BENGALURU: Like thieves that continuously search for methods to evade seize, Salmonella enterica, a disease-causing bacterium, makes use of numerous techniques to flee the human physique’s defence mechanisms, an Indian Institute of Science (IISc) examine has discovered.
The brand new examine, revealed in Microbes and An infection, researchers from IISc’s division of microbiology and cell biology (MCB), 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 known as lysosomes or autophagosomes, which destroy the micro organism,” IISc mentioned.
Nonetheless, these micro organism have developed sturdy 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 may digest them,” IISc added.
Within the examine the crew deduced {that a} vital 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 scholar 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, aiding in eradicating phosphate teams from phosphoinositide, a kind 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 crew had reported that the variety of lysosomes produced by host cells decreases upon an infection with Salmonella… Mutant micro organism that had been unable to supply SopB had been additionally unable to cut back host lysosome numbers. Due to this fact, they determined to look extra intently on the position that SopB was enjoying within the manufacturing of lysosomes, utilizing superior imaging methods,” IISc mentioned.
What they discovered was that SopB prevents translocation of a vital molecule known as Transcription Issue EB (TFEB) from the cytoplasm (materials inside a cell aside from nucleus) of the host cell into the nucleus. This translocation is important 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,” the crew mentioned, including that SopB modifications key dynamics of SCV affecting TFEB’s translocation into the nucleus.
“Whereas different teams have already reported the perform of SopB in mediating invasion in epithelial cells, the novelty of our examine lies in identification of the perform of SopB in inhibiting the vacuolar fusion with present autophagosomes/lysosomes, and the second mechanism, which gives Salmonella with a survival benefit by rising the ratio of SCV to lysosomes,” says Dipshikha Chakravortty, professor at MCB and corresponding creator of the examine.
The researchers recommend that utilizing small molecule inhibitors in opposition to SopB or activators of TFEB might help counter Salmonella an infection.
In subsequent research, the crew plans to discover the position of one other host protein known as Syntaxin-17 whose ranges additionally scale back throughout Salmonella an infection. “How do the SCVs scale back the degrees of Syntaxin-17? Do they trade it with another molecules, or do the micro organism degrade it? We [plan to] look into it subsequent,” says Chakravortty.
The brand new examine, revealed in Microbes and An infection, researchers from IISc’s division of microbiology and cell biology (MCB), 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 known as lysosomes or autophagosomes, which destroy the micro organism,” IISc mentioned.
Nonetheless, these micro organism have developed sturdy 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 may digest them,” IISc added.
Within the examine the crew deduced {that a} vital 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 scholar 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, aiding in eradicating phosphate teams from phosphoinositide, a kind 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 crew had reported that the variety of lysosomes produced by host cells decreases upon an infection with Salmonella… Mutant micro organism that had been unable to supply SopB had been additionally unable to cut back host lysosome numbers. Due to this fact, they determined to look extra intently on the position that SopB was enjoying within the manufacturing of lysosomes, utilizing superior imaging methods,” IISc mentioned.
What they discovered was that SopB prevents translocation of a vital molecule known as Transcription Issue EB (TFEB) from the cytoplasm (materials inside a cell aside from nucleus) of the host cell into the nucleus. This translocation is important 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,” the crew mentioned, including that SopB modifications key dynamics of SCV affecting TFEB’s translocation into the nucleus.
“Whereas different teams have already reported the perform of SopB in mediating invasion in epithelial cells, the novelty of our examine lies in identification of the perform of SopB in inhibiting the vacuolar fusion with present autophagosomes/lysosomes, and the second mechanism, which gives Salmonella with a survival benefit by rising the ratio of SCV to lysosomes,” says Dipshikha Chakravortty, professor at MCB and corresponding creator of the examine.
The researchers recommend that utilizing small molecule inhibitors in opposition to SopB or activators of TFEB might help counter Salmonella an infection.
In subsequent research, the crew plans to discover the position of one other host protein known as Syntaxin-17 whose ranges additionally scale back throughout Salmonella an infection. “How do the SCVs scale back the degrees of Syntaxin-17? Do they trade it with another molecules, or do the micro organism degrade it? We [plan to] look into it subsequent,” says Chakravortty.
