Distinct antibiotic treatment regimens differentially affect colonization resistance against multi-drug resistant Pseudomonas aeruginosa in mice

Besides its live-saving properties, antibiotic treatment affects the commensal microbiota facilitating colonization with potentially harmful microorganisms. Here we tested how commonly applied antibiotics induced gut microbiota changes and predisposed to intestinal carriage of multi-drug resistant Pseudomonas aeruginosa (MDR Psae) upon exposure. Therefore, mice received either vancomycin, ciprofloxacin, ampicillin plus sulbactam (A/S) or no antibiotics via the drinking water and were perorally challenged with a clinical MDR Psae isolate after antibiotic withdrawal. Whereas 100% of A/S and 55% of ciprofloxacin pretreated mice harbored Psae in their feces seven days post-challenge, intestinal Psae carriage rates were 20.0% and 26.3% in vancomycin pretreated and untreated mice, respectively. Microbiota analyses revealed that immediately before MDR Psae challenge, A/S pretreated mice displayed the lowest total bacterial, lactobacilli and Clostridium leptum fecal loads compared to other cohorts. Seven days following Psae exposure, however, higher numbers of apoptotic colonic epithelial cells were observed in A/S pretreated versus untreated mice that were accompanied by more enhanced innate and adaptive immune cell responses and nitric oxide secretion in colonic and ileal biopsies in the former versus the latter. In conclusion, distinct gut microbiota shifts following A/S pretreatment facilitate pronounced intestinal MDR Psae colonization and pro-inflammatory immune responses upon oral exposure.