To gain insight into this quick response, we tested whether it re

To gain insight into this quick response, we tested whether it requires de novo protein synthesis. Cells were treated with an excess concentration of rifampicin and chloramphenicol to inhibit transcription and translation, respectively and then exposed to a low pH. Analysis by TLC showed that the increase in CL in Ncls2 was unaffected by treatment with these inhibitors (Fig. 3). In the present study,

we first showed that Cls1 compensates for the stalled function of Cls2 under conditions of acute low-pH stress. This response did not require de novo Cls1 synthesis, suggesting that Cls1 is equipped RG7204 mw with a backup system that can respond swiftly to such an emergency. In the human body, low-pH conditions play a protective role against pathogens. In a fasting stomach, the pH is 1–1.5, which is a strong barrier against incoming bacteria. The acidic environment of the vagina (˜pH 4) is maintained by commensal Lactobacillus spp. (Dover et al., 2008).

Also, the surface of the skin is enriched with various organic acids, including propionic acids, lactic see more acid and pyruvic acid produced by host cells and the cells of the microbiota (Holland, 1993). Quick drying of the skin concentrates these organic acids, leading to a sudden acid shock. In macrophages, engulfed bacteria are challenged by a series of bactericidal factors, including acidification in the phagosome lumen (pH 5). Staphylococcus aureus, as a commensal bacterium and opportunistic pathogen, is Phospholipase D1 occasionally challenged by an acidic environment; however, it is capable of increasing its acid tolerance through its Cls1 backup system. Membrane composition can significantly affect

cell survival in response to acid exposure. In Streptococcus mutans, an increase in monounsaturated fatty acids is important for acid adaptation (Fozo & Quivey, 2004). Furthermore, the same group recently reported that CL is a reservoir for monounsaturated fatty acids, and they showed that a cls mutant of S. mutans was acid-sensitive (Macgilvray et al., 2012). Consistent with this, CL in S. aureus is also important for acid resistance (compare with wild-type cells vs. the Ncls1/cls2 double mutant in Fig. 2). An important difference is that in S. mutans CL synthesis depends on a single Cls, while S. aureus has a Cls1 backup system in addition to the housekeeping gene cls2. The present study raises a number of questions regarding the Cls1 backup system, including how Cls2 is inactivated by a low pH and how Cls1 function is initiated. Future studies should focus on the subcellular localization of these proteins, the optimal pH for enzymatic activity and activity control through specific modifications. It is also important to address why other types of stress induce Cls1-dependent CL synthesis. In the present study, we tested the effect of ‘single’ stressors on Cls1 function; however, in a natural environment, multiple stressors assault S. aureus simultaneously (e.g.

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