Abstract
Extraintestinal pathogenic Escherichia coli (ExPEC) causes a variety of acute infections in its hosts, and multidrug-resistant strains present significant challenges to public health and animal husbandry. Therefore, it is necessary to explore new drug targets to control E. coli epidemics. Previous studies have reported that ppk mutants of Burkholderia pseudomallei and Mycobacterium tuberculosis are more susceptible than the wild types (WTs) to stress. Therefore, we investigated the stress response to antibiotics mediated by polyphosphate kinase (PPK) in ExPEC strain PCN033. We observed that planktonic cells of a ppk knockout strain (Δppk) were more susceptible to antibiotics than was WT. However, biofilm-grown Δppk cells showed similar susceptibility to that of the WT and were more tolerant than the planktonic cells. During the planktonic lifestyle, the expression of genes involved in antibiotic tolerance (including resistance-conferring genes, and antibiotic influx, and efflux genes) did not change in the Δppk mutant without antibiotic treatment. However, the resistance-conferring gene bla and efflux genes were upregulated more in the WT than in the Δppk mutant by treatment with tazobactam. After treatment with gentamycin, the efflux genes and influx genes were upregulated and downregulated, respectively, more in the WT than in the Δppk mutant. The expression of genes involved in biofilm regulation also changed after treatment with tazobactam or gentamycin, and which is consistent with the results of the biofilm formation. Together, these observations indicate that PPK is important for the antibiotic stress response during the planktonic growth of ExPEC and might be a potential drug target in bacteria.
Highlights
Extraintestinal pathogenic Escherichia coli (ExPEC) is a major cause of urinary tract infections in women, abdominal sepsis, and septicemia in elderly or immunocompromised individuals, and meningitis in newborns, with high morbidity and mortality (Gaschignard et al, 2011; Weston et al, 2011; Mellata, 2013)
Because pathogenic E. coli mainly causes acute infections in its planktonic growth mode (Li et al, 2014), we initially investigated the role of polyphosphate kinase (PPK) in the antibiotic resistance of ExPEC in the planktonic growth mode
We investigated in detail its susceptibility to different types of antibiotics, mediated by PPK, in E. coli
Summary
Extraintestinal pathogenic Escherichia coli (ExPEC) is a major cause of urinary tract infections in women, abdominal sepsis, and septicemia in elderly or immunocompromised individuals, and meningitis in newborns, with high morbidity and mortality (Gaschignard et al, 2011; Weston et al, 2011; Mellata, 2013). ExPEC strains commonly colonize domestic animals, such as pigs, chickens, and cattle, causing significant losses in animal husbandry and threating human health (Girardeau et al, 2003; Johnson et al, 2005; Bergeron et al, 2012). The frequency of ExPEC isolated from pigs increased between 2004 and 2007 from 3.1 to 14.6% (Tan et al, 2012). The emergence of multidrug-resistant strains has significantly hindered the prevention and control of ExPEC epidemics (Sedláková et al, 2014; Sidrach-Cardona et al, 2014). It is urgent that we identify new drug targets to control these increasing E. coli outbreaks
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