Antibiotic Alternatives and Combinational Therapies for Bacterial Infections

The thoughtless person playing with penicillin treatment is morally responsible for the death of the man who succumbs to infection with the penicillin-resistant organism.” As Alexander Fleming predicted already in 1945 bacteria have become resistant to antibiotics. From time to time we are bombarded with news of infections and deaths caused by antibiotic resistant and multiple drug resistant superbugs. This increase of resistance towards commonly used antibiotics due to decades of use, misuse and abuse of antibiotics, is today a global health concern. Research investments on development of new antimicrobials that can fight antimicrobial resistant microorganisms are scarce yet some new antibiotic discoveries have been described recently. Nevertheless, the advent of antibiotic failure due to bacterial resistance has brought interest in other alternative therapies. Natural products from microbial origin are examples of such alternative therapies. Bacteriophages are bacterial viruses and consequently bacterial natural enemies and together with their derived enzymes are efficient towards antibiotic resistant bacteria. Antimicrobial peptides (AMP), natural compounds with alternative mechanisms of action, are short-length peptides present in a variety of sources and in many forms. AMP have been recognized as promising candidates for replacing classical antimicrobials due to their multiple mechanisms of action and general low specificity in terms of molecular targets, which reduces the chance of acquired resistance. Quorum sensing inhibitors (QSI) are destabilisers of key communication mechanisms that regulate virulence and the establishment of biofilm-related infections.

This type of approach is believed to not only diminish the development of antimicrobial resistance, but also to improve the treatment of recalcitrant multi-drug resistant infections. Another promising antimicrobial strategy may rely on the use of enzymes that can prevent/disturb infections in different ways, as they can directly: attack microorganism causing cell lysis; impair the intercellular communication when quorum sensing molecules are the target; catalyse reactions which result in the production of antimicrobial compounds, among others. Additionally to the vast interest in searching and testing alternative bio-inspired therapies, research on combinatorial therapies which may include combination of two or more natural antimicrobial agents or even combinations with conventional drugs are achieving growing interest since they hold great potential regarding: the increase of the antimicrobial spectrum; the prevention of resistance; the reduction of toxicity and side effects; and the reach of synergistic activity.