Phage Therapy in Human Infectious Diseases

To overcome the barriers of growing and widespread drug resistance in pathogenic bacteria, researchers have investigated the use of phage therapy as an alternative or supplement to antibiotics to prevent bacterial infections in humans. Creative Biolabs is devoted to providing complementary expertise about phage therapy in human infectious diseases.

Phage Therapy in Human Infectious Diseases

Advances in modern medicine with antibiotics and vaccines have given us the upper hand in the battle against bacteria, but as populations rise and become more mobile, drug-resistant pathogens also spread widely.

Bacteriophages are viruses with bacteria as their specific hosts. Toxic phages directly decompose bacterial peptidoglycan through self-encoded endolysins, thereby killing targeted bacterial strains and controlling their population. In the field of human health, phage therapy is mainly used as a substitute or supplement for antibiotics or other drugs when antibiotics are difficult to take effect. Therefore, the research and application of phage therapy revolve around drug-resistant pathogenic microorganisms that can cause severe human disease, including the notorious ESKAPE pathogen.

Staphylococcus aureus

Staphylococcus aureus is a widespread gram-positive bacterium that causes foodborne illness and wound infections. With the emergence of methicillin-resistant Staphylococcus aureus and vancomycin-resistant Staphylococcus aureus, antibiotics have shown a decline in the control of Staphylococcus. At present, almost all known phages infecting Staphylococcus aureus belong to Podoviridae, Rhinoviridae, and Myoviridae.

Fig. 1 The morphology of Staphylococcus phage JD007. (Cui, 2017)

Enterococcus faecalis

Enterococcus faecalis is a Gram-positive streptococcus that mainly inhabits the human intestine. Ampicillin- and vancomycin-resistant Enterococcus can cause urinary tract infections or sepsis. Various phages have shown good targeting and killing ability of Enterococcus faecalis in experimental models or clinical tests.

Fig. 2 Inhibitory effect of Enterococcus faecalis phage vB_EfaS_HEf13 on the growth of Enterococcus faecalis. (Lee, 2019)

Klebsiella pneumoniae

Klebsiella pneumoniae is a gram-negative bacterium of the Enterobacteriaceae family and one of the most common pathogens of hospital-acquired disease. In recent years, Klebsiella pneumoniae, which has good resistance to lactams and carbapenems, has caused a major impact on modern medicine. Phages targeting Klebsiella pneumoniae have been extensively studied, and several of them have entered clinical trials, including SopranoGao, MezzoGao, AltoGao, Sweeny, vB_KpnS_Carvaje, Marfa, KPP5665-2, PMBT1, KpCHEMY26, KpGranit, vB_KpnS-MK54, vB_kpnM_17-11, etc.

Fig. 3 Multiplex genome alignment of three Klebsiella pneumoniae phages. (Bai, 2022)

Acinetobacter baumannii

Acinetobacter baumannii is a multi-site, gram-negative coccus bacterium that can survive on human hands for a long time and cause severe cross-infection. Carbapenem-resistant Acinetobacter baumannii has been identified in hospital settings. The killing ability of phages against Acinetobacter baumannii has been well characterized and verified by various experiments.

Fig. 4 Genome map of Acinetobacter baumannii phage vB_ApiM_fHyAci03. (Pulkkinen, 2019)

Pseudomonas aeruginosa

Pseudomonas aeruginosa is a gram-negative pathogen that can be found in human skin, respiratory tract, and intestinal tract. Pseudomonas aeruginosa tends to cause serious respiratory infections. Dozens of phages host Pseudomonas aeruginosa have been isolated and purified, and their killing ability and colony control ability have been proved in various experimental models, several of which have been clinically validated and officially used for Pseudomonas aeruginosa phage therapy.

Fig. 5 Characteristics of Pseudomonas aeruginosa phage C11. (Cui, 2016)

Enterobacter

Enterobacteriaceae are a class of gram-negative pathogens that cause enteritis and digestive tract infections and are one of the important pathogens of foodborne and hospital-acquired diseases. Enterobacterial phages that are currently under study or have entered clinical stage.

Fig. 6 Lysis ability of various types of E. coli phages against E. coli strains from different serotypes. (Korf, 2019)

Other Bacteria

ESKAPE pathogens are the best known and most widely studied drug-resistant microorganisms, but many other pathogens besides ESKAPE threaten human health and safety. Phages against some other bacterial pathogens that can cause severe infections have also been extracted, isolated, and characterized in recent years, and some of these potential phages have also demonstrated excellent bacterial killing ability and pathogen strain control ability.

Some other pathogenic microorganisms and corresponding phage therapy methods have been listed on other pages:

• Phage Therapy in Food Safety
• Phage Therapy in Agriculture
• Phage Therapy in Animal Health

Research and Application Status

At present, many mature phage therapy regimens have been clinically applied. To prevent bacteria from evolving the ability to evade recognition by phages, the vast majority of well-established phage therapy regimens are delivered through phage cocktails.

To better cope with the prevalent accumulation of drug resistance in pathogenic microorganisms and control the evolution of bacterial virulence/antibiotic resistance, phage therapy has become our most potent tool for pathogen antagonism. As a leading company in biological science and phage therapy development, Creative Biolabs provides strong support for the development of phage therapy in human infectious diseases. Please do not hesitate to contact us for more information.

References:

1. Cui, Zelin, et al. "Characterization and complete genome of the virulent Myoviridae phage JD007 active against a variety of Staphylococcus aureus isolates from different hospitals in Shanghai, China." Virology journal 14 (2017): 1-8. Under Open Access license CC BY 4.0, without modification.
2. Lee, Dongwook, et al. "The novel Enterococcus phage vB_EfaS_HEf13 has broad lytic activity against clinical isolates of Enterococcus faecalis." Frontiers in microbiology 10 (2019): 2877. Under Open Access license CC BY 4.0. The image was modified by extracting and using only Part A,B,C,D of the original image.
3. Bai, Jiawei, et al. "Isolation and characterization of vB_kpnM_17-11, a novel phage efficient against carbapenem-resistant Klebsiella pneumoniae." Frontiers in cellular and infection microbiology 12 (2022): 897531. Under Open Access license CC BY 4.0, without modification.
4. Pulkkinen, Elsi, et al. "Characterization of vB_ApiM_fHyAci03, a novel lytic bacteriophage that infects clinical Acinetobacter strains." Archives of virology 164.8 (2019): 2197-2199. Under Open Access license CC BY 4.0, without modification.
5. Cui, Xiaoli, et al. "Characterization of Pseudomonas aeruginosa phage C11 and identification of host genes required for virion maturation." Scientific reports 6.1 (2016): 39130. Under Open Access license CC BY 4.0, without modification.
6. Korf, Imke HE, et al. "Still something to discover: novel insights into Escherichia coli phage diversity and taxonomy." Viruses 11.5 (2019): 454. Under Open Access license CC BY 4.0, without modification.