Bacterial toxins can wreak mass havoc within cells by shutting down multiple essential functions at once, a new study has found.
The study focused on how one bacterial toxin called ACD (a type linked to cholera and poisoning by raw oysters) modifies an abundant cellular protein called actin and converts it into a secondary toxin. Actin is involved in a host of processes including muscle contraction, cell division, cellular communication and immune response.
The researchers wanted to better understand how a relatively small amount of bacterial toxin could do such swift, significant damage to a strong network of actin. Their study appears in the journal Current Biology.
In theory, the actin's abundance within every single human cell should make it a difficult to disable - and disabling targets is the business of a bacterial toxin looking to gum up the immune system and make a human or animal sick.
When the team looked at what was happening in real time in a living cell, they were able to understand how quickly and efficiently the toxin took over - and how that happened.
The toxin cripples the action of "instructor" proteins, many of which share a common property - the ability to bind several actin molecules at once. By permanently linking together several actin molecules, ACD toxin converts them into a new universal toxin that binds tightly to those "instructors" and blocks their activity.
This amplifies toxicity and disorganizes the cell, and it doesn't take much. A tiny fraction of actin - about 2 percent within a given cell - is affected. The toxin is then redirected toward less-abundant targets, which leads to a cascade of cellular changes that break down normal function. Previous work led to a better understanding of this activity outside of a living cell.
"This is basically like crippling a nation by disabling all its instructors: political and military leadership, teachers and others. The population (actin) is there, but without proper instructions most transportation, imports and exports, border protection and other normal activities are halted or disorganized all at once," senior author said.
Toxins are the key to bacteria's power to make people and animals sick. A single molecule of some of the most lethal toxins - those released by bacteria that cause whooping cough and dysentery, for example - can kill an entire cell.
"When antibiotics worked effectively, we worried less about these processes in the cell, but today we must better understand how bacteria thrive in our bodies so that scientists might someday find alternative ways to fight them," author said.
https://news.osu.edu/news/2018/05/03/research-toxin-power/
https://www.cell.com/current-biology/fulltext/S0960-9822(18)30423-8
Latest News
Ancient viral DNA in the hu…
By newseditor
Posted 26 May
AI to analyze clumping prot…
By newseditor
Posted 26 May
Reversible, non-hormonal ma…
By newseditor
Posted 26 May
Dissection of the schizophr…
By newseditor
Posted 26 May
Protease action on controll…
By newseditor
Posted 25 May
Other Top Stories
Check-point inhibitors exacerbate NASH induced liver cancer
Read more
AI used to understand asbestos-linked cancer
Read more
Protein rewires cancer cell metabolism to promote metastasis
Read more
The role of hypoxia-inducible factors in tumor growth and suppression
Read more
Dual treatment to kill small cell lung cancer (SCLC) cells
Read more
Protocols
SEMORE: SEgmentation and MO…
By newseditor
Posted 26 May
Spatially resolved lipidomi…
By newseditor
Posted 24 May
Efficient expansion and CRI…
By newseditor
Posted 21 May
Massively parallel in vivo…
By newseditor
Posted 20 May
Breast cancer-on-chip for p…
By newseditor
Posted 16 May
Publications
Integrating human endogenou…
By newseditor
Posted 26 May
The thalamic reticular nucl…
By newseditor
Posted 26 May
PMI-controlled mannose meta…
By newseditor
Posted 26 May
Protein-membrane interactio…
By newseditor
Posted 26 May
Toward an interventional sc…
By newseditor
Posted 26 May
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar