Staphylococcus aureus is a bacterium that colonizes the skin (and, often, the noses) of about one in three people, mostly just hanging out without causing symptoms. But when it breaches the skin barrier, it becomes a formidable pathogen.
S. aureus not only accounts for the majority of skin and soft-tissue infections in the U.S. and Europe, but can spread to deeper tissues leading to dangerous invasive infections in virtually every organ including the lungs, heart valves, and bones. These complications cause an estimated 11,000 deaths in the U.S. annually.
Making matters worse, antibiotic-resistant strains of S. aureus are becoming increasingly prevalent and even more difficult and costly to treat. All of which makes it crucial to understand the factors that control the bug’s virulence: What turns a common colonizer into a pathogen?
The answers that typically spring to mind involve molecules the pathogen produces that enable damage to cells of the host organism. Certainly S. aureus is no slouch in that arena. Prominent among the many virulence factors it produces, one called α-toxin aggregates on host cell surfaces to form pores that injure the cells’ outer membranes, often killing the cells.
But it turns out that forming pores appears not to be enough, by itself, for lethal host-cell injury. In a study published in Proceedings of the National Academy of Sciences, a team directed by Stanford microbe sleuths Manuel Amieva, MD, PhD, and Jan Carette, PhD, identified several hitherto-unsuspected molecules produced within host cells themselves that determine whether the cells live or die after α-toxin-induced pore formation.
The newly identified molecules are components of adherens junctions, complicated cellular structures that knit cells together forming a barrier to the penetration of, or leakage out of or into, tissues such as skin and the linings of our internal organs.
The Stanford investigators focused on one obscure molecular member of the adherens junctions that proved to be key to cells’ susceptibility to S. aureus: a protein named PLEKHA7, found in all cells that form cell-cell junctions. Oddly, unlike other molecules in adherens junctions, PLEKHA7 appears relatively unessential. Cells, and even mice, lacking PLEKHA7 can be artificially engineered and appear normal.
Genetically engineered PLEKHA7-lacking cells and mice proved better able to survive injury from the α-toxin as well as infection with antibiotic-resistant S. aureus strains. Similarly, mice lacking PLEKHA7 still became sick after S. aureus infection, but survived and healed faster, while most mice with PLEKHA7 died. Mice lacking PLEKHA7 not only better healed S. aureus skin infections but also survived S. aureus pneumonia, a major clinical manifestation of human S. aureus infection.
The unexpected observation that a seemingly inconsequential protein, PLEKHA7, plays a starring role in whether cells survive a S. aureus infection may lead to new drugs that, by temporarily knocking out PLEKHA7’s activity, protect us from the ravages of S. aureus.
As Cassius, in Shakespeare’s towering tragedy Julius Caesar, might have put it, “The fault, dear Brutus, is not in Staph aureus, but in our cells.”
Previously: Staphylococcus aureus holes up in upper nasal cavity, study shows, Ulcer-causing bacteria manipulate stomach stem cells to their own ends and Guts and glory: Growing intestinal tissue in a lab dish
Photo by Dawn Endico