Gatekeepers: Study discovers how microbes make it past tight spaces between cells

Jun 16, 2011
Staph (red) bacteria invading epithelial cells of mouse respiratory system (blue and green). Credit: Aoife Roche, PhD, Perelman School of Medicine, University of Pennsylvania

There are ten microbial cells for every one human cell in the body, and microbiology dogma holds that there is a tight barrier protecting the inside of the body from outside invaders, in this case bacteria. Bacterial pathogens can break this barrier to cause infection and senior author Jeffrey Weiser, MD, professor of Microbiology and Pediatrics from the Perelman School of Medicine at the University of Pennsylvania, and first author Thomas Clarke, PhD, a postdoctoral fellow in the Weiser lab, wondered how microbes get inside the host and circulate in the first place. Weiser and Clarke tested to see if microbes somehow weaken host cell defenses to enter tissues.

In this Cell Host & Microbe study, the investigators found that open and get through the initial cellular barrier -- epithelial cells that line the airway -- in a programmed and efficient way. They surmise this could be a normal physiological event and the epithelial lining may not be as effective at keeping microbes out as once thought. Microbes that survive once past the epithelial lining tend to be pathogenic, such as Streptococcus pneumoniae and Haemophilus influenzae, two major human pathogens causing invasive infections. Their data support a general mechanism for epithelial opening exploited by invasive pathogens to facilitate movement into tissue to initiate disease.

Using microarray and PCR analysis of the epithelial cells' response to invasion by S. pneumoniae and H. influenzae, the researchers found a downregulation of genes called claudins that encode proteins key to keeping the spaces between epithelial cells tight. All animals recognize molecules in microbial cell walls. It was detection of these microbial molecules by host molecules called Toll-like receptors that caused the proteins responsible for keeping the cellular barrier tight to fall down on the job.

When modeled in a cell assay, claudin downregulation was preceded by upregulation of another protein called SNAIL1 that suppresses claudins, the cellular components that keep the junctions tight. What's more, inhibiting claudin expression in a cell assay or stimulating the Toll-like receptors in an animal model loosened the junctions between cells and promoted bacterial movement across the epithelium.

"This study provides an understanding of how microbes gain access into their host to affect its physiology," concludes Weiser.

Explore further: Team publishes evidence for natural alternative to antibiotic use in livestock

add to favorites email to friend print save as pdf

Related Stories

Recommended for you

Researchers capture picture of microRNA in action

Oct 30, 2014

Biologists at The Scripps Research Institute (TSRI) have described the atomic-level workings of "microRNA" molecules, which control the expression of genes in all animals and plants.

Blocking a fork in the road to DNA replication

Oct 30, 2014

A team of Whitehead Institute scientists has discovered the surprising manner in which an enigmatic protein known as SUUR acts to control gene copy number during DNA replication. It's a finding that could shed new light on ...

Cell division, minus the cells

Oct 30, 2014

(Phys.org) —The process of cell division is central to life. The last stage, when two daughter cells split from each other, has fascinated scientists since the dawn of cell biology in the Victorian era. ...

A new method simplifies the analysis of RNA structure

Oct 30, 2014

To understand the function of an RNA molecule, similar to the better-known DNA and vital for cell metabolism, we need to know its three-dimensional structure. Unfortunately, establishing the shape of an RNA ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.