Abstract
When faced with nutritional deprivation, bacteria undergo a range of metabolic, regulatory, and biosynthetic changes. Those adjustments, which can be specific or independent of the missing nutrient, often alter bacterial tolerance to antibiotics. Here, using fluoroquinolones, we quantified Escherichia coli persister levels in cultures experiencing starvation from a lack of carbon (C), nitrogen (N), phosphorous (P), or magnesium (Mg2+). Interestingly, persister levels varied significantly based on the type of starvation as well as fluoroquinolone used with N-starved populations exhibiting the highest persistence to levofloxacin, and P-starved populations exhibiting the highest persistence to moxifloxacin. However, regardless of the type of starvation or fluoroquinolone used, DNA repair was required by persisters, with ∆recA and ∆recB uniformly exhibiting the lowest persistence of the mutants assayed. These results suggest that while the type of starvation and fluoroquinolone will modulate the level of persistence, the importance of homologous recombination is consistently observed, which provides further support for efforts to target homologous recombination for anti-persister purposes.
Highlights
Nutrient limitation is a stress that bacteria can experience in a host [1,2,3]
FQs are some of the few antibiotics that retain activity against non-growing bacteria
FQs are some of the few antibiotics that retain activity against non-growing bacte[10,23,24], and their bactericidal activity derives from their binding to type II topoisomerria [10,23,24], and their bactericidal activity derives from their binding to type II topoisoases (DNA gyrase and topoisomerase IV in E. coli), which allows DNA cleavage but premerases (DNA gyrase and topoisomerase IV in E. coli), which allows DNA cleavage but vents ligation [26,56]
Summary
Nutrient limitation is a stress that bacteria can experience in a host [1,2,3]. For example, in the urinary tract, which is a common site of infections [4], urine constitutes a poor growth medium, since it lacks glucose, contains high concentrations of urea, and low levels of peptides and amino acids [1,5]. CO2 generation, and O2 consumption differ between carbon (C)-, N-, and phosphate (P)-starved cultures [20], whereas glucose consumption varies between N-, P-, and Mg2+ -starved populations, with Mg2+ -starved cultures catabolizing glucose at the highest rate [16]. With such metabolic and regulatory differences, microorganisms10020286. In a study with nitrofurantoin, when stationary-phase bacteria were resuspended in saline, only C-supplied bacteria became sensitive to the antibiotic, whereas N-, P-, and Mg2+ -supplied bacteria remained completely tolerant [22] These studies suggest that while growth inhibition in general increases the tolerances of bacteria to antibiotics, it may not do so in a uniform fashion
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