mBio: How a typical gut bacterium travels from the gut

According to a new study from Weill Cornell Medical School, a typical gut bacterium that can spread throughout the body and cause serious infections, it fights natural immune defenses and antibiotics
by enhancing a protective outer layer called the cell envelope.
This finding offers a possible new way
to target these bacterial infections.

The study, published Nov.
10 in the journal mBio, sheds light on some of the potential changes
that can occur when E.
faecalis populations pass through intestinal epithelial cells and escape to other parts of the body.

"Systemic infection of fecal E.
coli can be fatal because of the microbe's extraordinary ability to adapt to a variety of environments and resist treatment," said lead researcher Diana K.
Morales, Ph.
D.
, assistant professor
of microbiology and immunology in obstetrics and gynecology at Weill Cornell Medical School.
People at risk of infection include those who are taking antibiotics or have compromised immune systems that promote the overgrowth
of Enterobacter faecalis in the gut.
Understanding how Enterobacter faecalis moves out of the gut and spreads may one day help scientists find the small molecules that stop the bacteria from spreading outside the gut, preventing dangerous infections
.

How this bacterium moves from the gut to other organs remains largely unexplored
.
However, Dr.
Morales said, the researchers observed that there were two different populations
of the same bacteria.
One population developed properties that allowed it to pass through the intestinal barrier, thereby acquiring favorable resistance to antimicrobials, while the other population remained unchanged
.

In a series of previous laboratory studies of this bacterium, the researchers found that the molecules produced by the moving Enterobacter faecalis are made up of sugar chains called polysaccharides that cause bacteria to aggregate or clump together
.
"When these bacteria clumped together, they seemed to develop an ability to move," Dr.
Morales said
.

In the current study, researchers including lead author Yusibeska Ramos, Ph.
D.
, found that the motility form of Enterococcus faecalis has a cell envelope containing large amounts of glycolipids, which are fat molecules
linked to carbohydrates.
The increase in cell membrane glycolipids appears to help bacteria fight extracellular stressors
.
These stressors include the antimicrobial agent daptomycin (a common drug used to treat Enterobacter faecalis infections) and -defensin (small molecules produced by intestinal epithelial cells to stop infection).

The researchers also found that genetic mutations that inhibit glycolipid production make Enterococcus faecalis more sensitive to these stressors and reduce the bacteria's ability to
penetrate the cell surface and pass through intestinal epithelial cells.

The researchers' next step is to evaluate more in vivo models to confirm whether the molecular pathways identified in the current study are necessary
for bacteria to leave the gut.
"We are also interested in identifying pharmacological approaches that can target these specific pathways, with the goal of one day helping patients better fight infections in this gut microbe," Dr
.
Morales said.

Journal Reference:

1. Yusibeska Ramos, Stephanie Sansone, Sung-Min Hwang, Tito A.
   Sandoval, Mengmeng Zhu, Guoan Zhang, Juan R.
   Cubillos-Ruiz, Diana K.
   Morales.
   Remodeling of the Enterococcal Cell Envelope during Surface Penetration Promotes Intrinsic Resistance to Stress.
   mBio, 2022; DOI: 10.
   1128/mbio.
   02294-22