Introduction Neisseria gonorrhoeae resistance to extended-spectrum cephalosporins as well as treatment failures with ESCs has been increasingly reported in many countries globally. These increasing trends together with the limitation of drugs of choice lead gonorrhoea to become a global health concern. Herein, we aimed to reveal more understanding on the physiological response of gonococci to ESCs using proteomic approach.

Methods N. gonorrhoeae reference strain was grown with or without a subinhibitory dose of ESCs. Protein expression was determined by 2-dimensional gel electrophoresis in conjunction with MALDI-TOF/TOF MS analysis.

Results In total, 14 and 13 proteins were significantly altered expression following exposure to ceftriaxone and cefixime, respectively. Most of expressed proteins shared a similar expression pattern in response to ceftriaxone and cefixime reflecting similarities in antibiotic mechanisms. ESC antibiotics triggered proteins in a variety of functions, such as membrane protein, transport system, energy metabolism, and stress response, which would help gonococci to survive under drug stress. Interestingly, the subinhibitory dose of ESCs also triggered the expression of gonococcal virulence factors (e.g. azurin and peptidyl-prolyl isomerase), which might be an adaptation mechanism of gonococci in ESC stress and also affect the outcome of gonococcal infection.

Conclusion The present work might provide new insights into physiological adaptive networks of gonococci to antimicrobial agents and more understanding toward the mechanism of action, which subsequently may benefit for the further drug discovery of new antimicrobials to combat with resistant gonococci.