TOP MEDICAL NEWS 06/AUGUST/2022

In a new study published in Nature Microbiology, Dr. Maria Carvalho, Dr. Kirsty Sands and a network of international colleagues decided to look at the presence of antibiotic resistance genes (ARGs) in the gut microbiota – the collection of microbes that are present in the human gut – of mothers and their babies from 7 LMICs in Africa and South Asia.

They recruited 35,040 mothers and 36,285 neonates from LMICS. From there, they collected 18,148 rectal swabs, which were used to grow the bacteria present in these samples and assess the presence of clinically important ARGs in the microbiota of mothers and their babies. The authors found that a large number of samples carried genes linked to antibiotic resistance, suggesting that AMR is far more widespread in these settings than previously anticipated.

Ref:

Dr. Maria Carvalho, Dr. Kirsty Sands et. al, Antibiotic resistance genes in the gut microbiota of mothers and linked neonates with or without sepsis from low and middle-income countries, Nature Microbiology, 4-Aug-2022

2. Better, ready-made CAR T cells for cancer immunotherapy

A technique developed by the lab of George Q. Daley, MD, Ph.D., in the Boston Children's Hospital Stem Cell Program, could make CAR T-cell therapy more widely accessible.

It can be difficult to gather enough functional T cells from a patient's blood, and manufacturing CAR T cells for each individual patient is expensive and takes time — time patients may not have on their side. Using induced pluripotent stem cells (iPS cells), Daley and his colleagues developed a method to make generic CAR T cells that could be produced at scale for use in multiple patients.

While iPS cells are, in theory, a limitless source of different cell types, Daley, first author Ran Jing, Ph.D., and their colleagues had to overcome the challenge of deriving mature, fully functioning T cells from which CAR T cells could be made. In the past, researchers have struggled with this because of the tendency for iPS cells to produce immature, embryonic cells in the Petri dish.

Ref:

Ran Jing, George Q. Daley et. al, EZH1 repression generates mature iPSC-derived CAR T cells with enhanced antitumor activity, Cell Stem Cell, 4-Aug-2022, DOI: 10.1016/j.stem.2022.06.014,

3. Molecular map that reveals insights into the genetic drivers of chronic lymphocytic leukemia

To provide a more thorough understanding of the biological underpinnings of CLL and its molecular subtypes, scientists set out to construct a map from the largest CLL dataset to date.

A newly constructed map of the landscape of genetic changes in chronic lymphocytic leukemia (CLL), a type of cancer of the blood and bone marrow that exists in diverse forms and arises from various causes, provides a better understanding of this complex malignancy that could lead to more accurate prognoses for patients, improved diagnostics, and novel treatments. The work is published in Nature Genetics

To build the CLL map, the team analyzed variations in genetic sequences, gene expression patterns, and chemical modifications to DNA—or genomic, transcriptomic, and epigenomic data—from 1,148 patients.

Ref:

Catherine Wu et. al, Molecular map of chronic lymphocytic leukemia and its impact on the outcome, Nature Genetics, 4-Aug-2022, DOI: 10.1038/s41588-022-01140-w

4. Engineered E Coli from stool which can survive a hostile gut environment long enough to treat the disease

Now, a group of researchers from the University of California, San Diego, successfully engineered E. coli collected from both human and mice gut microbiomes and showed that they have the potential to treat diseases such as diabetes. Their finds are published in the journal Cell.

The team first collected stool samples from the host and extracted E. coli for further modifications. "We say to the bacteria: Hey, we will give you a new superpower, which you may not even benefit from, but we will put you right back into the environment that you thrive in," says Zarrinpar.

The superpower that the team gave to these specific bacteria is a protein called bile salt hydrolase (BSH). After a single treatment in mice, E. coli with BSH were found throughout the entire gut of the mice and they retained their BSH activity for the entire lifetime of the host. The group also show that the BSH activity was able to positively influence diabetes progression in mice.

Ref:

Amir Zarrinpar et. al, Intestinal Transgene Delivery with Native E. coli Chassis Allows Persistent Physiological Changes, Cell, 4-Aug-2022, DOI: 10.1016/j.cell.2022.06.050