Enhanced in vivo fitness of fluoroquinolone-resistant Campylobacter jejuni in the absence of antibiotic selection pressure

Abstract

Campylobacter jejuni, a major foodborne human pathogen, has become increasingly resistant to fluoroquinolone (FQ) antimicrobials. By using clonally related isolates and genetically defined mutants, we determined the fitness of FQ-resistant Campylobacter in chicken (a natural host and a major reservoir for C. jejuni) in the absence of antibiotic selection pressure. When monoinoculated into the host, FQ-resistant and FQ-susceptible Campylobacter displayed similar levels of colonization and persistence in the absence of FQ antimicrobials. The prolonged colonization in chickens did not result in loss of the FQ resistance and the resistance-conferring point mutation (C257 3 T) in the gyrA gene. Strikingly, when coinoculated into chickens, the FQ-resistant Campylobacter isolates outcompeted the majority of the FQ-susceptible strains, indicating that the resistant Campylobacter was biologically fit in the chicken host. The fitness advantage was not due to compensatory mutations in the genes targeted by FQ and was linked directly to the single point mutation in gyrA, which confers on Campylobacter a high-level resistance to FQ antimicrobials. In certain genetic backgrounds, the same point mutation entailed a biological cost on Campylobacter, as evidenced by its inability to compete with the FQ-susceptible Campylobacter. These findings provide a previously undescribed demonstration of the profound effect of a resistance-conferring point mutation in gyrA on the fitness of a major foodborne pathogen in its natural host and suggest that the rapid emergence of FQ-resistant Campylobacter on a worldwide scale may be attributable partly to the enhanced fitness of the FQ-resistant isolates.colonization ͉ gyrA mutation ͉ poultry A ntimicrobial resistance in bacterial pathogens has become a serious threat to public health. There is a general notion that the acquisition of drug resistance, particularly the resistance mediated by chromosomal mutations, entails a biological cost for pathogens, resulting in reduced fitness in the absence of antibiotic selection pressure (1, 2). However, evidence has accumulated that in vivo-selected or clinically derived isolates may develop compensatory mutations that reduce the fitness cost associated with antimicrobial resistance (3-7). Different environments (in vitro vs. in vivo) may select for different compensatory mutations and varied levels of restoration of fitness (8). Even without compensatory mutations, drug-resistant mutants may show little or no fitness cost (9). One important finding revealed by previous studies is that clinically derived drugresistant isolates display diverse fitness changes, with some showing a biological cost and others showing no cost or even enhanced fitness (4, 10). The retention of ecological fitness in resistant pathogens creates a significant barrier for the elimination of resistant organisms by natural selection.Campylobacter jejuni, a Gram-negative microaerobic bacterium, is a common causative agent of human enterocolitis (11). For antibiotic treatment of ca...

Molecular mechanisms of quinolone, macrolide, and tetracycline resistance amongCampylobacterisolates from initial stages of broiler production

“…These data are consistent with published data (Piddock et al, 2003;Luo et al, 2005). This mutation is the most prevalent in clinical and veterinary isolates, among other described mutations (Thr86Ala, Thr86Lys, Ala87Pro, Asp90His, Asp90Tyr, etc.)…”

“…For the investigation of quinolone resistance, a region of 1081 base pairs (bp) from the gyrA gene including the QRDR region (210 bp) was amplified using the primers GyrAF1 (5′-CAACTGGTTCTAGCCTTTTG-3′) and GyrAR1 (5′-AATTTCACTCATAGCCTCACG-3′), as described previously (Luo et al, 2005). Another PCR was carried out to determine the presence of the tetO gene responsible for tetracycline resistance in Campylobacter spp.…”

High level of ciprofloxacin resistance and its molecular background among Campylobacter jejuni strains isolated in the United Arab Emirates

“…In humans, fluoroquinolone-resistant strains are shed longer than sensitive isolates (Nelson et al, 2004;Engberg et al, 2004), and they have been reported to out-compete their sensitive counterparts, at least in certain genetic backgrounds, when colonizing poultry, i.e. the natural reservoir of the pathogen (Luo et al, 2005). All these findings underscore the necessity for close monitoring of the incidence and spread of fluoroquinolone-resistant clones of C. jejuni.…”

The contribution of PmrAB to the virulence of a clinical isolate ofEscherichia coli

“…[1][2][3][4] The three related transcription factors, MarA, Rob, and SoxS, act in both individual and redundant manners to affect antibiotic resistance and virulence of Escherichia coli, through known and unknown mechanisms. 5,6 These three transcription factors play a key role in the persistence of E. coli in a murine kidney infection model, where deletion of all three genes significantly decreases the bacterial load in the kidney after three days of successful colonization.…”