The drug tolerant persisters of Riemerella anatipestifer can be eradicated by a combination of two or three antibiotics

Abstract

BackgroundRiemerella anatipestifer (RA), the causative agent of duck infectious serositis, leads to high mortality in duck flocks and great economic losses in duck industry. Previous studies on RA are largely focused on its detection, virulence factors, serology, epidemiology as well as antibiotic resistance. Neither drug tolerant persisters nor the persister level under the treatment of antibiotics has been revealed. The persisters are non-growing or dormant cells within an isogenic bacterial population; they play important roles in recurrent infection and formation of drug resistant mutants. The aim of this study is to detect the drug tolerant persisters from the exponentially grown population of RA reference strain (RA 11845) or RA clinical isolate (RA TQ3), and address whether a single antibiotic or a combination of two or three antimicrobials can eradicate the persisters at respective maximum serum/plasma concentration (Cmax).ResultWith the concentration of a test antibiotic increased, a small fraction of cells in the exponentially grown culture of RA reference strain (RA 11845) or RA clinical isolate (RA TQ3) always survived, irrespective of treatment time, indicating the presence of drug tolerant presisters. A single antibiotic cannot eradicate the persisters of both RA strains at respective Cmax, except that the Cmax of ceftiofur wiped out the population of the reference strain (RA 11845). Besides, the clinical isolate RA TQ3 presented a higher tolerance to ceftiofur in comparison to that of the reference strain (RA 11845). Combination of any two or three antimicrobials eliminated the drug tolerant persisters of RA TQ3 completely at respective Cmax.ConclusionA sub-community of drug tolerant persisters was present in RA population. Persisters of RA TQ3 are single drug tolerant and not multidrug tolerant persisters.