Conceptual Model of Biofilm Antibiotic Tolerance That Integrates Phenomena of Diffusion, Metabolism, Gene Expression, and Physiology
Abstract
Bacteria in biofilms are protected from killing by antibiotics, and this reduced susceptibility contributes to the persistence of infections such as those in the cystic fibrosis lung and chronic wounds. A generalized conceptual model of biofilm antimicrobial tolerance with the following mechanistic steps is proposed: (i) establishment of concentration gradients in metabolic substrates and products; (ii) active biological responses to these changes in the local chemical microenvironment; (iii) entry of biofilm cells into a spectrum of states involving alternative metabolisms, stress responses, slow growth, cessation of growth, or dormancy (all prior to antibiotic treatment); (iv) adaptive responses to antibiotic exposure; and (v) reduced susceptibility of microbial cells to antimicrobial challenges in some of the physiological states accessed through these changes.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Nov 15, 2019
- Source ID
- 10.1128/jb.00307-19
Entities
People
- Anders Wallqvist
- Ben White
- Brian Bothner
- Francisco G. Vital-lopez
- Garth A. James
- Kerry S. Williamson
- Laura Boegli
- Michael J. Franklin
- Philip Stewart
- Steve Fisher
- Timothy Hamerly
Organizations
- Montana State University
- National Institute of General Medical Sciences
- United States Department of Defense