Nonmultiplying Bacteria are Profoundly Tolerant to Antibiotics
Bacteria survive treatments with antimicrobial agents; they achieve this in two ways. Firstly, bacteria quickly become tolerant to these agents. This tolerance is temporary, reversible, and associated with slowing of the multiplication rate. Secondly, bac
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Contents 1
Nonmultiplying Bacteria and Persisters . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.1 Nonmultiplying Stationary-Phase Bacteria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.2 Biofilms: Another Form of Nonmultiplying Bacteria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.3 Persisters . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.4 Dormant Bacteria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Clinical Importance of Persistent Bacteria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Persistent M. tuberculosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1 Different Populations of M. tuberculosis in Human Lesions . . . . . . . . . . . . . . . . . . . . . . . 3.2 Dormant M. tuberculosis in Animal Models . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.3 Subpopulations of Nonmultiplying M. tuberculosis In Vitro . . . . . . . . . . . . . . . . . . . . . . . 4 Antibiotics Kill Nonmultiplying Bacteria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1 Bactericidal and Sterilizing Antibiotics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.2 Antimicrobials Targeting Cell Membrane and Cell Wall . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.3 Antipersister Formation and Waking up Dormancy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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Abstract Bacteria survive treatments with antimicrobial agents; they achieve this in two ways. Firstly, bacteria quickly become tolerant to these agents. This tolerance is temporary, reversible, and associated with slowing of the multiplication rate. Secondly, bacteria can undergo genetic mutations leading to permanent clonal resistance to antimicrobial agents. In patients with infections, nonmultiplying bacteria, some of which may be viable but nonculturable, exist side by side with multiplying bacteria. Current antibiotics capable of killing actively multiplying bacteria have very limited or no effect against nonmultiplying bacteria. Treatment
Y. Hu (*) • A. Coates Medical Microbiology, Division of Clinical Sciences, Centre for Infection, St George’s U
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