The use of minimum selectable concentrations (MSCs) for determining the selection of antimicrobial resistant bacteria
The use of minimum selectable concentrations (MSCs) for determining the selection of antimicrobial resistant bacteria
Sadia Khan 0 1
● Tara K. Beattie 0 1
● Charles W. Knapp 0 1
0 Department of Environmental Engineering, NED University of Engineering and Technology , University Road, Karachi 75270 , Pakistan
1 Department of Civil and Environmental Engineering, University of Strathclyde , James Weir Building, 75 Montrose Street, Glasgow, Scotland G1 1XJ , UK
The use of antimicrobial compounds is indispensable in many industries, especially drinking water production, to eradicate microorganisms. However, bacterial growth is not unusual in the presence of disinfectant concentrations that would be typically lethal, as bacterial populations can develop resistance. The common metric of population resistance has been based on the Minimum Inhibitory Concentration (MIC), which is based on bacteria lethality. However, sub-lethal concentrations may also select for resistant bacteria due to the differences in bacterial growth rates. This study determined the Minimal Selective Concentrations (MSCs) of bacterial populations exposed to free chlorine and monochloramine, representing a metric that possibly better reflects the selective pressures occurring at lower disinfectant levels than MIC. Pairs of phylogenetically similar bacteria were challenged to a range of concentrations of disinfectants. The MSCs of free chlorine and monochloramine were found to range between 0.021 and 0.39 mg L−1, which were concentrations 1/250 to 1/5 than the MICs of susceptible bacteria (MICsusc). This study indicates that sub-lethal concentrations of disinfectants could result in the selection of resistant bacterial populations, and MSCs would be a more sensitive indicator of selective pressure, especially in environmental systems.
Minimal selective concentration (MSC) ●; Minimum inhibitory concentration (MIC) ● Disinfectant ●; Drinking water
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Overuse and misuse of antimicrobials during the last
century have created issues related to the emergence and
enrichment of resistant bacteria (Carlet et al. 2012),
especially antimicrobial resistant pathogens that could
contaminate water supply systems and survive their disinfection
(Khan et al. 2016b; Xu et al. 2016). Almost every antibiotic
has bacteria that have shown resistance to it (Kummerer
2009b), and these bacteria have been found in water,
sanitation and agricultural industries (Kummerer 2009a; Li et al.
2016) and could be attributed to selective pressures exerted
by environmental concentrations of antimicrobials (Tello
et al. 2012; Sandegren 2014). There are concerns that these
selective pressure will increase the evolution and spread of
antibiotic resistant pathogens (Baquero et al. 1998;
Bengtsson-Palme and Larsson 2016), and that the driving
forces behind the development and selection of resistance
are not fully understood due to the complexity of the
interactions between bacteria, antimicrobials and
environment.
Minimum Inhibitory Concentration (MIC) has been used
widely to understand the susceptibility and resistance of
bacteria to antimicrobials; this was derived in the clinical
setting to represent population lethality. Basically, resistant
populations become selected at environmental
concentrations higher than the MIC of susceptible bacteria (MICsusc),
while sub-MIC levels allow the continued growth of both
MSC
Fig. 1 Schematic representation of growth rates as a function of
antibiotic concentrations. MICsusc (blue line) minimum inhibitory
concentration for susceptible strain, MICres (red line) minimum
inhibitory concentration for resistant strain, MSC minimum selective
concentration. Adapted from Gullberg et al. (2011) and Sandegren
(2014) (color figure online)
susceptible and resistant genotypes (Andersson and Hughes
2014, Bengtsson-Palme et al. 2014a). Traditionally, it has
been presumed that resistant bacteria have a competitive
advantage at concentrations greater than the MIC
(Sandegren 2014).
However, concentrations below the MIC could favour
highly resistant bacteria (Li et al. 2016). As such,
microbiologists have defined minimum selective concentrations
(MSC), which represents the lowest concentration of
antimicrobials that gives the resistant strains a competitive
advantage based on growth rates (Fig. 1) (Andersson and
Hughes 2014). This better reflects enrichment possibilities
of resistant bacteria in environments where low levels of
antimicrobial are present, for example in soils and drinking
water sources (Baquero et al. 1998, 2008; Fram and Belitz
2011; Jiang et al. 2013; Khan et al. 2013).
The MSC represents the point at which the benefit in
growth exceeds the cost (fitness cost) of carrying the
resistance trait vs. a non-resistant strain (Gullberg et al.
2011), and as such, there is a competitive advantage for
having the resistance trait at concentrations greater than
MSC (Sandegren 2014). The difference in fitness between
susceptible and resistant organi (...truncated)