edge theoretical knowledge, Creative Biolabs is ready to help you understand the phage therapies against antibiotic-resistant bacteria. We also want to provide reliable experimental models and standardized assays to customers around the world to help you better characterize your phages of interest. Please do not hesitate to contact us for more information.

References:

  1. Kuptsov, N.S.; et al. Efficacy of commercial bacteriophage products against ESKAPE pathogens. Microbiology. 2020, 3: 18-24.
  2. Rohde, C.; et al. Bacteriophages: a therapy concept against multi-drug–resistant bacteria. Surgical Infections. 2018, 19(8): 184.
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