Within-patient genomic evolution of invasive Campylobacter jejuni associated with bloodstream persistence and antibiotic resistance

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Campylobacter jejuni is a leading cause of bacterial gastroenteritis, and fluoroquinolone-resistant strains represent a major public health concern. Still, C. jejuni can also cause invasive disease, particularly in immunocompromised individuals, highlighting the need to elucidate the adaptive mechanisms behind bloodstream invasion and persistence. This study aimed to characterize the within-patient genomic evolution of an invasive C. jejuni strain. Whole-genome sequencing was performed on same-patient isolates from stool (n = 1) and blood (n = 2), followed by in-depth genomic comparisons and antimicrobial susceptibility testing. Here we show that rapid within-patient microevolution is driven by amino acid substitutions and small inactivating indels. Most mutated loci have predicted or reported functions related to motility (including flagella- and energy taxis/chemotaxis-associated proteins), adherence, cell shape/envelope organization and host interactions (e.g., immune evasion and resistance to blood environment). All isolates are resistant to ciprofloxacin (MIC = 16 mg/L) due to the canonical GyrA Thr86Ile substitution. After about one month of infection (including a 21-day ciprofloxacin treatment), ciprofloxacin MIC increased to 128 mg/L and a newly acquired resistance to moxifloxacin (MIC > 32 mg/L) was observed. This expanded resistance profile correlates with the emergence of the GyrA Asp90Gly substitution (previously unreported in C. jejuni) and a 1-bp deletion in the cmeABC promoter region (previously demonstrated to increase efflux pump expression). Dynamic phase variation of several loci was also observed during bloodstream persistence, including ON-phase switching of the cell invasion protein A (CipA). These genomic findings provide insight into within-host population shifts and the emergence of antibiotic-resistant clones, contributing to better understanding the dynamics associated with C. jejuni bloodstream invasion and persistence. Campylobacter jejuni (C. jejuni) is a species of bacteria that commonly causes foodborne illness. In rare cases, especially in people with weakened immune systems, it can spread from the gut into the bloodstream causing severe infection. We wanted to understand how this bacterium changes inside the body during this type of infection and how it becomes more resistant to antibiotics. We compared the complete DNA of bacteria collected from the stool and blood of the same patient over about one month, together with laboratory tests of antibiotic susceptibility. We found that the bacterium rapidly accumulated genetic changes potentially linked to survival in the bloodstream and developed increased resistance to important antibiotics during treatment. These findings improve our understanding of how C. jejuni adapts during invasive infection and may help improve diagnosis, treatment, and future surveillance of antibiotic-resistant strains. Borges et al. investigate the within-host evolution of an invasive Campylobacter jejuni strain using stool and blood isolates collected from a patient over one month. Observed genetic changes may be associated with bloodstream persistence and the emergence of increased antimicrobial resistance, suggesting their possible role in adaptation and invasive disease.

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