Achromobacter xylosoxidans isolates exhibit genome diversity, variable virulence, high levels of antibiotic resistance and potential intrahost evolution.

Abstract

2. AbstractAchromobacter xylosoxidans is an emerging pathogen characterized by high levels of antibiotic resistance and increasing infection rates worldwide. This motile, opportunistic pathogen is widely distributed in the environment and can cause various infections, including pneumonia, bacteremia, endocarditis, meningitis, and others. In this study, we analyzed the population structure, antibiotic resistance profiles, and virulence factors of over 200 publicly available genomes. Core genome analysis revealed that A. xylosoxidans is highly adaptable, possessing a relatively small core genome. Antibiotic susceptibility testing of isolates from the United States revealed high resistance to multiple antibiotics. Our data show that imipenem/relebactam (IMR) is as effective against A. xylosoxidans as imipenem (IMI) alone, indicating that relebactam does not inhibit {beta}-lactamase activity in Achromobacter. The species features multiple secretion systems, including the Type III secretion system (T3SS) of the YscN family, which is similar to those found in Bordetella pertussis and Pseudomonas aeruginosa. Isolates collected from the same patients showed changes in cytotoxicity, flagella motility, biofilm and antibiotic resistance suggesting its dynamic adaptation to host environment. Intra-host evolved isolates, NIH-010, NIH-016 and NIH-018 demonstrated the loss of flagellar motility and variable cytotoxicity while exhibiting increased antibiotic resistance and enhanced biofilm formation. Sequence analysis suggests that NIH-016-3 has tyrosine to histidine mutation at position 330 near the FlhF Guanosine triphosphate (GTP)-binding domain that may affect flagellar assembly. Interestingly, virulence assays showed significant variation in the ability of different A. xylosoxidans isolates to induce cell death in in vitro models, suggesting its dynamic adaptation to host environment. 3. ImportanceThis study provides a comprehensive examination of Achromobacter xylosoxidans, an emerging pathogen of global concern due to its high antibiotic resistance and increasing clinical relevance. By analyzing over 200 genomes, we offer critical insights into the population structure, resistance mechanisms, and virulence factors of this species. The identification of a small core genome underscores its potential for genomic plasticity. The existence of multiple secretion systems highlights the great capacity of A. xylosoxidans as a pathogen. Variations in virulence among A. xylosoxidans isolates indicate the complexity of this pathogen underscoring the need for further studies on its virulence mechanisms. Evolution within the host includes the loss of motility-associated systems and enhanced antibiotic resistance and biofilm formation. This work showed that A. xylosoxidans are resistant to relebactam when combined with imipenem a combination effective in other bacteria. These findings emphasize the urgent need for targeted therapeutic strategies to combat this opportunistic pathogen.