A new lead for disarming antibiotic-resistant bacteria
Bacteria-infecting viruses may have novel uses in medicine

Date:
November 3, 2020
Source:
Texas A&M AgriLife Communications
Summary:
A virus can stop bacteria from sharing genes for antibiotic
resistance among themselves, researchers have discovered. The
results hint at new ways to treat infections and describe a
new feature of a highly diverse, largely unexplored part of the
biosphere.



FULL STORY ==========================================================================
A virus can stop bacteria from sharing genes for antibiotic resistance
among themselves, Texas A&M AgriLife researchers have discovered. The
results hint at new ways to treat infections and describe a new feature
of a highly diverse, largely unexplored part of the biosphere.


==========================================================================
The study, published recently in Proceedings of the National Academy
of Sciences, was led by Lanying Zeng, Ph.D., associate professor in
the Texas A&M College of Agriculture and Life Sciences Department of Biochemistry and Biophysics.

How some phages infect bacteria Viruses that only infect bacteria are
called bacteriophages, or phages for short. Phages are the most numerous biological entities on Earth. Soil is rife with phages, as is the human
gut, and phages that infect and destroy bacteria have found promising
uses in combating antibiotic-resistant bacterial infections.

Some phages only infect bacteria whose surface contains cylindrical
structures called pili. Named after the Latin word pilus, for spear,
pili allow bacteria to transfer genes for advantageous traits, such as
drug resistance, and enhance bacteria's ability to move and to attack
host cells. Because of pili's link to bacterial virulence, researchers
have wondered whether new medications could be created to inactivate
this feature. While the ways bacteria benefit from pili are clear,
how phages use pili to infect bacteria has remained elusive.

Phage competition Zeng's team used fluorescence microscopy to delve into
how a phage, MS2, enters an E. coli cell. The researchers created MS2
phages that fluoresce and are fully infectious and stable. The phages
attach to pili on E. coli cells, making the pili visible through a
fluorescence microscope.



========================================================================== Through a series of experiments, Zeng, her graduate student Laith Harb,
and the other coauthors obtained a detailed description of what happens
when an MS2 phage infects an E. coli.

The team discovered that after a phage attaches to a pilus, the pilus
retracts, bringing the phage to the bacterial cell surface. The pilus
then breaks off behind the phage. Whereas healthy E. coli replenish
broken pili, cells infected by MS2 do not. In this way, other phages
are prevented from infecting the same cell. The first phage to reach
the cell gains a competitive advantage.

"It's like, 'OK, this cell is mine.' Phages set up their own territory,"
said Zeng, who is a core faculty member of the Center for Phage
Technology, a part of Texas A&M AgriLife Research.

Because the phenomenon gives such a boost to the infecting phage, this occurrence may be widespread among other phage strains that employ pili
to infect bacteria, Zeng added.

New ideas for medicine The results may be of use in medicine, Zeng
said. First, using phages to decrease bacterial virulence may give the
immune system time to fight off an infection. Second, the results point
to a way of dealing with infections that may be gentler for patients
than antibiotics or than using phage therapy to destroy bacteria.

"One advantage of our method versus traditional phage therapy is that
you do not kill the cell, you just disarm it," Zeng said. "Killing
the cell may cause a problem, because inside the cell you may have
a toxin that could be released into the host." Phages that target
pili could also reinforce the action of antibiotics. Some bacterial
infections only respond to high doses of antibiotics, which can cause
side effects. Adding phages to the mix may allow doctors to decrease
the needed antibiotic dosage.


========================================================================== Story Source: Materials provided by
Texas_A&M_AgriLife_Communications. Note: Content may be edited for style
and length.


========================================================================== Journal Reference:
1. Laith Harb, Karthik Chamakura, Pratick Khara, Peter J. Christie, Ry
Young, Lanying Zeng. ssRNA phage penetration triggers detachment
of the F-pilus. Proceedings of the National Academy of Sciences,
2020; 117 (41): 25751 DOI: 10.1073/pnas.2011901117 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/11/201103104746.htm

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