Journal
ANTIBIOTICS-BASEL
Volume 10, Issue 9, Pages -Publisher
MDPI
DOI: 10.3390/antibiotics10091033
Keywords
Enterobacterales; keratitis; infection; cornea; bacteria; stress response system; antibiotic
Categories
Funding
- Research to Prevent Blindness
- Eye and Ear Foundation of Pittsburgh
- National Institute of Health [P30EY08098, R01EY027331]
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The Rcs phosphorelay is a bacterial stress response system that influences multiple pathogenic phenotypes and drug tolerance. Different classes of antibiotics can activate the Rcs system to varying degrees, regardless of the susceptibility status of the bacterium.
The Rcs phosphorelay is a bacterial stress response system that responds to envelope stresses and in turn controls several virulence-associated pathways, including capsule, flagella, and toxin biosynthesis, of numerous bacterial species. The Rcs system also affects antibiotic tolerance, biofilm formation, and horizontal gene transfer. The Rcs system of the ocular bacterial pathogen Serratia marcescens was recently demonstrated to influence ocular pathogenesis in a rabbit model of keratitis, with Rcs-defective mutants causing greater pathology and Rcs-activated strains demonstrating reduced inflammation. The Rcs system is activated by a variety of insults, including beta-lactam antibiotics and polymyxin B. In this study, we developed three luminescence-based transcriptional reporters for Rcs system activity and used them to test whether antibiotics used for empiric treatment of ocular infections influence Rcs system activity in a keratitis isolate of S. marcescens. These included antibiotics to which the bacteria were susceptible and resistant. Results indicate that cefazolin, ceftazidime, polymyxin B, and vancomycin activate the Rcs system to varying degrees in an RcsB-dependent manner, whereas ciprofloxacin and tobramycin activated the promoter fusions, but in an Rcs-independent manner. Although minimum inhibitory concentration (MIC) analysis demonstrated resistance of the test bacteria to polymyxin B and vancomycin, the Rcs system was activated by sub-inhibitory concentrations of these antibiotics. Together, these data indicate that a bacterial stress system that influences numerous pathogenic phenotypes and drug-tolerance is influenced by different classes of antibiotics despite the susceptibility status of the bacterium.
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