Scouting for novel bacteria

Few things are so mys­te­rious as bac­teria. Indeed, the Great Plate Anomaly has baf­fled micro­bial biol­o­gists for more than a cen­tury: While mil­lions of bac­te­rial species pop­u­late the globe, only about one-​​tenth of a per­cent are cul­tivable in the lab.

The rest have long been con­sid­ered “uncul­tivable,” but North­eastern biology pro­fessor Slava Epstein thinks otherwise.

In two papers released ear­lier this week in the journal Applied and Envi­ron­mental Micro­bi­ology, Epstein pro­poses a new “scout model” as a solu­tion to the Great Plate Anomaly. The model sug­gests that an evo­lu­tionary defense mech­a­nism ran­domly drives indi­vidual bac­teria into and out of dor­mancy. This cre­ates a pool of inac­tive cells that do not grow and remain essen­tially invis­ible, and are thus ignored.

This “dark matter,” as Epstein calls it, is the bac­te­rial insur­ance policy: Envi­ron­mental or antibi­otic chal­lenges cannot kill dor­mant cells. A tiny frac­tion will ran­domly wake up into activity, unwit­tingly “scouting” the envi­ron­ment for the rest of the pop­u­la­tion. If con­di­tions are chal­lenging, these pio­neers will die, to be replaced by a new gen­er­a­tion of sim­i­larly awak­ening scouts. How­ever, if con­di­tions are good, they will grow, form a new pop­u­la­tion and may even send mol­e­c­ular invi­ta­tions out for others to wake up and join the party.

“What I’m saying is many so-​​called ‘uncul­tivable’ species are per­fectly cul­tivable, and there may be nothing unusual about them. It’s just that, number one, they are rare and, number two, the over­whelming majority of cells of any species in nature are dor­mant at any given time. They wake up ran­domly at low frequency.”

Slava Epstein with lab member Maria Sizova.

If Epstein is cor­rect, then new cul­ti­va­tion methods and stronger efforts could open the door to an influx of novel species. Since bac­teria bring with them mol­e­cules spe­cial­ized in killing their neigh­bors, the scout model could also reopen the field of antibi­otic dis­covery, which had its last break­through in the 1980s.

Epstein’s model ques­tions the long-​​held assump­tion that micro­bial growth is time-​​dependent. That is, some species take longer to grow than others, and since typ­ical lab cul­tures only last a short period, the longer-​​term bac­teria never get a chance to grow.

Epstein’s lab hypoth­e­sized that if this were the case, then long-​​term cul­ti­va­tion should at first pro­duce the bac­teria that com­monly grow in the lab, like E. coli, fol­lowed by more novel species later on. But when the team let a bac­te­rial sample cul­ti­vate for a year and a half (one of the longest cul­tures ever per­formed), researchers found the same fre­quency of novel bac­teria throughout the time period.

If the scout model is cor­rect, then the prob­a­bility of finding a novel species is the same regard­less of incu­ba­tion time: If a sample con­tains a mil­lion cells of one pop­u­la­tion and only 10 cells of another, then the chances of “cap­turing” an active scout out of the latter are minimal.

“You see?” he said. “Then the dis­covery of new species will be a random event. It will be a game of num­bers.”