Nonmultiplying Bacteria are Profoundly Tolerant to Antibiotics

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 of such infections requires a regimen of multiple antimicrobial agents in order to control nonmultiplying persistent bacteria. This is especially important in tuberculosis where there is co-existence of slowly multiplying tolerant bacteria with fast growing sensitive organisms. For this reason, a prolonged length of chemotherapy, lasting 6 months, is necessary to achieve cure. This long duration of treatment is due to the slow, inadequate effect of antibiotics on nonmultiplying persistent bacteria. Similar problems with eradication of persistent bacteria are evident in the treatment of biofilms. These bacteria serve as a pool for recurrent infections. Extended courses of antibiotics increase the likelihood of genetic resistance, raise the cost of treatments, and lead to more side effects.

Identification of 1-((2,4-Dichlorophenethyl)Amino)-3-Phenoxypropan-2-ol, a Novel Antibacterial Compound Active against Persisters of Pseudomonas aeruginosa

“…Experiments were further focused on stationary-phase cultures, since the absence of active growth, a higher persister fraction, and nutritional starvation result in a more pronounced antibiotic tolerance and, partly due to the similarities to biofilms, increased clinical relevance (13,41). Other antipersister molecules primarily aimed at targeting nonmultiplying cells have been described for Mycobacterium tuberculosis (42) and S. aureus (43).…”

Current Perspectives on Viable but Non-culturable State in Foodborne Pathogens

“…During food pasteurization and preservation processes, certain bacterial cells can be induced to enter the VBNC state (Zhao F. et al, 2013; Kramer and Muranyi, 2014). In general, VBNC cells are resistant to multiple antimicrobials, which may cause treatment failure at times (Hu and Coates, 2012). In fact, a recent study found that foods subjected to antimicrobial treatment harbored considerable numbers of VBNC cells (Anvarian et al, 2016).…”

Current Perspectives on Viable but Non-Culturable (VBNC) Pathogenic Bacteria

“…During the process of infection and in the course of treatment regimens, certain bacterial cells can transfer into the VBNC state. In this state, the bacteria are generally resistant to multiple antimicrobials and this may cause treatment failure at times (82). A good example of this phenomenon is the drug resistance of tuberculosis.…”

“…A good example of this phenomenon is the drug resistance of tuberculosis. The non-culturable Mycobacterium tuberculosis is multi-drug resistance and may prolong the infection and chemotherapy for long time (82). …”