Killing Biofilms

Microbes in a Biofilm are Harder to Kill than Microbes in Isolation

Another final characteristic of biofilms that we explore in this section—one that we have hinted at numerous times in this module—is that the microorganisms in a biofilm are much less susceptible to antimicrobial agents (chemicals designed to kill those microorganisms) than are the same microorganisms found in a planktonic state. Many studies have shown that the multicellular construction of biofilms affords protection for the cells that are part of these biofilms. This protection is the result of intrinsic shifts in the way these cells behave (through different genetic expression as described in subsection 2 above) once they attach to surfaces and begin to form biofilms. Some of the hypothesized mechanisms of protection from antimicrobial agents are pictured in the diagram below.

A. Free-floating cells utilize nutrients, but do not have sufficient metabolic activity to deplete substrates from the neighborhood of the cells.

In contrast, the collective metabolic activity of groups of cells in the biofilm leads to substrate concentration gradients and localized chemical microenvironments. Reduced metabolic activity may result in less susceptibility to antimicrobials.

B. Free-floating cells carry the genetic code for numerous protective stress responses. Planktonic cells, however, are readily overwhelmed by a strong antimicrobial challenge. These cells die before stress responses can be activated.

In contrast, stress responses are effectively implemented in some of the cells in a biofilm at the expense of other cells which are sacrificed.

A
B
C
D

C. Free-floating cells neutralize the antimicrobial agent. The capacity of a lone cell, however, is insufficient to draw down the antimicrobial concentration in the neighborhood of the cell.

In contrast, the collective neutralizing power of groups of cells leads to slow or incomplete penetration of the antimicrobial in the biofilm.

D. Free-floating cells spawn protected persister cells. But under permissive growth conditions in a planktonic culture, persisters rapidly revert to a susceptible state.

In contrast, persister cells accumulate in biofilms because they revert less readily and are physically retained by the biofilm matrix.