Fueled by their surprise finding when analyzing environmental bacteria, Johns Hopkins Medicine researchers have now taken the primary steps to help develop better and more effective antibiotics in the future.

In their study published in the mBio journal, the team detailed how removing the OpgH protein from the Caulobacter crescentus, a widely known bacterium, leads to cell death. 

Erin Goley, Ph.D., biochemistry professor at JHUSOM and the study's senior author, said:

    "In our experiments, when we get rid of the protein OpgH in Caulobacter bacteria, which halts production of OPG sugar molecules, the bacteria can't survive."

OpgH is responsible for synthesizing osmoregulated periplasmic glucans (OPGs) or glucose-containing molecules that occupy the gelatinous spaces within the bacteria's protective cell envelope. Removing OpgH leads to the absence of sugar molecules, causing the cell envelope to lose its shape and weaken. 

The team used an inducible promoter to study the importance of OpgH in the bacterium. Through this molecular tool, they discovered that the enzyme's absence disrupts the signaling pathway called CenKR and removes the bacterium's ability to detect and repair issues in the envelope. 

In addition, researchers found that hyperactivating the CenKR pathway by tricking the cell to produce excessive amounts of the CenR protein also causes trouble.

Goley explained:

    "We found that they became misshapen as we dialed down the OpgH protein and halted the production of sugar OPG molecules, or hyperactivated the CenKR signaling pathway that maintains the cell envelope." 

She added that after manipulating OpgH or CenR in the bacterium, they noticed that the molecular players had shifted their positions, proving that both proteins are crucial in maintaining the cell's shape and, eventually, the cell's survival.

In the next phase of their research, the team plans to investigate how different enzymes function within bacterial cells to aid the development of drugs that can specifically target these enzymes.

Read the full article here to learn more about OpgH's role in bacterial cell survival.

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