Thicker Bacterial Envelopes Impair Antibiotic Penetration During Active Mastitis Treatment

Staphylococcus aureus is among the bacteria commonly involved in infections in humans and animals, especially mastitis. An international research team led by INRAE and including ENS Paris-Saclay found that it is far more robust and virulent in milk than in serum or laboratory culture media.

Their results, published in Communications Biology, indicate that S. aureus uses milk lipids to build an envelope that is about three times thicker, which makes it much more resistant to antibiotic treatment.

The bacteria also make more of the pigment linked to their golden color, which increases their virulence during infection. The exceptional robustness of S. aureus in milk suggests that antibiotic treatment protocols for mastitis may need to be adjusted when milk is abundant, in both humans and animals.

Staphylococcus aureus is often present in infections in both humans and veterinary medicine. It gets its name from the golden-yellow pigment it produces, which helps increase virulence and defend against oxidative stress. Because it can survive antibiotic treatment, it remains a serious clinical problem.

To understand what drives this resistance, the scientists studied how the bacterium grows in two infection-relevant environments: milk and serum. Milk, produced by the mammary glands, offers a stable and nutrient-rich setting where S. aureus can grow and cause mastitis (infections of the mammary glands). Serum is the environment in which S. aureus develops during infection.

Milk: An Ideal Environment for Staphylococcus aureus

Staphylococcus aureus shows very different characteristics depending on whether it grows in milk or serum. In particular, the scientists observed changes in the lipid composition of its membrane. When grown in milk, S. aureus takes up milk lipids into its membrane rather than making its own. This leads to an envelope that is about three times thicker than that of bacteria grown in serum or laboratory culture media.

Milk lipids also encourage pigment production, which makes S. aureus more virulent and more resistant to oxidative stress. The scientists also tested the different antibiotics used to treat mastitis. When grown in milk, S. aureus becomes much more robust and resistant to the various antibiotics tested. This may be because the antibiotics target the envelope of S. aureus, which is thicker after growth in milk, or because they cause oxidative stress, which the bacterium resists better, thanks to its increased pigment production.

These results point to a specific link between milk lipids and the severity of Staphylococcus aureus infections. The bacterium’s strong robustness in milk may mean antibiotic treatment protocols for mastitis should be adjusted when milk is abundant, especially in humans and domestic animals. Research is also underway to develop combination therapies that pair an antibiotic with a molecule that stops the bacterium from taking in lipids from its environment.