Antimicrobial Alternatives against Antimicrobial-Resistant Pathogens

Dear Colleagues,

Bacteria are continually evolving into antibiotic resistant strains due to their extraordinary ability to adapt to changes in their environment such as encountering antibiotics. Global efforts to create potent antibiotics are constantly thwarted by bacteria which display fascinating combat strategies to survive despite the most innovative antibiotic mechanisms. Examples include, synthesis of the enzyme penicillinase by Staphylococcus aureus to destroy the antibiotic within 6 years of its introduction. Derivative methicillin’s victory did not last long and MRSA strains developed rapidly. Although vancomycin, a glycopeptide antibiotic, successfully stopped the spread of MRSA, vancomycin-intermediate-resistant S. aureus (VISA) currently exists and the emergence of vancomycin-resistant S. aureus (VRSA) is a realistic threat for the future. There are many other examples of drug- and multidrug-resistant (MDR) bacteria and, sadly, the list is continuously growing.

The development of new antimicrobial agents, however, is not currently capable of keeping up with the growing demand for antimicrobials that are active against MDR infections. New developments could be envisaged that contribute toward acceptance and widespread use of alternative therapies that would be able to stop returning back to pre-antibiotic era where essentially any infection could be fatal.

1.1. Vaccines and Antibodies

Vaccination has been traditionally used against viral diseases. Vaccination against bacterial diseases such as tuberculosis, diphtheria, tetanus, pertussis, Haemophilus influenzae type B, cholera, typhoid, and Streptococcus pneumoniae is less common. However, the rise of AMR among pathogenic bacteria revived this field.

Antibodies are very specific in targeting certain pathogens and thus they do not disrupt commensal microbiota. Development of resistance against them is highly unlikely. However, these alternative therapeutic agents are expensive and require substantial expenditures towards infrastructure and labour cost.

1.2. Bacteriophage Therapy

This is one of the oldest forms of therapy of infectious diseases, described before the Fleming’s (1929) discovery of naturally occurring antibiotic, penicillin. The success of antibiotics in controlling bacterial infectious diseases, however, overshadowed the development of this approach and it has been largely abandoned, persisting as limited R&D and therapy options in Russia, Georgia, and Poland. The rise of AMR among bacterial pathogens, however, revived the interest in phage therapy as an alternative, which is highly specific and less damaging to commensal microbiota compared to antimicrobials.

1.3. Antimicrobial Peptides

These have long been considered as potential replacements for antimicrobials but with limited success. Synthetic peptides and synthetic membrane-active agents may bring fresh prospective to this area.

1.4. Oligonucleotide Silencing

This approach, which is in the research stage, uses oligonucleotides for silencing AMR genes. This allows re-sensitizing drug-resistant bacteria and thus reinstate some antimicrobials that lost their efficiency.

1.5. Bacteriotherapy

Various probiotics have been used for hundreds of years. Faecal transplant therapy is a relatively recent approach, which, however, has already demonstrated some success in the treatment of chronic infections such as recurrent Clostridioides difficile infections and could be potentially be useful in a number of other diseases affecting the gut and beyond.

1.6. Photodynamic Therapy

Antibacterial photodynamic therapy is increasingly recognized as having a potential to effectively kill MDR pathogenic bacteria and for low probability of resistance development, which often happens with traditional antimicrobials.

1.7. Nanoparticles

The mechanisms of antibacterial action of nanoparticles are not fully understood. It is thought that the activity is complex and may include the induction of oxidative stress, release of metal ions that are toxic to bacteria, and also non-oxidative mechanisms.

1.8. Non-killing Antimicrobials

These antimicrobials can be defined as capable of preventing the realization of the full pathogenic potential of infectious agents. They do not necessarily kill a pathogen but reduce its virulence, thus reducing damage caused to a host and allowing the immune system to clear the pathogen. These antimicrobials may target quorum sensing and other systems involved in virulence, biofilm formation, immune evasion and other pathogenic properties.

1.9. Active Components of Traditional Medicines

Although usually perceived as contrasting to scientific medicine, traditional medicine may contain substances active against infectious agents. One of the best-known examples of this kind is the identification of a potent anti-malarial drug, artemisinin, in Artemisia plants, which were used for thousands of years as a remedy for many illnesses. Antimicrobial activity may present in a number of other traditional medicines as well, and identification and characterization of these compounds may enrich our arsenal of antimicrobial alternatives.

Prof. Rustam Aminov
Guest Editors

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• Bacteriophage Therapy
• Probiotics
• Lantibiotics
• Maggot Therapy
• Bacteriotherapy
• Bacteriophage lysins
• Antibiotic resistance
• “Super Bugs”