Potentiële therapeutische toepassing van bacteriofagen en faag-afgeleide endolysinen als alternatieve behandeling van boviene mastitis

Abstract

The increase in bacterial drug resistance causes major difficulties in the clinical treatment of a growing number of bacterial infections worldwide. Consequently, there is an urgent need to develop novel anti-bacterial agents to control these resistant pathogens and to complement the currently used antibiotics. Mastitis is the most prevalent disease impacting dairy cattle, and therefore one of the costliest diseases in the global dairy industry. The excessive use of curative as well as preventive antibiotics in this sector entails a real risk for the emergence of antimicrobial resistance. Moreover, these traditional antimicrobial agents are often ineffective and lead to residues in the milk, which can affect dairy product consumers. As an alternative therapeutic approach, bacteriophages and phage-encoded endolysins have been proposed and are currently (re)investigated as potential antibacterial agents against mastitis.

Characterization of the Bacteriophage-Derived Endolysins PlySs2 and PlySs9 with In Vitro Lytic Activity against Bovine Mastitis Streptococcus uberis

“…Several preventive, prophylactic and therapeutic measures have been proposed to combat this infectious disease, but antibiotics currently remain the standard antimicrobial preventive and therapeutic treatment [6,9]. This systematic (over)use of antibiotics in the dairy sector is being questioned and as such, endolysins have been proposed as either replacement or add-on strategy [14,16,18]. We here characterized two endolysins, i.e., PlySs2 and PlySs9, with muralytic activity against bovine mastitis-causing S. uberis.…”

“…The use of bacteriophages (phages) and their lytic enzymes have been proposed as strategies that may supplement the current antibiotic arsenal [14][15][16][17][18]. Although phage therapy was initially considered promising, more recent insights revealed several remaining hurdles i.e., unpredictable pharmacokinetics and -dynamics, large molecular size compared to antibiotics, low tissue penetration, narrow bacterial specificity, the necessity to replicate in vivo, elevation of the somatic cell count in the cow's milk and inactivation of bacteriophage by whey proteins [19][20][21].…”

“…Local, topical therapy as well as single intravenous injections are either recently available on the pharmaceutical market or in full development, albeit only for human applications [25,26]. Hence, endolysins offer an interesting potential within the context of veterinary medicine [14,[16][17][18]. More specifically, several endolysins have already been proposed to target Gram-positive pathogens associated with bovine mastitis [27][28][29][30][31].…”

Treating Bacterial Infections with Bacteriophage-Based Enzybiotics: In Vitro, In Vivo and Clinical Application

“…Nevertheless, due to their proteinaceous nature, they may induce allergic reactions. PGHs can be applied not only in medicine [ 273 ] but also in the food industry [ 172 , 174 , 202 , 213 , 242 , 274 , 275 , 276 , 277 , 278 , 279 , 280 ], during biofuel production [ 210 , 281 ], in agriculture [ 282 , 283 , 284 ], and in veterinary medicine [ 258 , 285 , 286 , 287 , 288 , 289 , 290 , 291 , 292 , 293 ]. As with PSDs, they are suitable for a range of formulations and can be delivered via different routes, such as topical (creams, ointments, and gels), injections (intravenous or intraperitoneal), orally, transnasally, or vaginally [ 55 , 157 , 158 ].…”

Bacteriophage-derived endolysins as innovative antimicrobials against bovine mastitis-causing streptococci and staphylococci: a state-of-the-art review

“…Bacteriophages, or shortly phages, are viruses that infect bacteria [ 1 – 3 ]. Phages recognize specific receptors on the cell wall of bacterial species or strains, which cause them to adsorb and inject their DNA.…”