Mastitis harms cows, dairy farms, and treatment choices—but a virus-made enzyme may offer a way to break the bacteria’s defenses without relying only on antibiotics. Bovine mastitis caused by certain bacteria is common and has major economic effects on the dairy industry.

Hygiene, teat sealants, vaccination, and probiotics can control the disease, but they do not eliminate it completely. Effective treatment is still needed. Antibiotics can relieve the disease, but their use is increasingly questioned, especially when the drugs are important for human health.

Enzymes made by bacteria-infecting viruses may replace or complement those treatments. These enzymes are naturally designed to break open an infected bacterial cell from the inside, releasing new viruses. But using them from the outside is a different job.

Their effectiveness is not guaranteed, especially in the demanding conditions of an infected mammary gland. That limitation created an early obstacle to using natural versions as veterinary treatments. The enzymes break down the wall around certain bacteria.

Their structure has one part that does the cutting and another part that helps them attach to the bacterial wall. Those parts can be rearranged to make engineered versions with different ranges of bacteria they can destroy. The review compares natural and engineered versions linked to the bacteria that cause bovine mastitis.

It also groups highly similar enzymes so that differently named versions can be compared directly. The picture matters because these wall-cutting proteins can release new viruses from inside an infected bacterium—or be purified and applied from outside to break open a targeted Gram-positive bacterium, pointing to a possible way to fight bacterial infections.

The review groups natural enzymes with at least ninety-five percent protein-sequence similarity, then uses those groups to make comparisons easier. Engineered enzymes are discussed in the order in which they were published, with a general overview provided in a table.

One enzyme lost all of its cutting activity when the part that attaches to the bacterial wall was removed. That shows both parts are needed for full function. The attachment part could bind some streptococcal and staphylococcal bacteria, but not others.

The cutting part was therefore also important for complete binding. The enzyme was characterized as having potent biofilm-eradicating activity, showing that it could act against bacterial communities growing on surfaces. In human blood, its potency was substantially higher than in laboratory testing media, increasing by thirty-two to at least one hundred fold.

The researchers attributed this synergy to two key blood components, serum lysozyme and albumin, which worked together with the enzyme. One engineered enzyme was assembled from separate cutting and attachment parts, then selected for activity in treated whole milk. Its activity matched that of a comparison treatment, and both removed the target bacteria from that milk until none could be detected.

Combining the engineered enzyme with the comparison treatment produced a stronger effect, including against one bacterial type that resisted each treatment alone. But the crucial test exposed a problem: in raw cow’s milk, the engineered enzyme completely lost its activity.

Diluting the milk restored it, showing that milk components were blocking the enzyme. A later design was selected using raw cow’s milk instead. It still did not outperform the natural comparison treatment, did not show the expected cooperation with other enzymes, and faced a possible resistance problem.

Adding a short delivery piece increased its ability to kill bacteria inside mammary cells, but the added piece also reduced its antibacterial activity outside those cells. The review concludes that newer protein-design methods make it possible to create many enzyme variants and select promising ones under the conditions where they will actually be used.

Finding candidates that can withstand the demands of a lactating bovine mammary gland is now considered highly feasible. The review expects enzyme treatment, either alone or added to antibiotics, to approach a major change in veterinary medicine. It expects these virus-derived enzymes to become part of the antibiotic arsenal over the next decade, changing how infections behind bovine mastitis are treated.

The practical promise is to select endolysin candidates capable of withstanding the demands of the lactating bovine mammary gland. The review finds that these enzymes can work against mastitis bacteria, but raw milk and the udder can disable them. Designing and testing them under those real conditions may turn them into practical treatments.