Examine highlights two methods utilized by Salmonella to flee the human physique’s defenses

Like thieves that consistently search for methods to evade seize, Salmonella enterica, a disease-causing bacterium, makes use of varied ways to flee the human physique’s protection mechanisms. In a brand new examine, researchers from the Division of Microbiology and Cell Biology (MCB), IISc, spotlight two such methods that the bacterium makes use of to guard itself, each pushed by the identical protein.

When Salmonella enters the human physique, every bacterial cell resides inside a bubble-like construction referred to as Salmonella-containing vacuole (SCV). In response to the bacterial an infection, the immune cells in our physique produce reactive oxygen species (ROS) and reactive nitrogen species (RNS), together with pathways triggered to interrupt down these SCVs and fuse them with mobile our bodies referred to as lysosomes or autophagosomes, which destroy the micro organism. Nevertheless, these micro organism have developed strong mechanisms to keep up vacuolar integrity, which is essential for his or her survival. For instance, when a bacterial cell divides, the vacuole surrounding it additionally divides, enabling each new bacterial cell to be ensconced in a vacuole. This additionally ensures that extra vacuoles are current than the variety of lysosomes which might digest them.

Within the examine printed in Microbes and An infection, the IISc workforce deduced {that a} crucial protein produced by Salmonella, referred to as SopB, prevents each the fusion of SCV with lysosomes in addition to the manufacturing of lysosomes, in a two-pronged strategy to guard the bacterium. “[This] provides the higher hand to micro organism to outlive inside macrophages or different host cells,” explains Ritika Chatterjee, former PhD pupil in MCB and first creator of the examine. The experiments had been carried out on immune cell strains and immune cells extracted from mice fashions.

SopB acts as a phosphatase – it aids in eradicating phosphate teams from phosphoinositide, a sort of membrane lipid. SopB helps Salmonella change the dynamics of the vacuole – particularly it alters the kind of inositol phosphates within the vacuole membrane – which prevents the vacuole’s fusion with lysosomes.

A earlier examine from the identical workforce had reported that the variety of lysosomes produced by the host cells decreases upon an infection with Salmonella. The researchers additionally discovered that mutant micro organism that had been unable to supply SopB had been additionally unable to scale back host lysosome numbers. Subsequently, they determined to look extra intently on the function that SopB was taking part in within the manufacturing of lysosomes, utilizing superior imaging strategies.

What they discovered was that SopB prevents the translocation of a crucial molecule referred to as Transcription Issue EB (TFEB) from the cytoplasm of the host cell into the nucleus. This translocation is significant as a result of TFEB acts as a grasp regulator of lysosome manufacturing.

That is the primary time we deciphered that SopB can work in a twin method – it adjustments the phosphoinositide dynamics of SCV and impacts TFEB’s translocation into the nucleus. Whereas different teams have already reported the operate of SopB in mediating invasion in epithelial cells, the novelty of our examine lies in identification of the operate of SopB in inhibiting the vacuolar fusion with current autophagosomes/lysosomes, and the second mechanism, which gives Salmonella with a survival benefit by rising the ratio of SCV to lysosomes.”

Dipshikha Chakravortty, Professor at MCB and corresponding creator of the examine

The researchers counsel that utilizing small molecule inhibitors towards SopB or activators of TFEB might help counter Salmonella an infection.

In subsequent research, the workforce plans to discover the function of one other host protein referred to as Syntaxin-17 whose ranges additionally cut back throughout Salmonella an infection. “How do the SCVs cut back the degrees of Syntaxin-17? Do they change it with another molecules, or do the micro organism degrade it? We [plan to] look into it subsequent,” says Chakravortty.