Bacteriophages: immunological role and antimicrobial potential

Bakteriofagi su bakterijski virusi te najbrojniji i najraznovrsniji biološki organizmi na zemlji. Kod čovjeka, obilno su prisutni u crijevima, gdje igraju ključnu ulogu u sastavu mikrobioma, a osim u mukoznom sloju, gdje često obitavaju, pronađeni su u krvotoku i unutarnjim organima. U crijevima, ciljano uništavanje bakterija bakteriofagima često ima kaskadne učinke na bakterijske populacije koje nisu izravno ciljane predacijom faga. Rezidentne mikrobne zajednice crijeva imaju snažan utjecaj na imunološki sustav domaćina, a promjene tih zajednica potencijalno mogu dovesti do promjene ekosustava mikrobioma i razvoja bolesti. S druge strane, uslijed rastuće bakterijske rezistencije na antibiotike, bakteriofagi se desetljećima intenzivno proučavaju kao alternativa klasičnoj antibiotskoj terapiji. Preklinička i klinička ispitivanja pokazuju da bakteriofagi ciljano djeluju na bakterije, te se lakše primjenjuju u odnosu na klasične antibiotike jer nije potrebna uzastopna primjena kroz period od nekoliko dana ili tjedana. Isto tako, mogu uništavati strukture biofilma, te povećati osjetljivost rezistentnih bakterija na neke klase antibiotika. Međutim, kliničku uporabu sprječavaju određeni nedostaci ovih lijekova, poput transmisije genetičkog materijala čime se potencijalno mogu širiti geni rezistencije ili se njihova aktivnost može smanjiti uslijed imunološkog odgovora domaćina.Bacteriophages are obligate parasites that require a bacterial host to reproduce and are the most numerous and diverse biological organisms on planet Earth. In humans, they are abundantly present in the gut, where they play a key role in shaping the composition of the microbiome, and in addition to the mucous layer, where they often reside, they have been found in the bloodstream and internal organs. In the gut, targeted destroying bacteria by bacteriophages often has cascading effects on bacterial populations that were not directly targeted by phage predation. Resident microbial communities of the gut have a strong influence on the host immune system, and changes in these communities can potentially lead to changes in the microbiome ecosystem and disease development. On the other hand, due to the growing bacterial resistance to antibiotics, bacteriophages have been intensively studied for decades as an alternative to classical antibiotic therapy. Preclinical trials show that bacteriophages have targeting effect on bacteria and are easier to apply compared to classical antibiotics as there is no need for consecutive application over a period of several days or weeks. Bacteriophages can also destroy biofilm structures and increase the sensitivity of resistant bacteria to some classes of antibiotics. However, clinical use is hindered by certain disadvantages of these drugs, such as the transmission of genetic material which can potentially spread resistance genes or their activity can be reduced due to the host immune response