Highlights SIP is a new protein phosphatase 2A-containing protein complex SIP is essential for the asymmetric localization of SIN components to the SPB SIP is required for the SPB localization of the SIN inhibitor Byr4p SIP promotes dephosphorylation of the SIN scaffold protein Cdc11p
A naturally occurring predatory bacterium is able to work with the immune system to clear multi-drug resistant Shigella infections in zebrafish. It is the first time the predatory bacterium Bdellovibrio bacteriovorus has been successfully used as an injected anti-bacterial therapy and represents an important step in the fight against drug-resistant infections, or ‘superbugs’.
Shigella infection is responsible for over 160 million illnesses and over 1 million deaths every year – and is a common cause of ‘travellers’ diarrhea.’ Cases of drug-resistant Shigella are also on the rise as, although the diarrhea usually clears up without treatment, antibiotics are often used even in mild cases to stop the diarrhea faster.
To investigate Bdellovibrio’s ability to control drug resistant Gram-negative infections, researchers injected zebrafish larvae with a lethal dose of Shigella flexneri strain M90T, resistant to both streptomycin and carbenicillin antibiotics. Bdellovibrio was then injected into the larvae’s infection site, and a decrease in the number of Shigella was seen. In the absence of Bdellovibrio, zebrafish were unable to control the replication of Shigella and levels of the bacteria rose.
Wellcome Research Career Development Fellow Dr Serge Mostowy from Imperial College London said: “This study really shows what a unique and interesting bacterium Bdellovibrio is as it presents this amazing natural synergy with the immune system and persists just long enough to kill prey bacteria before being naturally cleared.”
Bdellovibrio can invade and kill a range of Gram-negative bacteria, eg E. coli and Salmonella, in the natural environment. Previous research has shown that it can reduce pathogen numbers in the stomach of chickens when taken as an oral therapy, but there is growing need to develop therapies to target infections in wounds and organs. It may tackle a range of drug-resistant Gram-negative bacterial infections in hospital patients.
Remarkably, Bdellovibrio is also able to reduce pathogen load in immunocompromised zebrafish larvae depleted of white blood cells. However, survival is significantly greater in immune-competent zebrafish, showing that Bdellovibrio’s maximum therapeutic benefit comes from its ability to work cooperatively with the host’s own immune system.
Dr Michael Chew at Wellcome said: “It may be unusual to use a bacterium to get rid of another, but in the light of the looming threat from drug resistant infections the potential of beneficial bacteria-animal interactions should not be overlooked. We are increasingly relying on last line antibiotics, and this innovative study demonstrates how predatory bacteria could be an important additional tool to drugs in the fight against resistance.” https://wellcome.ac.uk/press-release/harnessing-power-predatory-bacteria-%E2%80%98living-antibiotic
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